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  1. Cosine Directional Tuning of Theta Cell Burst Frequencies: Evidence for Spatial Coding by Oscillatory Interference

    PubMed Central

    Welday, Adam C.; Shlifer, I. Gary; Bloom, Matthew L.; Zhang, Kechen

    2011-01-01

    The rodent septohippocampal system contains “theta cells,” which burst rhythmically at 4–12 Hz, but the functional significance of this rhythm remains poorly understood (Buzsáki, 2006). Theta rhythm commonly modulates the spike trains of spatially tuned neurons such as place (O'Keefe and Dostrovsky, 1971), head direction (Tsanov et al., 2011a), grid (Hafting et al., 2005), and border cells (Savelli et al., 2008; Solstad et al., 2008). An “oscillatory interference” theory has hypothesized that some of these spatially tuned neurons may derive their positional firing from phase interference among theta oscillations with frequencies that are modulated by the speed and direction of translational movements (Burgess et al., 2005, 2007). This theory is supported by studies reporting modulation of theta frequency by movement speed (Rivas et al., 1996; Geisler et al., 2007; Jeewajee et al., 2008a), but modulation of theta frequency by movement direction has never been observed. Here we recorded theta cells from hippocampus, medial septum, and anterior thalamus of freely behaving rats. Theta cell burst frequencies varied as the cosine of the rat's movement direction, and this directional tuning was influenced by landmark cues, in agreement with predictions of the oscillatory interference theory. Computer simulations and mathematical analysis demonstrated how a postsynaptic neuron can detect location-dependent synchrony among inputs from such theta cells, and thereby mimic the spatial tuning properties of place, grid, or border cells. These results suggest that theta cells may serve a high-level computational function by encoding a basis set of oscillatory signals that interfere with one another to synthesize spatial memory representations. PMID:22072668

  2. Direct Evidence for Pitavastatin Induced Chromatin Structure Change in the KLF4 Gene in Endothelial Cells

    PubMed Central

    Kanki, Yasuharu; Kohro, Takahide; Li, Guoliang; Ohta, Yoshihiro; Kimura, Hiroshi; Kobayashi, Mika; Taguchi, Akashi; Tsutsumi, Shuichi; Iwanari, Hiroko; Yamamoto, Shogo; Aruga, Hirofumi; Dong, Shoulian; Stevens, Junko F.; Poh, Huay Mei; Yamamoto, Kazuki; Kawamura, Takeshi; Mimura, Imari; Suehiro, Jun-ichi; Sugiyama, Akira; Kaneki, Kiyomi; Shibata, Haruki; Yoshinaka, Yasunobu; Doi, Takeshi; Asanuma, Akimune; Tanabe, Sohei; Tanaka, Toshiya; Minami, Takashi; Hamakubo, Takao; Sakai, Juro; Nozaki, Naohito; Aburatani, Hiroyuki; Nangaku, Masaomi; Ruan, Xiaoan; Tanabe, Hideyuki; Ruan, Yijun; Ihara, Sigeo; Endo, Akira; Kodama, Tatsuhiko; Wada, Youichiro

    2014-01-01

    Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells. PMID:24797675

  3. A direct evidence of morphological degradation on a nanometer scale in polymer solar cells.

    PubMed

    Schaffer, Christoph J; Palumbiny, Claudia M; Niedermeier, Martin A; Jendrzejewski, Christian; Santoro, Gonzalo; Roth, Stephan V; Müller-Buschbaum, Peter

    2013-12-10

    In situ measurement of a polymer solar cell using micro grazing incidence small angle X-ray scattering (μGISAXS) and current-voltage tracking is demonstrated. While measuring electric characteristics under illumination, morphological changes are probed by μGISAXS. The X-ray beam (green) impinges on the photo active layer with a shallow angle and scatters on a 2d detector. Degradation is explained by the ongoing nanomorphological changes observed.

  4. Proneurotrophin-3 is a neuronal apoptotic ligand: evidence for retrograde-directed cell killing

    PubMed Central

    Yano, Hiroko; Torkin, Risa; Martin, Laura Andrés; Chao, Moses V.; Teng, Kenneth K.

    2010-01-01

    While mature neurotrophins are well-described trophic factors that elicit retrograde survival signaling, the precursor forms of neurotrophins (i.e., proneurotrophins) can function as high affinity apoptotic ligands for selected neural populations. An outstanding question is whether target-derived proneurotrophins might affect neuronal survival/death decisions through a retrograde transport mechanism. Since neurotrophin-3 (NT-3) is highly expressed in non-neural tissues that receive peripheral innervation, we investigated the localized actions of its precursor (proNT-3) on sympathetic neurons in the present study. Pharmacological inhibition of intracellular furin proteinase activity in 293T cells resulted in proNT-3 release instead of mature NT-3 while membrane depolarization in cerebellar granule neurons stimulated endogenous proNT-3 secretion, suggesting that proNT-3 is an inducible bona fide ligand in the nervous system. Our data also indicate that recombinant proNT-3 induced sympathetic neuron death that is p75NTR- and sortilin-dependent, with hallmark features of apoptosis including JNK activation and nuclear fragmentation. Using compartmentalized culture systems that segregate neuronal cell bodies from axons, proNT-3, acting within the distal axon compartment, elicited sympathetic neuron death and overrode the survival promoting actions of NGF. Together these results raise the intriguing possibility that dysregulation of proneurotrophin processing/release by innervated targets can be deleterious to the neurons projecting to these sites. PMID:19940174

  5. A novel single-cell method provides direct evidence of persistent DNA damage in senescent cells and aged mammalian tissues.

    PubMed

    Galbiati, Alessandro; Beauséjour, Christian; d'Adda di Fagagna, Fabrizio

    2017-01-26

    The DNA damage response (DDR) arrests cell cycle progression until DNA lesions, like DNA double-strand breaks (DSBs), are repaired. The presence of DSBs in cells is usually detected by indirect techniques that rely on the accumulation of proteins at DSBs, as part of the DDR. Such detection may be biased, as some factors and their modifications may not reflect physical DNA damage. The dependency on DDR markers of DSB detection tools has left questions unanswered. In particular, it is known that senescent cells display persistent DDR foci, that we and others have proposed to be persistent DSBs, resistant to endogenous DNA repair activities. Others have proposed that these peculiar DDR foci might not be sites of damaged DNA per se but instead stable chromatin modifications, termed DNA-SCARS. Here, we developed a method, named 'DNA damage in situ ligation followed by proximity ligation assay' (DI-PLA) for the detection and imaging of DSBs in cells. DI-PLA is based on the capture of free DNA ends in fixed cells in situ, by ligation to biotinylated double-stranded DNA oligonucleotides, which are next recognized by antibiotin anti-bodies. Detection is enhanced by PLA with a partner DDR marker at the DSB. We validated DI-PLA by demonstrating its ability to detect DSBs induced by various genotoxic insults in cultured cells and tissues. Most importantly, by DI-PLA, we demonstrated that both senescent cells in culture and tissues from aged mammals retain true unrepaired DSBs associated with DDR markers.

  6. Cysteamine protects gastric epithelial cell monolayers against drug induced damage: evidence for direct cellular protection by sulphydryl compounds.

    PubMed Central

    Romano, M; Razandi, M; Raza, A; Szabo, S; Ivey, J

    1992-01-01

    The sulphydryl containing drug cysteamine protects gastric mucosa in vivo against acute injury. It is not known whether this protection includes a direct effect on gastric cells. Using gastric epithelial cell monolayers derived from a well differentiated human cell line, we evaluated whether cysteamine protects against taurocholate or indomethacin induced damage in conditions which completely exclude the influence of vascular, hormonal, and neural factors. The effect of cysteamine on prostaglandin production by monolayer cells in vitro was also assessed. Cysteamine decreased damage brought about by sodium taurocholate and indomethacin by 40% (p less than 0.01) and 50% (p less than 0.01) respectively. The sulphydryl blocker iodoacetamide prevented the protective effect of cysteamine. Pretreatment with indomethacin, which inhibited prostaglandin E2 output by 60%, did not prevent protection by cysteamine; incubation with cysteamine decreased prostaglandin E2 production by cultured cells. We conclude that (i) cysteamine directly protected gastric epithelial cells in vitro (ii) this protection occurred with indomethacin, which interferes with cellular metabolism of prostaglandins, and taurocholate, whose damaging action at neutral pH is unrelated to interference with prostanoid metabolism, (iii) cysteamine protection in vitro is unrelated to endogenous prostaglandins and is probably mediated by endogenous sulphydryl compounds. Images Figure 1A-1B Figure 1C-1E PMID:1740273

  7. Direct evidence for interaction between human erythroid progenitor cells and a hemoglobin switching activity present in fetal sheep serum.

    PubMed Central

    Stamatoyannopoulos, G; Nakamoto, B; Kurachi, S; Papayannopoulou, T

    1983-01-01

    An activity that induces Hb F to Hb A switching in human cells is present in fetal sheep serum. To test directly the role of cell-to-environment interactions in hemoglobin switching and to define the level of erythroid cell differentiation at which this activity operates, colony transfer experiments were done. Clones grown in the presence of switching activity-containing medium (fetal sheep serum) or control medium (fetal calf serum) were transferred, at the 16- to 30-cell stage, to either fetal sheep serum or fetal calf serum plates and Hb F synthesis was determined in the fully mature erythroid bursts. Fetal calf serum-to-fetal calf serum transfers produced colonies with the high Hb F levels characteristic of undisturbed fetal calf serum-grown clones. Fetal sheep serum-to-fetal calf serum transfers resulted in significant decrease in Hb F synthesis, revealing an interaction between hemoglobin switching activity and cells at an early stage of progenitor cell development. The reduction of Hb F synthesis in fetal calf serum-to-fetal sheep serum transfers indicated that hemoglobin switching activity interacts with cells at later stages of progenitor cell development. Maximal decrease in Hb F synthesis was observed in fetal sheep serum-to-fetal sheep serum transfers, indicating that optimal effects on Hb switching are obtained when the environment that induces Hb switching is present throughout the development of progenitor cells. By splitting single early clones into two parts and transferring them to either a fetal sheep serum or a fetal calf serum environment, these interactions were further demonstrated in the progeny of a single erythroid burst-forming unit. Since all clone transfers were done on cell-free plates, the results of fetal calf serum-to-fetal sheep serum and of fetal sheep serum-to-fetal sheep serum transfers indicated that the switching activity does not require helper cells for its action. These studies show directly that (i) Hb F synthesis is

  8. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells.

    PubMed

    Zubiría, María Guillermina; Alzamendi, Ana; Moreno, Griselda; Rey, María Amanda; Spinedi, Eduardo; Giovambattista, Andrés

    2016-04-02

    We have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs.

  9. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells

    PubMed Central

    Zubiría, María Guillermina; Alzamendi, Ana; Moreno, Griselda; Rey, María Amanda; Spinedi, Eduardo; Giovambattista, Andrés

    2016-01-01

    We have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs. PMID:27049396

  10. Direct hydrocarbon fuel cells

    DOEpatents

    Barnett, Scott A.; Lai, Tammy; Liu, Jiang

    2010-05-04

    The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

  11. S14 protein in breast cancer cells: Direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth

    SciTech Connect

    Martel, Peter M.; Bingham, Chad M.; McGraw, Charles J.; Baker, Christina L.; Morganelli, Peter M.; Meng, Marie Louise; Armstrong, Jessica M.; Moncur, Joel T.; Kinlaw, William B. . E-mail: william.kinlaw@hitchcock.org

    2006-02-01

    Most breast cancers exhibit brisk lipogenesis, and require it for growth. S14 is a lipogenesis-related nuclear protein that is overexpressed in most breast cancers. Sterol response element-binding protein-1c (SREBP-1c) is required for induction of lipogenesis-related genes, including S14 and fatty acid synthase (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested that SREBP-1c drives lipogenesis in tumors as well. We directly tested the hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of progestin in T47D breast cancer cells. Dominant-negative SREBP-1c inhibited induction of S14 and FAS mRNAs by progestin, while active SREBP-1c induced without hormone and superinduced in its presence. Changes in S14 mRNA were reflected in protein levels. A lag time and lack of progestin response elements indicated that S14 and FAS gene activation by progestin is indirect. Knockdown of S14 reduced, whereas overexpression stimulated, T47D cell growth, while nonlipogenic MCF10a mammary epithelial cells were not growth-inhibited. These data directly demonstrate that SREBP-1c drives S14 gene expression in breast cancer cells, and progestin magnifies that effect via an indirect mechanism. This supports the prediction, based on S14 gene amplification and overexpression in breast tumors, that S14 augments breast cancer cell growth and survival.

  12. Direct Evidence of Mesenchymal Stem Cell Tropism for Tumor and Wounding Microenvironments using In Vivo Bioluminescence Imaging

    PubMed Central

    Kidd, Shannon; Spaeth, Erika; Dembinski, Jennifer L.; Dietrich, Martin; Watson, Keri; Klopp, Ann; Battula, Lokesh; Weil, Micheal; Andreeff, Michael; Marini, Frank C.

    2014-01-01

    Multipotent mesenchymal stromal/stem cells (MSC) have shown potential clinical utility. However, previous assessments of MSC behavior in recipients have relied on visual detection in host tissue following sacrifice, failing to monitor in vivo MSC dispersion in a single animal and limiting the number of variables that can be observed concurrently. In this study, we utilized noninvasive, in vivo bioluminescent imaging to determine conditions under which MSC selectively engraft in sites of inflammation. MSC modified to express firefly luciferase (MSC-ffLuc) were injected into healthy mice or mice bearing inflammatory insults, and MSC localization was followed with bioluminescent imaging. Inflammatory insults investigated included cutaneous needle-stick and surgical incision wounds, as well as xenogeneic and syngeneic tumors. We also compared tumor models in which MSC were intraveneously or intraperitoneally delivered. Our results demonstrate hMSC-ffLuc systemically delivered to non-tumor bearing animals initially reside in the lungs, then egress to the liver and spleen and decrease in signal over time. However, hMSC in wounded mice engraft and remain detectable only in injured sites. Similarly, in syngeneic and xenogeneic breast carcinoma-bearing mice, bioluminescent detection of systemically delivered MSC revealed persistent, specific co-localization with sites of tumor development. This pattern of tropism was also observed in an ovarian tumor model in which MSC were IP injected. In this study we have identified conditions under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time. Importantly, these consistent findings were independent of tumor type, immunocompetence and route of MSC delivery. PMID:19650040

  13. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging.

    PubMed

    Kidd, Shannon; Spaeth, Erika; Dembinski, Jennifer L; Dietrich, Martin; Watson, Keri; Klopp, Ann; Battula, Venkata Lokesh; Weil, Micheal; Andreeff, Michael; Marini, Frank C

    2009-10-01

    Multipotent mesenchymal stromal/stem cells (MSC) have shown potential clinical utility. However, previous assessments of MSC behavior in recipients have relied on visual detection in host tissue following sacrifice, failing to monitor in vivo MSC dispersion in a single animal and limiting the number of variables that can be observed concurrently. In this study, we used noninvasive, in vivo bioluminescent imaging to determine conditions under which MSC selectively engraft in sites of inflammation. MSC modified to express firefly luciferase (ffLuc-MSC) were injected into healthy mice or mice bearing inflammatory insults, and MSC localization was followed with bioluminescent imaging. The inflammatory insults investigated included cutaneous needle-stick and surgical incision wounds, as well as xenogeneic and syngeneic tumors. We also compared tumor models in which MSC were i.v. or i.p. delivered. Our results demonstrate that ffLuc-expressing human MSC (hMSC) systemically delivered to nontumor-bearing animals initially reside in the lungs, then egress to the liver and spleen, and decrease in signal over time. However, hMSC in wounded mice engraft and remain detectable only at injured sites. Similarly, in syngeneic and xenogeneic breast carcinoma-bearing mice, bioluminescent detection of systemically delivered MSC revealed persistent, specific colocalization with sites of tumor development. This pattern of tropism was also observed in an ovarian tumor model in which MSC were i.p. injected. In this study, we identified conditions under which MSC tropism and selective engraftment in sites of inflammation can be monitored by bioluminescent imaging over time. Importantly, these consistent findings were independent of tumor type, immunocompetence, and route of MSC delivery.

  14. Evidence for direct cellular protective effect of PL-10 substances (synthesized parts of body protection compound, BPC) and their specificity to gastric mucosal cells.

    PubMed

    Bódis, B; Karádi, O; Németh, P; Dohoczky, C; Kolega, M; Mózsik, G

    1997-01-01

    The direct gastric mucosal cellular effect of four PL-10 substances (a synthesized part of human body protection compound, BPC containing 14 or 15 amino acids) was studied on freshly isolated rat gastric mucosal cells and on a mouse myeloma cell line (Sp2/0-Ag14) in an ethanol-induced cell injury model. The examined substances were not toxic for the cells. Two of them proved to be significantly protective against the direct cellular damaging effect of ethanol (PL 10.1.15AK-3 in 5 microg/ml dose and PL 10.1.AK14-2 dose-dependently, ED50=50 ng/ml) on gastric mucosal cells. This cytoprotective effect was failured on mouse myeloma cells. Based on these results a part of the in vivo protection induced by BPC seems to be a direct cellular protective effect to gastric mucosal cells.

  15. Direct visualization of cell movement in the embryonic olfactory bulb using green fluorescent protein transgenic mice: evidence for rapid tangential migration of neural cell precursors.

    PubMed

    Yamamoto, Kazuhiro; Yamaguchi, Masahiro; Okabe, Shigeo

    2005-02-01

    We analyzed motile behavior of neuronal precursor cells in the intact olfactory bulbs (OBs) using transgenic mice expressing GFP under the control of T alpha 1 tubulin promoter. In the olfactory bulbs at the embryonic days 12.5-14.5, a large number of immature neurons expressed GFP in this transgenic line. Embryonic OBs were maintained in an organ culture system and the migratory behavior of GFP-positive cells was analyzed by time-lapse confocal microscopy. We observed rapid tangential movement of GFP-positive cells in the ventral olfactory bulb. In contrast to the typical bipolar morphology of translocating immature neurons within the developing cortex, the motile cells had neither leading nor trailing processes and changed their overall shape frequently. Comparison of the behavior of cells expressing GFP under the control of T alpha 1 tubulin or nestin promoter revealed that rapid motility was specific to cells in the neuronal lineage. The rapid movement was sensitive to an actin perturbing reagent and also dependent on the calcium influx through L-type calcium channels. These results indicate the presence of a specific form of precursor cell migration in the embryonic olfactory bulb.

  16. Direct evidence for a stem cell common to hematopoiesis and its in vitro microenvironment: studies on syngeneic (inbred) Wistar Furth rats

    SciTech Connect

    Islam, A.; Gong, J.K.; Henderson, E.S.

    1988-01-01

    When injected into a group of lethally irradiated syngeneic (inbred) Wistar Furth (WF) rats, suspensions of stromal cells grown in monolayer culture from the marrow of WF rats produced hemopoietic colonies in the spleen and rescued 50% of the rats, while 90% of the non-injected (control) rats died within 30 days and had no hemopoietic colonies in the spleens. Fifty percent of the injected (test) rats which died between days 6 and 22 showed hemopoietic regeneration in the bone marrow, while little or no evidence of hemopoietic regeneration was seen in the control animals. Our results suggest that the marrow stroma grown in vitro contain cells with hemopoietic potential and are transplantable.

  17. Direct evidence for the covalent modification of glutathione-S-transferase P1-1 by electrophilic prostaglandins: implications for enzyme inactivation and cell survival.

    PubMed

    Sánchez-Gómez, Francisco J; Gayarre, Javier; Avellano, M Isabel; Pérez-Sala, Dolores

    2007-01-15

    Glutathione-S-transferases (GST) catalyze the conjugation of electrophilic compounds to glutathione, thus playing a key role in cell survival and tumor chemoresistance. Cyclopentenone prostaglandins (cyPG) are electrophilic eicosanoids that display potent antiproliferative properties, through multiple mechanisms not completely elucidated. Here we show that the cyPG 15-deoxy-Delta(12,14)-PGJ2 (15d-PGJ2) binds to GSTP1-1 covalently, as demonstrated by mass spectrometry and by the use of biotinylated 15d-PGJ2. Moreover, cyPG inactivate GSTP1-1 irreversibly. The presence of the cyclopentenone moiety is important for these effects. Covalent interactions also occur in cells, in which 15d-PGJ2 binds to endogenous GSTP1-1, irreversibly reduces GST free-thiol content and inhibits GST activity. Protein delivery of GSTP1-1 improves cell survival upon serum deprivation whereas 15d-PGJ2-treated GSTP1-1 displays a reduced protective effect. These results show the first evidence for the formation of stable adducts between cyPG and GSTP1-1 and may offer new perspectives for the development of irreversible GST inhibitors as anticancer agents.

  18. Evidence for direct effects of glyphosate on ovarian function: glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro.

    PubMed

    Perego, Maria Chiara; Schutz, Luis F; Caloni, Francesca; Cortinovis, Cristina; Albonico, Marco; Spicer, Leon J

    2016-12-05

    Glyphosate (GLY) is a common herbicide used worldwide but its effect on ovarian function in mammals is unknown. The aim of this study was to determine the potential endocrine disruptor effects of GLY on ovarian function evaluating cell proliferation, steroidogenesis and gene expression using bovine granulosa cells (GC) and theca cells as in vitro models. GC proliferation was impaired (P < 0.05) after exposure to GLY at 0.5, 1.7 and 5 μg ml(-1) . GC progesterone production was not affected (P ≥ 0.05) at all doses tested while estradiol production was inhibited (P < 0.05) by GLY at 5 μg ml(-1) . At the same concentration GLY showed no effect (P ≥ 0.05) on theca cell proliferation and steroidogenesis. At higher concentrations (0.01 and 0.3 mg ml(-1) ), GLY had no significant effect (P ≥ 0.05) on GC proliferation and steroidogenesis. These studies, for the first time, suggest that GLY may affect the reproductive system in cattle via direct action on ovarian function; however, further studies will be required to understand better the mechanism of action and to determine the in vivo reproductive effects of GLY. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Direct demonstration of β1- and evidence against β2- and β3-adrenoceptors, in smooth muscle cells of rat small mesenteric arteries

    PubMed Central

    Briones, Ana M; Daly, Craig J; Jimenez-Altayo, Francesc; Martinez-Revelles, Sonia; Gonzalez, Jose M; McGrath, John C; Vila, Elisabet

    2005-01-01

    Recent evidence supports additional subtypes of vasodilator β-adrenoceptor (β-AR) besides the ‘classical' β2. The aim of this study was to investigate the distribution of β-ARs in the wall of rat mesenteric resistance artery (MRA), to establish the relative roles of β-ARs in smooth muscle and other cell types in mediating vasodilatation and to analyse this in relation to the functional pharmacology. We first examined the vasodilator β-AR subtype using ‘subtype-selective' agonists against the, commonly employed, phenylephrine-induced tone. Concentration-related relaxation was produced by isoprenaline (pEC50: 7.70±0.1) (β1 and β2). Salbutamol (β2), BRL 37344 (β3) and CGP 12177 (atypical β) caused relaxation but were 144, 100 and 263 times less potent than isoprenaline; the ‘β3-adrenoceptor agonist' CL 316243 was ineffective. In arteries precontracted with 5-HT or U 46619, isoprenaline produced concentration-related relaxation but salbutamol, BRL 37344, CGP 12177 and CL 316243 did not. SR 59230A, CGP 12177 and BRL 37344 caused a parallel rightward shift in the concentration–response curve to phenylephrine indicating competitive α1-AR antagonism, explaining the false-positive ‘vasodilator' action against phenylephrine-induced tone. Endothelial denudation but not L-NAME slightly attenuated isoprenaline-mediated vasodilatation in phenylephrine and U 46619 precontracted MRA. The β-AR fluorescent ligand BODIPY TMR-CGP 12177 behaved as an irreversible β1-AR antagonist in MRA and bound to the surface and inside vascular smooth muscle cells in intact vascular wall. β-ARs in smooth muscle cells were observed in a perinuclear location, consistent with the location of Golgi and endoplasmic reticulum. Binding of BODIPY TMR-CGP 12177 was inhibited by BAAM (1 μM) in all three vascular tunics, confirming the presence of β-ARs in adventitia, media and intima. Binding in adventitia was observed in both neuronal and non-neuronal cell types. Lack of co

  20. Protrusion Fluctuations Direct Cell Motion

    PubMed Central

    Caballero, David; Voituriez, Raphaël; Riveline, Daniel

    2014-01-01

    Many physiological phenomena involve directional cell migration. It is usually attributed to chemical gradients in vivo. Recently, other cues have been shown to guide cells in vitro, including stiffness/adhesion gradients or micropatterned adhesive motifs. However, the cellular mechanism leading to these biased migrations remains unknown, and, often, even the direction of motion is unpredictable. In this study, we show the key role of fluctuating protrusions on ratchet-like structures in driving NIH3T3 cell migration. We identified the concept of efficient protrusion and an associated direction index. Our analysis of the protrusion statistics facilitated the quantitative prediction of cell trajectories in all investigated conditions. We varied the external cues by changing the adhesive patterns. We also modified the internal cues using drug treatments, which modified the protrusion activity. Stochasticity affects the short- and long-term steps. We developed a theoretical model showing that an asymmetry in the protrusion fluctuations is sufficient for predicting all measures associated with the long-term motion, which can be described as a biased persistent random walk. PMID:24988339

  1. Directional Excitatory Input to Direction-Selective Ganglion Cells in the Rabbit Retina.

    PubMed

    Percival, Kumiko A; Venkataramani, Sowmya; Smith, Robert G; Rowland Taylor, W

    2017-03-14

    Directional responses in retinal ganglion cells are generated in large part by direction-selective release of GABA from starburst amacrine cells onto direction-selective ganglion cells (DSGCs). The excitatory inputs to DSGCs are also widely reported to be direction-selective, however, recent evidence suggests that glutamate release from bipolar cells is not directional, and directional excitation seen in patch-clamp analyses may be an artifact resulting from incomplete voltage control. Here we test this voltage-clamp-artifact hypothesis in recordings from 62 On-Off DSGCs in the rabbit retina. The strength of the directional excitatory signal varies considerably across the sample of cells, but is not correlated with the strength of directional inhibition, as required for a voltage-clamp artifact. These results implicate additional mechanisms in generating directional excitatory inputs to DSGCs. This article is protected by copyright. All rights reserved.

  2. Establishing direction during chemotaxis in eukaryotic cells.

    PubMed Central

    Rappel, Wouter-Jan; Thomas, Peter J; Levine, Herbert; Loomis, William F

    2002-01-01

    Several recent studies have demonstrated that eukaryotic cells, including amoeboid cells of Dictyostelium discoideum and neutrophils, respond to chemoattractants by translocation of PH-domain proteins to the cell membrane, where these proteins participate in the modulation of the cytoskeleton and relay of the signal. When the chemoattractant is released from a pipette, the localization is found predominantly on the proximal side of the cell. The recruitment of PH-domain proteins, particularly for Dictyostelium cells, occurs very rapidly (<2 s). Thus, the mechanism responsible for the first step in the directional sensing process of a cell must be able to establish an asymmetry on the same time scale. Here, we propose a simple mechanism in which a second messenger, generated by local activation of the membrane, diffuses through the interior of the cell, suppresses the activation of the back of the cell, and converts the temporal gradient into an initial cellular asymmetry. Numerical simulations show that such a mechanism is plausible. Available evidence suggests that the internal inhibitor may be cGMP, which accumulates within less than a second following treatment of cells with external cAMP. PMID:12202361

  3. The direct methanol fuel cell

    SciTech Connect

    Halpert, G.; Narayanan, S.R.; Frank, H.

    1995-08-01

    This presentation describes the approach and progress in the ARPA-sponsored effort to develop a Direct Methanol, Liquid-Feed Fuel Cell (DMLFFC) with a solid Polymer Electrolyte Membrane (PEM) for battery replacement in small portable applications. Using Membrane Electrode Assemblies (MEAs) developed by JPL and Giner, significant voltage was demonstrated at relatively high current densities. The DMLFFC utilizes a 3 percent aqueous solution of methanol that is oxidized directly in the anode (fuel) chamber and oxygen (air) in the cathode chamber to produce water and significant power. The only products are water and CO{sub 2}. The ARPA effort is aimed at replacing the battery in the BA 5590 military radio.

  4. Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: evidence for a direct role of testosterone on regulatory T cell expansion.

    PubMed

    Fijak, Monika; Schneider, Eva; Klug, Jörg; Bhushan, Sudhanshu; Hackstein, Holger; Schuler, Gerhard; Wygrecka, Malgorzata; Gromoll, Jörg; Meinhardt, Andreas

    2011-05-01

    Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4(+) T cells with a strong concomitant increase in the number of regulatory T cells (CD4(+)CD25(+)Foxp3(+)) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1-stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.

  5. Direct methanol fuel cell for portable applications

    SciTech Connect

    Valdez, T.I.; Narayanan, S.R.; Frank, H.; Chun, W.

    1997-12-01

    A five cell direct methanol fuel cell stack has been developed at the Jet Propulsion Laboratory. Presently direct methanol fuel cell technology is being incorporated into a system for portable applications. Electrochemical performance and its dependence on flow rate and temperature for a five cell stack are presented. Water transport data, and water transport mechanisms for direct methanol fuel cells are discussed. Stack response to pulse loads has been characterized. Implications of stack performance and operating conditions on system design have been addressed.

  6. Direct evidence for functional TRPV1/TRPA1 heteromers.

    PubMed

    Fischer, Michael J M; Balasuriya, Dilshan; Jeggle, Pia; Goetze, Tom A; McNaughton, Peter A; Reeh, Peter W; Edwardson, J Michael

    2014-12-01

    Transient receptor potential cation channel, subfamily V, member 1 (TRPV1) plays a key role in sensing environmental hazards and in enhanced pain sensation following inflammation. A considerable proportion of TRPV1-expressing cells also express transient receptor potential cation channel, subfamily A, member 1 (TRPA1). There is evidence for a TRPV1-TRPA1 interaction that is predominantly calcium-dependent, and it has been suggested that the two proteins might form a heteromeric channel. Here, we constructed subunit concatemers to search for direct evidence for such an interaction. We found that a TRPV1::TRPV1 concatemer and TRPV1 formed channels with similar properties. A TRPV1::TRPA1 concatemer was responsive to TRPV1 agonists capsaicin, acidic pH and ethanol, but not to TRPA1 agonists. Isolated TRPV1 and TRPV1::TRPA1 imaged by atomic force microscopy (AFM) both had molecular volumes consistent with the formation of tetrameric channels. Antibodies decorated epitope tags on TRPV1 with a four-fold symmetry, as expected for a homotetramer. In contrast, pairs of antibodies decorated tags on TRPV1::TRPA1 predominantly at 180°, indicating the formation of a channel consisting of two TRPV1::TRPA1 concatemers arranged face to face. TRPV1::TRPA1 was sensitized by PKC activation and could be inhibited by a TRPV1 antagonist. TRPV1::TRPA1 was activated by heat and displayed a threshold and temperature coefficient similar to TRPV1. However, the channel formed by TRPV1::TRPA1 has only two binding sites for capsaicin and shows less total current and a smaller capsaicin-induced shift in voltage-dependent gating than TRPV1::TRPV1 or TRPV1. We conclude that the presence of TRPA1 exerts a functional inhibition on TRPV1.

  7. Directional Summation in Non-direction Selective Retinal Ganglion Cells

    PubMed Central

    Abbas, Syed Y.; Hamade, Khaldoun C.; Yang, Ellen J.; Nawy, Scott; Smith, Robert G.; Pettit, Diana L.

    2013-01-01

    Retinal ganglion cells receive inputs from multiple bipolar cells which must be integrated before a decision to fire is made. Theoretical studies have provided clues about how this integration is accomplished but have not directly determined the rules regulating summation of closely timed inputs along single or multiple dendrites. Here we have examined dendritic summation of multiple inputs along On ganglion cell dendrites in whole mount rat retina. We activated inputs at targeted locations by uncaging glutamate sequentially to generate apparent motion along On ganglion cell dendrites in whole mount retina. Summation was directional and dependent13 on input sequence. Input moving away from the soma (centrifugal) resulted in supralinear summation, while activation sequences moving toward the soma (centripetal) were linear. Enhanced summation for centrifugal activation was robust as it was also observed in cultured retinal ganglion cells. This directional summation was dependent on hyperpolarization activated cyclic nucleotide-gated (HCN) channels as blockade with ZD7288 eliminated directionality. A computational model confirms that activation of HCN channels can override a preference for centripetal summation expected from cell anatomy. This type of direction selectivity could play a role in coding movement similar to the axial selectivity seen in locust ganglion cells which detect looming stimuli. More generally, these results suggest that non-directional retinal ganglion cells can discriminate between input sequences independent of the retina network. PMID:23516351

  8. Air Breathing Direct Methanol Fuel Cell

    DOEpatents

    Ren; Xiaoming

    2003-07-22

    A method for activating a membrane electrode assembly for a direct methanol fuel cell is disclosed. The method comprises operating the fuel cell with humidified hydrogen as the fuel followed by running the fuel cell with methanol as the fuel.

  9. Children Mix Direct and Indirect Speech: Evidence from Pronoun Comprehension

    ERIC Educational Resources Information Center

    Köder, Franziska; Maier, Emar

    2016-01-01

    This study investigates children's acquisition of the distinction between direct speech (Elephant said, "I get the football") and indirect speech ("Elephant said that he gets the football"), by measuring children's interpretation of first, second, and third person pronouns. Based on evidence from various linguistic sources, we…

  10. DIRECT AMMONIA-AIR FUEL CELL.

    DTIC Science & Technology

    Experimental runs were conducted on direct ammonia fuel cells . Effects of temperature, composition, as well as run effect and block effect were...cells and to electrode flooding are discussed. Data on performance of complete laboratory direct ammonia-oxygen fuel cells are presented and discussed. (Author)

  11. Lipopolysaccharide-induced hemolysis: Evidence for direct membrane interactions

    PubMed Central

    Brauckmann, Stephan; Effenberger-Neidnicht, Katharina; de Groot, Herbert; Nagel, Michael; Mayer, Christian; Peters, Jürgen; Hartmann, Matthias

    2016-01-01

    While hemolysis in patients with sepsis is associated with increased mortality its mechanisms are unknown and Toll-like receptor (TLR)-4 mediated effects, complement-mediated hemolysis, or direct cell membrane effects are all conceivable mechanisms. In this study, we tested the hypotheses that toxic lipopolysaccharide (LPS) as well as non-toxic RS-LPS evokes hemolysis (1) by direct membrane effects, and (2) independent of the complement system and TLR-4 activation. We found, that incubation with LPS resulted in a marked time and concentration dependent increase of free hemoglobin concentration and LDH activity in whole blood and washed red cells. Red cell integrity was diminished as shown by decreased osmotic resistance, formation of schistocytes and rolls, and a decrease in red cell membrane stiffness. Non-toxic RS-LPS inhibited the LPS-evoked increase in TNF-α concentration demonstrating its TLR-4 antagonism, but augmented LPS-induced increase in supernatant hemoglobin concentration and membrane disturbances. Removal of plasma components in washed red cell assays failed to attenuate hemolysis. In summary, this study demonstrates direct physicochemical interactions of LPS with red cell membranes resulting in hemolysis under in vitro conditions. It might thus be hypothesized, that not all effects of LPS are mediated by TLR and may explain LPS toxicity in cells missing TLR. PMID:27759044

  12. Direct evidence of hybodont shark predation on Late Jurassic ammonites

    NASA Astrophysics Data System (ADS)

    Vullo, Romain

    2011-06-01

    Sharks are known to have been ammonoid predators, as indicated by analysis of bite marks or coprolite contents. However, body fossil associations attesting to this predator-prey relationship have never been described so far. Here, I report a unique finding from the Late Jurassic of western France: a complete specimen of the Kimmeridgian ammonite Orthaspidoceras bearing one tooth of the hybodont shark Planohybodus. Some possible tooth puncture marks are also observed. This is the first direct evidence of such a trophic link between these two major Mesozoic groups, allowing an accurate identification of both organisms. Although Planohybodus displays a tearing-type dentition generally assumed to have been especially adapted for large unshelled prey, our discovery clearly shows that this shark was also able to attack robust ammonites such as aspidoceratids. The direct evidence presented here provides new insights into the Mesozoic marine ecosystem food webs.

  13. Direct Geoelectrical Evidence of Mass Transfer at the Lab scale

    NASA Astrophysics Data System (ADS)

    Swanson, R. D.; Singha, K.; Day-Lewis, F. D.; Keating, K.; Binley, A.; Clifford, J.; Haggerty, R.

    2011-12-01

    At many field sites, anomalous tailing behavior-- a long, slow decrease of solute concentration in time-- is observed yet cannot be explained with the advection-dispersion model. One explanation for this commonly observed behavior is the exchange of solute between mobile and immobile domains; however, direct experimental observations of this controlling process remain elusive. Circumstantial evidence for a less-mobile phase is typically inferred from tailing behavior observed in fluid samples of the mobile phase. Electrical methods provide a measure of the total solutes in both the immobile and mobile domain and therefore have been hypothesized to provide, in combination with fluid sampling, direct experimental evidence for a less-mobile and mobile model, yet experimental evidence is needed to support this claim. Here, we conduct column solute tracer tests and measure both electrical resistivity and fluid conductivity on unconsolidated, well-sorted sand in addition to fine and coarse fractions of the porous zeolite clinoptilolite. We examine nearly co-located time-lapse standard fluid conductivity and bulk apparent resistivity measurements to identify solute exchange between multiple domains at the lab scale. Our results show extensive tailing behavior in both fluid and bulk electrical conductivity measurements in the zeolite but not in sand, providing evidence for a mobile-immobile framework. Transport parameters are estimated by minimizing the root-mean-square error between the observed and simulated fluid conductivity in COMSOL Multiphysics. These best-fit parameters support our claims of mass transfer occurring in the zeolite columns and provide the first direct electrical evidence of dual-domain mass transport at the lab scale.

  14. Stem cell directed gene therapy.

    PubMed

    Engel, B C; Kohn, D B

    1999-05-01

    A potential therapeutic approach to HIV-1 infection is the genetic modification of cells of a patient to make them resistant to HIV-1. Hematopoietic stem cells are an attractive target for gene therapy of AIDS because of their ability to generate a broad repertoire of mature T lymphocytes, as well as the monocytic cells (macrophages, dendritic cells and microglia) which are also involved in HIV-1 pathogenesis. A number of synthetic "anti-HIV-1 genes" have been developed which inhibit HIV-1 replication. However, current methods for gene transfer into human hematopoietic stem cells, using retroviral vectors derived from the Moloney murine leukemia virus, have been minimally effective. Clinical trials performed to date in which hematopoietic cells from HIV-1-positive patients have been transduced with retroviral vectors and then reinfused have produced low to undetectable levels of gene-containing peripheral blood leukocytes. New vector delivery systems, such as lentiviral vectors, need to be developed to ensure efficient gene transfer and persistent transgene expression to provide life-long resistance to the cells targeted by HIV-1.

  15. Directing the public to evidence-based online content.

    PubMed

    Cooper, Crystale Purvis; Gelb, Cynthia A; Vaughn, Alexandra N; Smuland, Jenny; Hughes, Alexandra G; Hawkins, Nikki A

    2015-04-01

    To direct online users searching for gynecologic cancer information to accurate content, the Centers for Disease Control and Prevention's (CDC) 'Inside Knowledge: Get the Facts About Gynecologic Cancer' campaign sponsored search engine advertisements in English and Spanish. From June 2012 to August 2013, advertisements appeared when US Google users entered search terms related to gynecologic cancer. Users who clicked on the advertisements were directed to relevant content on the CDC website. Compared with the 3 months before the initiative (March-May 2012), visits to the CDC web pages linked to the advertisements were 26 times higher after the initiative began (June-August 2012) (p<0.01), and 65 times higher when the search engine advertisements were supplemented with promotion on television and additional websites (September 2012-August 2013) (p<0.01). Search engine advertisements can direct users to evidence-based content at a highly teachable moment--when they are seeking relevant information.

  16. Random versus directionally persistent cell migration

    PubMed Central

    Petrie, Ryan J.; Doyle, Andrew D.; Yamada, Kenneth M.

    2009-01-01

    Directional migration is an important component of cell motility. Although the basic mechanisms of random cell movement are well characterized, no single model explains the complex regulation of directional migration. Multiple factors operate at each step of cell migration to stabilize lamellipodia and maintain directional migration. Factors such as topography of the extracellular matrix, the cellular polarity machinery, receptor signalling, integrin trafficking and co-receptors, and actin–myosin contraction converge on regulation of the Rho family of GTPases and control of lamellipodial protrusions to promote directional migration. PMID:19603038

  17. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.

    PubMed

    Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H; Hampstead, Benjamin M; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A; Reis, Janine; Richardson, Jessica D; Rotenberg, Alexander; Turkeltaub, Peter E; Woods, Adam J

    2016-01-01

    This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.

  18. Air breathing direct methanol fuel cell

    DOEpatents

    Ren, Xiaoming

    2002-01-01

    An air breathing direct methanol fuel cell is provided with a membrane electrode assembly, a conductive anode assembly that is permeable to air and directly open to atmospheric air, and a conductive cathode assembly that is permeable to methanol and directly contacting a liquid methanol source.

  19. Air breathing direct methanol fuel cell

    DOEpatents

    Ren, Xiaoming; Gottesfeld, Shimshon

    2002-01-01

    An air breathing direct methanol fuel cell is provided with a membrane electrode assembly, a conductive anode assembly that is permeable to air and directly open to atmospheric air, and a conductive cathode assembly that is permeable to methanol and directly contacting a liquid methanol source. Water loss from the cell is minimized by making the conductive cathode assembly hydrophobic and the conductive anode assembly hydrophilic.

  20. Direct evidence of milk consumption from ancient human dental calculus

    PubMed Central

    Warinner, C.; Hendy, J.; Speller, C.; Cappellini, E.; Fischer, R.; Trachsel, C.; Arneborg, J.; Lynnerup, N.; Craig, O. E.; Swallow, D. M.; Fotakis, A.; Christensen, R. J.; Olsen, J. V.; Liebert, A.; Montalva, N.; Fiddyment, S.; Charlton, S.; Mackie, M.; Canci, A.; Bouwman, A.; Rühli, F.; Gilbert, M. T. P.; Collins, M. J.

    2014-01-01

    Milk is a major food of global economic importance, and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread, and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein β-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption, and we identify individuals consuming cattle, sheep, and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies, and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15th century CE. PMID:25429530

  1. Direct evidence of milk consumption from ancient human dental calculus.

    PubMed

    Warinner, C; Hendy, J; Speller, C; Cappellini, E; Fischer, R; Trachsel, C; Arneborg, J; Lynnerup, N; Craig, O E; Swallow, D M; Fotakis, A; Christensen, R J; Olsen, J V; Liebert, A; Montalva, N; Fiddyment, S; Charlton, S; Mackie, M; Canci, A; Bouwman, A; Rühli, F; Gilbert, M T P; Collins, M J

    2014-11-27

    Milk is a major food of global economic importance, and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread, and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein β-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption, and we identify individuals consuming cattle, sheep, and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies, and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15(th) century CE.

  2. Shallow cells in directional solidification

    NASA Technical Reports Server (NTRS)

    Merchant, G. J.; Davis, S. H.

    1989-01-01

    The existing theory on two-dimensional transitions (appropriate to thin parallel-plate geometries) is presented in such a way that it is possible to identify easily conditions for the onset of shallow cells. Conditions are given under which succinonitrile-acetone mixtures should undergo supercritical bifurcation in experimentally accessible ranges. These results suggest a means for the quantitative test of the Mullins and Sekerka (1964) model and its weakly nonlinear extensions.

  3. Direct chemical evidence for eumelanin pigment from the Jurassic period

    PubMed Central

    Glass, Keely; Ito, Shosuke; Wilby, Philip R.; Sota, Takayuki; Nakamura, Atsushi; Bowers, C. Russell; Vinther, Jakob; Dutta, Suryendu; Summons, Roger; Briggs, Derek E. G.; Wakamatsu, Kazumasa; Simon, John D.

    2012-01-01

    Melanin is a ubiquitous biological pigment found in bacteria, fungi, plants, and animals. It has a diverse range of ecological and biochemical functions, including display, evasion, photoprotection, detoxification, and metal scavenging. To date, evidence of melanin in fossil organisms has relied entirely on indirect morphological and chemical analyses. Here, we apply direct chemical techniques to categorically demonstrate the preservation of eumelanin in two > 160 Ma Jurassic cephalopod ink sacs and to confirm its chemical similarity to the ink of the modern cephalopod, Sepia officinalis. Identification and characterization of degradation-resistant melanin may provide insights into its diverse roles in ancient organisms. PMID:22615359

  4. Direct chemical evidence for eumelanin pigment from the Jurassic period.

    PubMed

    Glass, Keely; Ito, Shosuke; Wilby, Philip R; Sota, Takayuki; Nakamura, Atsushi; Bowers, C Russell; Vinther, Jakob; Dutta, Suryendu; Summons, Roger; Briggs, Derek E G; Wakamatsu, Kazumasa; Simon, John D

    2012-06-26

    Melanin is a ubiquitous biological pigment found in bacteria, fungi, plants, and animals. It has a diverse range of ecological and biochemical functions, including display, evasion, photoprotection, detoxification, and metal scavenging. To date, evidence of melanin in fossil organisms has relied entirely on indirect morphological and chemical analyses. Here, we apply direct chemical techniques to categorically demonstrate the preservation of eumelanin in two > 160 Ma Jurassic cephalopod ink sacs and to confirm its chemical similarity to the ink of the modern cephalopod, Sepia officinalis. Identification and characterization of degradation-resistant melanin may provide insights into its diverse roles in ancient organisms.

  5. Nestin(+) cells direct inflammatory cell migration in atherosclerosis.

    PubMed

    Del Toro, Raquel; Chèvre, Raphael; Rodríguez, Cristina; Ordóñez, Antonio; Martínez-González, José; Andrés, Vicente; Méndez-Ferrer, Simón

    2016-09-02

    Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) cells-but not in endothelial cells only- increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis.

  6. Nestin+ cells direct inflammatory cell migration in atherosclerosis

    PubMed Central

    del Toro, Raquel; Chèvre, Raphael; Rodríguez, Cristina; Ordóñez, Antonio; Martínez-González, José; Andrés, Vicente; Méndez-Ferrer, Simón

    2016-01-01

    Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin+ cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin+ cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin+ cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin+ cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin+ stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin+ cells—but not in endothelial cells only— increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis. PMID:27586429

  7. Methods of conditioning direct methanol fuel cells

    DOEpatents

    Rice, Cynthia; Ren, Xiaoming; Gottesfeld, Shimshon

    2005-11-08

    Methods for conditioning the membrane electrode assembly of a direct methanol fuel cell ("DMFC") are disclosed. In a first method, an electrical current of polarity opposite to that used in a functioning direct methanol fuel cell is passed through the anode surface of the membrane electrode assembly. In a second method, methanol is supplied to an anode surface of the membrane electrode assembly, allowed to cross over the polymer electrolyte membrane of the membrane electrode assembly to a cathode surface of the membrane electrode assembly, and an electrical current of polarity opposite to that in a functioning direct methanol fuel cell is drawn through the membrane electrode assembly, wherein methanol is oxidized at the cathode surface of the membrane electrode assembly while the catalyst on the anode surface is reduced. Surface oxides on the direct methanol fuel cell anode catalyst of the membrane electrode assembly are thereby reduced.

  8. Generation of diverse neural cell types through direct conversion

    PubMed Central

    Petersen, Gayle F; Strappe, Padraig M

    2016-01-01

    A characteristic of neurological disorders is the loss of critical populations of cells that the body is unable to replace, thus there has been much interest in identifying methods of generating clinically relevant numbers of cells to replace those that have been damaged or lost. The process of neural direct conversion, in which cells of one lineage are converted into cells of a neural lineage without first inducing pluripotency, shows great potential, with evidence of the generation of a range of functional neural cell types both in vitro and in vivo, through viral and non-viral delivery of exogenous factors, as well as chemical induction methods. Induced neural cells have been proposed as an attractive alternative to neural cells derived from embryonic or induced pluripotent stem cells, with prospective roles in the investigation of neurological disorders, including neurodegenerative disease modelling, drug screening, and cellular replacement for regenerative medicine applications, however further investigations into improving the efficacy and safety of these methods need to be performed before neural direct conversion becomes a clinically viable option. In this review, we describe the generation of diverse neural cell types via direct conversion of somatic cells, with comparison against stem cell-based approaches, as well as discussion of their potential research and clinical applications. PMID:26981169

  9. Discrimination and the HPA axis: current evidence and future directions.

    PubMed

    Busse, David; Yim, Ilona S; Campos, Belinda; Marshburn, Christopher K

    2017-02-02

    Numerous studies suggest that discrimination is associated with poor physical and mental health outcomes. Whereas the cardiovascular system has been extensively studied as a potential pathway linking discrimination with disease, the role of the hypothalamic-pituitary-adrenal (HPA) axis remains understudied. We conducted a systematic review of research on discrimination and related constructs as predictors and correlates of HPA axis activity. Twenty seven studies (10 experimental, 17 observational) met inclusion criteria. Studies suggest that discrimination is associated with alterations in HPA axis activity and that the direction of this association depends on the timing and chronicity of the discrimination experience. There is also evidence of important modulating variables (race, socioeconomic status) and contextual confounders (emotional, situational) that warrant further study. Accounting for the HPA axis in addition to the cardiovascular system will contribute to a more comprehensive understanding of the biobehavioral pathways contributing to physical and mental health inequities related to discrimination.

  10. Record dynamics: Direct experimental evidence from jammed colloids

    NASA Astrophysics Data System (ADS)

    Robe, Dominic M.; Boettcher, Stefan; Sibani, Paolo; Yunker, Peter

    2016-11-01

    In a broad class of complex materials a quench leads to a multi-scaled relaxation process known as aging. To explain its commonality and the astounding insensitivity to most microscopic details, record dynamics (RD) posits that a small set of increasingly rare and irreversible events, so-called quakes, controls the dynamics. While key predictions of RD are known to concur with a number of experimental and simulational results, its basic assumption on the nature of quake statistics has proven extremely difficult to verify experimentally. The careful distinction of rare (“record”) cage-breaking events from in-cage rattle accomplished in previous experiments on jammed colloids, enables us to extract the first direct experimental evidence for the fundamental hypothesis of RD that the rate of quakes decelerates with the inverse of the system age. The resulting description shows the predicted growth of the particle mean square displacement and of a mesoscopic lengthscale with the logarithm of time.

  11. Photochemistry. Evidence for direct molecular oxygen production in CO₂ photodissociation.

    PubMed

    Lu, Zhou; Chang, Yih Chung; Yin, Qing-Zhu; Ng, C Y; Jackson, William M

    2014-10-03

    Photodissociation of carbon dioxide (CO2) has long been assumed to proceed exclusively to carbon monoxide (CO) and oxygen atom (O) primary products. However, recent theoretical calculations suggested that an exit channel to produce C + O2 should also be energetically accessible. Here we report the direct experimental evidence for the C + O2 channel in CO2 photodissociation near the energetic threshold of the C((3)P) + O2(X(3)Σ(g)(-)) channel with a yield of 5 ± 2% using vacuum ultraviolet laser pump-probe spectroscopy and velocity-map imaging detection of the C((3)PJ) product between 101.5 and 107.2 nanometers. Our results may have implications for nonbiological oxygen production in CO2-heavy atmospheres.

  12. Direct geoelectrical evidence of mass transfer at the laboratory scale

    USGS Publications Warehouse

    Swanson, Ryan D.; Singha, Kamini; Day-Lewis, Frederick D.; Binley, Andrew; Keating, Kristina; Haggerty, Roy

    2012-01-01

    Previous field-scale experimental data and numerical modeling suggest that the dual-domain mass transfer (DDMT) of electrolytic tracers has an observable geoelectrical signature. Here we present controlled laboratory experiments confirming the electrical signature of DDMT and demonstrate the use of time-lapse electrical measurements in conjunction with concentration measurements to estimate the parameters controlling DDMT, i.e., the mobile and immobile porosity and rate at which solute exchanges between mobile and immobile domains. We conducted column tracer tests on unconsolidated quartz sand and a material with a high secondary porosity: the zeolite clinoptilolite. During NaCl tracer tests we collected nearly colocated bulk direct-current electrical conductivity (σb) and fluid conductivity (σf) measurements. Our results for the zeolite show (1) extensive tailing and (2) a hysteretic relation between σf and σb, thus providing evidence of mass transfer not observed within the quartz sand. To identify best-fit parameters and evaluate parameter sensitivity, we performed over 2700 simulations of σf, varying the immobile and mobile domain and mass transfer rate. We emphasized the fit to late-time tailing by minimizing the Box-Cox power transformed root-mean square error between the observed and simulated σf. Low-field proton nuclear magnetic resonance (NMR) measurements provide an independent quantification of the volumes of the mobile and immobile domains. The best-fit parameters based on σf match the NMR measurements of the immobile and mobile domain porosities and provide the first direct electrical evidence for DDMT. Our results underscore the potential of using electrical measurements for DDMT parameter inference.

  13. Direct geoelectrical evidence of mass transfer at the laboratory scale

    NASA Astrophysics Data System (ADS)

    Swanson, Ryan D.; Singha, Kamini; Day-Lewis, Frederick D.; Binley, Andrew; Keating, Kristina; Haggerty, Roy

    2012-10-01

    Previous field-scale experimental data and numerical modeling suggest that the dual-domain mass transfer (DDMT) of electrolytic tracers has an observable geoelectrical signature. Here we present controlled laboratory experiments confirming the electrical signature of DDMT and demonstrate the use of time-lapse electrical measurements in conjunction with concentration measurements to estimate the parameters controlling DDMT, i.e., the mobile and immobile porosity and rate at which solute exchanges between mobile and immobile domains. We conducted column tracer tests on unconsolidated quartz sand and a material with a high secondary porosity: the zeolite clinoptilolite. During NaCl tracer tests we collected nearly colocated bulk direct-current electrical conductivity (σb) and fluid conductivity (σf) measurements. Our results for the zeolite show (1) extensive tailing and (2) a hysteretic relation between σf and σb, thus providing evidence of mass transfer not observed within the quartz sand. To identify best-fit parameters and evaluate parameter sensitivity, we performed over 2700 simulations of σf, varying the immobile and mobile domain and mass transfer rate. We emphasized the fit to late-time tailing by minimizing the Box-Cox power transformed root-mean square error between the observed and simulated σf. Low-field proton nuclear magnetic resonance (NMR) measurements provide an independent quantification of the volumes of the mobile and immobile domains. The best-fit parameters based on σf match the NMR measurements of the immobile and mobile domain porosities and provide the first direct electrical evidence for DDMT. Our results underscore the potential of using electrical measurements for DDMT parameter inference.

  14. Anger inhibition and pain: conceptualizations, evidence and new directions.

    PubMed

    Burns, John W; Quartana, Phillip J; Bruehl, Stephen

    2008-06-01

    Anger and how anger is regulated appear to affect acute and chronic pain intensity. The inhibition of anger (anger-in), in particular, has received much attention, and it is widely believed that suppressing or inhibiting the verbal or physical expression of anger is related to increased pain severity. We examine theoretical accounts for expecting that anger inhibition should affect pain, and review evidence for this claim. We suggest that the evidence for a link between trait anger-in (the self-reported tendency to inhibit anger expression when angry) and acute and chronic pain severity is quite limited owing to a number of factors including a inadequate definition of trait anger-in embodied in the popular anger-in subscale of Spielberger's Anger Expression Inventory, and a strong overlap between trait anger-in scores and measures of general negative affect (NA). We argue that in order to determine whether something unique to the process of anger inhibition exerts direct effects on subsequent pain intensity, new conceptualizations and approaches are needed that go beyond self-report assessments of trait anger-in. We present one model of anger inhibition and pain that adopts elements of Wegner's ironic process theory of thought suppression. Findings from this emerging research paradigm indicate that state anger suppression (suppression manipulated in the laboratory) may indeed affect sensitivity to subsequent painful stimuli, and we outline potentially productive avenues of future inquiry that build on this model. We conclude that although studies employing correlational designs and self-reports of trait anger-in have not upheld the claim that anger inhibition affects pain severity, evidence from studies using new models suggests that actually inhibiting anger expression during a provocative event may increase perceived pain at a later time.

  15. Lightweight Stacks of Direct Methanol Fuel Cells

    NASA Technical Reports Server (NTRS)

    Narayanan, Sekharipuram; Valdez, Thomas

    2004-01-01

    An improved design concept for direct methanol fuel cells makes it possible to construct fuel-cell stacks that can weigh as little as one-third as much as do conventional bipolar fuel-cell stacks of equal power. The structural-support components of the improved cells and stacks can be made of relatively inexpensive plastics. Moreover, in comparison with conventional bipolar fuel-cell stacks, the improved fuel-cell stacks can be assembled, disassembled, and diagnosed for malfunctions more easily. These improvements are expected to bring portable direct methanol fuel cells and stacks closer to commercialization. In a conventional bipolar fuel-cell stack, the cells are interspersed with bipolar plates (also called biplates), which are structural components that serve to interconnect the cells and distribute the reactants (methanol and air). The cells and biplates are sandwiched between metal end plates. Usually, the stack is held together under pressure by tie rods that clamp the end plates. The bipolar stack configuration offers the advantage of very low internal electrical resistance. However, when the power output of a stack is only a few watts, the very low internal resistance of a bipolar stack is not absolutely necessary for keeping the internal power loss acceptably low.

  16. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  17. A review of induced pluripotent stem cell, direct conversion by trans-differentiation, direct reprogramming and oligodendrocyte differentiation.

    PubMed

    Prasad, Ankshita; Manivannan, Janani; Loong, Daniel T B; Chua, Soo M; Gharibani, Payam M; All, Angelo H

    2016-03-01

    Rapid progress in the field of stem cell therapy and cellular reprogramming provides convincing evidence of its feasibility in treating a wide range of pathologies through autologous cell replacement therapy. This review article describes in detail on three widely used approaches of somatic cell reprogramming: induced pluripotent stem cells, direct conversion and direct reprogramming, in the context of demyelination in the CNS. The potential limitations of each reprogramming technique are reviewed along with their distinct molecular approach to reprogramming. This is followed by an analysis on the scopes and challenges of its translational applications in deriving oligodendrocyte progenitor cells and oligodendrocytes for cell replacement treatment of demyelinating conditions in the CNS.

  18. Direct chemical evidence for widespread dairying in prehistoric Britain

    PubMed Central

    Copley, M. S.; Berstan, R.; Dudd, S. N.; Docherty, G.; Mukherjee, A. J.; Straker, V.; Payne, S.; Evershed, R. P.

    2003-01-01

    Domesticated animals formed an important element of farming practices in prehistoric Britain, a fact revealed through the quantity and variety of animal bone typically found at archaeological sites. However, it is not known whether the ruminant animals were raised purely for their tissues (e.g., meat) or alternatively were exploited principally for their milk. Absorbed organic residues from pottery from 14 British prehistoric sites were investigated for evidence of the processing of dairy products. Our ability to detect dairy fats rests on the observation that the δ13C values of the C18:0 fatty acids in ruminant dairy fats are ≈2.3‰ lower than in ruminant adipose fats. This difference can be ascribed to (i) the inability of the mammary gland to biosynthesize C18:0; (ii) the biohydrogenation of dietary unsaturated fatty acids in the rumen; and (iii) differences (i.e., 8.1‰) in the δ13C values of the plant dietary fatty acids and carbohydrates. The lipids from a total of 958 archaeological pottery vessels were extracted, and the compound-specific δ13C values of preserved fatty acids (C16:0 and C18:0) were determined via gas chromatography-combustion-isotope ratio mass spectrometry. The results provide direct evidence for the exploitation of domesticated ruminant animals for dairy products at all Neolithic, Bronze Age, and Iron Age settlements in Britain. Most significantly, studies of pottery from a range of key early Neolithic sites confirmed that dairying was a widespread activity in this period and therefore probably well developed when farming was introduced into Britain in the fifth millennium B.C. PMID:12574520

  19. Advances in direct oxidation methanol fuel cells

    NASA Technical Reports Server (NTRS)

    Surampudi, S.; Narayanan, S. R.; Vamos, E.; Frank, H.; Halpert, G.; Laconti, Anthony B.; Kosek, J.; Prakash, G. K. Surya; Olah, G. A.

    1993-01-01

    Fuel cells that can operate directly on fuels such as methanol are attractive for low to medium power applications in view of their low weight and volume relative to other power sources. A liquid feed direct methanol fuel cell has been developed based on a proton exchange membrane electrolyte and Pt/Ru and Pt catalyzed fuel and air/O2 electrodes, respectively. The cell has been shown to deliver significant power outputs at temperatures of 60 to 90 C. The cell voltage is near 0.5 V at 300 mA/cm(exp 2) current density and an operating temperature of 90 C. A deterrent to performance appears to be methanol crossover through the membrane to the oxygen electrode. Further improvements in performance appear possible by minimizing the methanol crossover rate.

  20. Direct formate fuel cells: A review

    NASA Astrophysics Data System (ADS)

    An, L.; Chen, R.

    2016-07-01

    Direct formate fuel cells (DFFC), which convert the chemical energy stored in formate directly into electricity, are recently attracting more attention, primarily because of the use of the carbon-neutral fuel and the low-cost electrocatalytic and membrane materials. As an emerging energy technology, the DFFC has made a rapid progress in recent years (currently, the state-of-the-art power density is 591 mW cm-2 at 60 °C). This article provides a review of past research on the development of this type of fuel cell, including the working principle, mechanisms and materials of the electrocatalytic oxidation of formate, singe-cell designs and performance, as well as innovative system designs. In addition, future perspectives with regard to the development of this fuel cell system are also highlighted.

  1. Direct Cytoskeleton Forces Cause Membrane Softening in Red Blood Cells

    PubMed Central

    Rodríguez-García, Ruddi; López-Montero, Iván; Mell, Michael; Egea, Gustavo; Gov, Nir S.; Monroy, Francisco

    2015-01-01

    Erythrocytes are flexible cells specialized in the systemic transport of oxygen in vertebrates. This physiological function is connected to their outstanding ability to deform in passing through narrow capillaries. In recent years, there has been an influx of experimental evidence of enhanced cell-shape fluctuations related to metabolically driven activity of the erythroid membrane skeleton. However, no direct observation of the active cytoskeleton forces has yet been reported to our knowledge. Here, we show experimental evidence of the presence of temporally correlated forces superposed over the thermal fluctuations of the erythrocyte membrane. These forces are ATP-dependent and drive enhanced flickering motions in human erythrocytes. Theoretical analyses provide support for a direct force exerted on the membrane by the cytoskeleton nodes as pulses of well-defined average duration. In addition, such metabolically regulated active forces cause global membrane softening, a mechanical attribute related to the functional erythroid deformability. PMID:26083919

  2. Direct Numerical Simulation of Cell Printing

    NASA Astrophysics Data System (ADS)

    Qiao, Rui; He, Ping

    2010-11-01

    Structural cell printing, i.e., printing three dimensional (3D) structures of cells held in a tissue matrix, is gaining significant attention in the biomedical community. The key idea is to use desktop printer or similar devices to print cells into 3D patterns with a resolution comparable to the size of mammalian cells, similar to that in living organs. Achieving such a resolution in vitro can lead to breakthroughs in areas such as organ transplantation and understanding of cell-cell interactions in truly 3D spaces. Although the feasibility of cell printing has been demonstrated in the recent years, the printing resolution and cell viability remain to be improved. In this work, we investigate one of the unit operations in cell printing, namely, the impact of a cell-laden droplet into a pool of highly viscous liquids using direct numerical simulations. The dynamics of droplet impact (e.g., crater formation and droplet spreading and penetration) and the evolution of cell shape and internal stress are quantified in details.

  3. Experimental evidence of directivity-enhancing mechanisms in nonlinear lattices

    NASA Astrophysics Data System (ADS)

    Ganesh, R.; Gonella, Stefano

    2017-02-01

    In this letter, we experimentally investigate the directional characteristics of propagating, finite-amplitude wave packets in lattice materials, with an emphasis on the functionality enhancement due to the nonlinearly generated higher harmonics. To this end, we subject a thin, periodically perforated sheet to out-of-plane harmonic excitations, and we design a systematic measurement and data processing routine that leverages the full-wavefield reconstruction capabilities of a laser vibrometer to precisely delineate the effects of nonlinearity. We demonstrate experimentally that the interplay of dispersion, nonlinearity, and modal complexity which is involved in the generation and propagation of higher harmonics gives rise to secondary wave packets with characteristics that conform to the dispersion relation of the corresponding linear structure. Furthermore, these nonlinearly generated wave features display modal and directional characteristics that are complementary to those exhibited by the fundamental harmonic, thus resulting in an augmentation of the functionality landscape of the lattice. These results provide a proof of concept for the possibility to engineer the nonlinear wave response of mechanical metamaterials through a geometric and topological design of the unit cell.

  4. Direct evidence for kinetic effects associated with solar wind reconnection.

    PubMed

    Xu, Xiaojun; Wang, Yi; Wei, Fengsi; Feng, Xueshang; Deng, Xiaohua; Ma, Yonghui; Zhou, Meng; Pang, Ye; Wong, Hon-Cheng

    2015-01-28

    Kinetic effects resulting from the two-fluid physics play a crucial role in the fast collisionless reconnection, which is a process to explosively release massive energy stored in magnetic fields in space and astrophysical plasmas. In-situ observations in the Earth's magnetosphere provide solid consistence with theoretical models on the point that kinetic effects are required in the collisionless reconnection. However, all the observations associated with solar wind reconnection have been analyzed in the context of magnetohydrodynamics (MHD) although a lot of solar wind reconnection exhausts have been reported. Because of the absence of kinetic effects and substantial heating, whether the reconnections are still ongoing when they are detected in the solar wind remains unknown. Here, by dual-spacecraft observations, we report a solar wind reconnection with clear Hall magnetic fields. Its corresponding Alfvenic electron outflow jet, derived from the decouple between ions and electrons, is identified, showing direct evidence for kinetic effects that dominate the collisionless reconnection. The turbulence associated with the exhaust is a kind of background solar wind turbulence, implying that the reconnection generated turbulence has not much developed.

  5. Direct behavioral evidence for retronasal olfaction in rats.

    PubMed

    Gautam, Shree Hari; Verhagen, Justus V

    2012-01-01

    The neuroscience of flavor perception is becoming increasingly important to understand abnormal feeding behaviors and associated chronic diseases such as obesity. Yet, flavor research has mainly depended on human subjects due to the lack of an animal model. A crucial step towards establishing an animal model of flavor research is to determine whether the animal uses the retronasal mode of olfaction, an essential element of flavor perception. We designed a go- no go behavioral task to test the rat's ability to detect and discriminate retronasal odorants. In this paradigm, tasteless aqueous solutions of odorants were licked by water-restricted head-fixed rats from a lick spout. Orthonasal contamination was avoided by employing a combination of a vacuum around the lick-spout and blowing clean air toward the nose. Flow models support the effectiveness of both approaches. The licked odorants were successfully discriminated by rats. Moreover, the tasteless odorant amyl acetate was reliably discriminated against pure distilled water in a concentration-dependent manner. The results from this retronasal odor discrimination task suggest that rats are capable of smelling retronasally. This direct behavioral evidence establishes the rat as a useful animal model for flavor research.

  6. Excitability changes induced in the human auditory cortex by transcranial direct current stimulation: direct electrophysiological evidence.

    PubMed

    Zaehle, Tino; Beretta, Manuela; Jäncke, Lutz; Herrmann, Christoph S; Sandmann, Pascale

    2011-11-01

    Transcranial direct current stimulation (tDCS) can systematically modify behavior by inducing changes in the underlying brain function. Objective electrophysiological evidence for tDCS-induced excitability changes has been demonstrated for the visual and somatosensory cortex, while evidence for excitability changes in the auditory cortex is lacking. In the present study, we applied tDCS over the left temporal as well as the left temporo-parietal cortex and investigated tDCS-induced effects on auditory evoked potentials after anodal, cathodal, and sham stimulation. Results show that anodal and cathodal tDCS can modify auditory cortex reactivity. Moreover, auditory evoked potentials were differentially modulated as a function of site of stimulation. While anodal tDCS over the temporal cortex increased auditory P50 amplitudes, cathodal tDCS over the temporo-parietal cortex induced larger N1 amplitudes. The results directly demonstrate excitability changes in the auditory cortex induced by active tDCS over the temporal and temporo-parietal cortex and might contribute to the understanding of mechanisms involved in the successful treatment of auditory disorders like tinnitus via tDCS.

  7. Alignment of cell division axes in directed epithelial cell migration

    NASA Astrophysics Data System (ADS)

    Marel, Anna-Kristina; Podewitz, Nils; Zorn, Matthias; Oskar Rädler, Joachim; Elgeti, Jens

    2014-11-01

    Cell division is an essential dynamic event in tissue remodeling during wound healing, cancer and embryogenesis. In collective migration, tensile stresses affect cell shape and polarity, hence, the orientation of the cell division axis is expected to depend on cellular flow patterns. Here, we study the degree of orientation of cell division axes in migrating and resting epithelial cell sheets. We use microstructured channels to create a defined scenario of directed cell invasion and compare this situation to resting but proliferating cell monolayers. In experiments, we find a strong alignment of the axis due to directed flow while resting sheets show very weak global order, but local flow gradients still correlate strongly with the cell division axis. We compare experimental results with a previously published mesoscopic particle based simulation model. Most of the observed effects are reproduced by the simulations.

  8. Architecture for portable direct liquid fuel cells

    NASA Astrophysics Data System (ADS)

    Qian, Weimin; Wilkinson, David P.; Shen, Jun; Wang, Haijiang; Zhang, Jiujun

    Direct fuel cells (DFCs) are receiving increased interest for portable power applications. Cell and stack architecture is a vital technical issue for portable DFCs. The architecture of a DFC not only has to meet particular application requirements such as a compact size and easy handling, but also has to ensure desired performance, reliability and fabrication costs. In this paper, the most recent advances related to portable DFCs and their architecture are reviewed. The current status of system architecture, stack/unit cell architecture, flow-field designs and MEA morphology strategies along with analysis are surveyed. In addition, promising methods of passive fuel delivery are also presented.

  9. Improved Direct Methanol Fuel Cell Stack

    SciTech Connect

    Wilson, Mahlon S.; Ramsey, John C.

    2005-03-08

    A stack of direct methanol fuel cells exhibiting a circular footprint. A cathode and anode manifold, tie-bolt penetrations and tie-bolts are located within the circular footprint. Each fuel cell uses two graphite-based plates. One plate includes a cathode active area that is defined by serpentine channels connecting the inlet and outlet cathode manifold. The other plate includes an anode active area defined by serpentine channels connecting the inlet and outlet of the anode manifold, where the serpentine channels of the anode are orthogonal to the serpentine channels of the cathode. Located between the two plates is the fuel cell active region.

  10. DIRECT FUEL/CELL/TURBINE POWER PLANT

    SciTech Connect

    Hossein Ghezel-Ayagh

    2004-05-01

    This report includes the progress in development of Direct FuelCell/Turbine{reg_sign} (DFC/T{reg_sign}) power plants for generation of clean power at very high efficiencies. The DFC/T power system is based on an indirectly heated gas turbine to supplement fuel cell generated power. The DFC/T power generation concept extends the high efficiency of the fuel cell by utilizing the fuel cell's byproduct heat in a Brayton cycle. Features of the DFC/T system include: electrical efficiencies of up to 75% on natural gas, 60% on coal gas, minimal emissions, simplicity in design, direct reforming internal to the fuel cell, reduced carbon dioxide release to the environment, and potential cost competitiveness with existing combined cycle power plants. FCE successfully completed testing of the pre-alpha DFC/T hybrid power plant. This power plant was constructed by integration of a 250kW fuel cell stack and a microturbine. The tests of the cascaded fuel cell concept for achieving high fuel utilizations were completed. The tests demonstrated that the concept results in higher power plant efficiency. Also, the preliminary design of a 40 MW power plant including the key equipment layout and the site plan was completed.

  11. DIRECT FUEL CELL/TURBINE POWER PLANT

    SciTech Connect

    Hossein Ghezel-Ayagh

    2004-11-01

    This report includes the progress in development of Direct FuelCell/Turbine{reg_sign} (DFC/T{reg_sign}) power plants for generation of clean power at very high efficiencies. The DFC/T power system is based on an indirectly heated gas turbine to supplement fuel cell generated power. The DFC/T power generation concept extends the high efficiency of the fuel cell by utilizing the fuel cell's byproduct heat in a Brayton cycle. Features of the DFC/T system include: electrical efficiencies of up to 75% on natural gas, 60% on coal gas, minimal emissions, simplicity in design, direct reforming internal to the fuel cell, reduced carbon dioxide release to the environment, and potential cost competitiveness with existing combined cycle power plants. The operation of sub-MW hybrid Direct FuelCell/Turbine power plant test facility with a Capstone C60 microturbine was initiated in March 2003. The inclusion of the C60 microturbine extended the range of operation of the hybrid power plant to higher current densities (higher power) than achieved in previous tests using a 30kW microturbine. The design of multi-MW DFC/T hybrid systems, approaching 75% efficiency on natural gas, was initiated. A new concept was developed based on clusters of One-MW fuel cell modules as the building blocks. System analyses were performed, including systems for near-term deployment and power plants with long-term ultra high efficiency objectives. Preliminary assessment of the fuel cell cluster concept, including power plant layout for a 14MW power plant, was performed.

  12. TDCS increases cortical excitability: direct evidence from TMS-EEG.

    PubMed

    Romero Lauro, Leonor J; Rosanova, Mario; Mattavelli, Giulia; Convento, Silvia; Pisoni, Alberto; Opitz, Alexander; Bolognini, Nadia; Vallar, Giuseppe

    2014-09-01

    Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the resting membrane potential in a polarity-dependent fashion: anodal stimulation increases cortical excitability in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS, and to what extent the stimulation of a given cerebral region may affect the activity of anatomically connected regions, remain unclear. In the present study, we used a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) in order to explore local and global cortical excitability modulation during and after active and sham tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 15 min of tDCS over the right PPC, while EEG was recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for three temporal windows: 0-50, 50-100, and 100-150 msec. The global index was computed on all 60 channels. The local indexes were computed in six clusters of electrodes: left and right in frontal, parietal and temporal regions. GMFP increased, compared to baseline, both during and after active tDCS in the 0-100 msec temporal window. LMFP increased after the end of stimulation in parietal and frontal clusters bilaterally, while no difference was found in the temporal clusters. In sum, a diffuse rise of cortical excitability occurred, both during and after active tDCS. This evidence highlights the spreading of the effects of anodal tDCS over remote cortical regions of stimulated and contralateral hemispheres.

  13. Chrysler Pentastar direct hydrogen fuel cell program

    SciTech Connect

    Kimble, M.; Deloney, D.

    1995-08-01

    The Chrysler Pentastar Electronics, Inc. Direct Hydrogen Fueled PEM Fuel Cell Hybrid Vehicle Program (DPHV) was initiated 1 July, 1994 with the following mission, {open_quotes}Design, fabricate, and test a Direct Hydrogen Fueled Proton Exchange Membrane (PEM) Fuel Cell System including onboard hydrogen storage, an efficient lightweight fuel cell, a gas management system, peak power augmentation and a complete system controls that can be economically mass produced and comply with all safety environmental and consumer requirements for vehicle applications for the 21st century.{close_quotes} The Conceptual Design for the entire system based upon the selection of an applicable vehicle and performance requirements that are consistent with the PNGV goals will be discussed. A Hydrogen Storage system that has been selected, packaged, and partially tested in accordance with perceived Hydrogen Safety and Infrastructure requirements will be discussed in addition to our Fuel Cell approach along with design of the {open_quotes}real{close_quotes} module. The Gas Management System and the Load Leveling System have been designed and the software programs have been developed and will be discussed along with a complete fuel cell test station that has the capability to test up to a 60 kW fuel cell system.

  14. Direct fuel cell product design improvement

    SciTech Connect

    Maru, H.C.; Farooque, M.

    1996-12-31

    Significant milestones have been attained towards the technology development field testing and commercialization of direct fuel cell power plant since the 1994 Fuel Cell Seminar. Under a 5-year cooperative agreement with the Department of Energy signed in December 1994, Energy Research Corporation (ERC) has been developing the design for a MW-scale direct fuel cell power plant with input from previous technology efforts and the Santa Clara Demonstration Project. The effort encompasses product definition in consultation with the Fuel Cell Commercialization Group, potential customers, as well as extensive system design and packaging. Manufacturing process improvements, test facility construction, cell component scale up, performance and endurance improvements, stack engineering, and critical balance-of-plant development are also addressed. Major emphasis of this product design improvement project is on increased efficiency, compactness and cost reduction to establish a competitive place in the market. A 2.85 MW power plant with an efficiency of 58% and a footprint of 420 m{sup 2} has been designed. Component and subsystem testing is being conducted at various levels. Planning and preparation for verification of a full size prototype unit are in progress. This paper presents the results obtained since the last fuel cell seminar.

  15. Evidence for grid cells in a human memory network.

    PubMed

    Doeller, Christian F; Barry, Caswell; Burgess, Neil

    2010-02-04

    Grid cells in the entorhinal cortex of freely moving rats provide a strikingly periodic representation of self-location which is indicative of very specific computational mechanisms. However, the existence of grid cells in humans and their distribution throughout the brain are unknown. Here we show that the preferred firing directions of directionally modulated grid cells in rat entorhinal cortex are aligned with the grids, and that the spatial organization of grid-cell firing is more strongly apparent at faster than slower running speeds. Because the grids are also aligned with each other, we predicted a macroscopic signal visible to functional magnetic resonance imaging (fMRI) in humans. We then looked for this signal as participants explored a virtual reality environment, mimicking the rats' foraging task: fMRI activation and adaptation showing a speed-modulated six-fold rotational symmetry in running direction. The signal was found in a network of entorhinal/subicular, posterior and medial parietal, lateral temporal and medial prefrontal areas. The effect was strongest in right entorhinal cortex, and the coherence of the directional signal across entorhinal cortex correlated with spatial memory performance. Our study illustrates the potential power of combining single-unit electrophysiology with fMRI in systems neuroscience. Our results provide evidence for grid-cell-like representations in humans, and implicate a specific type of neural representation in a network of regions which supports spatial cognition and also autobiographical memory.

  16. Persistent neural activity in head direction cells

    NASA Technical Reports Server (NTRS)

    Taube, Jeffrey S.; Bassett, Joshua P.; Oman, C. M. (Principal Investigator)

    2003-01-01

    Many neurons throughout the rat limbic system discharge in relation to the animal's directional heading with respect to its environment. These so-called head direction (HD) cells exhibit characteristics of persistent neural activity. This article summarizes where HD cells are found, their major properties, and some of the important experiments that have been conducted to elucidate how this signal is generated. The number of HD and angular head velocity cells was estimated for several brain areas involved in the generation of the HD signal, including the postsubiculum, anterior dorsal thalamus, lateral mammillary nuclei and dorsal tegmental nucleus. The HD cell signal has many features in common with what is known about how neural integration is accomplished in the oculomotor system. The nature of the HD cell signal makes it an attractive candidate for using neural network models to elucidate the signal's underlying mechanisms. The conditions that any network model must satisfy in order to accurately represent how the nervous system generates this signal are highlighted and areas where key information is missing are discussed.

  17. Direct FuelCell/Turbine Power Plant

    SciTech Connect

    Hossein Ghezel-Ayagh

    2004-11-19

    This report includes the progress in development of Direct Fuel Cell/Turbine. (DFC/T.) power plants for generation of clean power at very high efficiencies. The DFC/T power system is based on an indirectly heated gas turbine to supplement fuel cell generated power. The DFC/T power generation concept extends the high efficiency of the fuel cell by utilizing the fuel cell's byproduct heat in a Brayton cycle. Features of the DFC/T system include: electrical efficiencies of up to 75% on natural gas, 60% on coal gas, minimal emissions, simplicity in design, direct reforming internal to the fuel cell, reduced carbon dioxide release to the environment, and potential cost competitiveness with existing combined cycle power plants. FCE successfully completed testing of the pre-alpha sub-MW DFC/T power plant. This power plant was constructed by integration of a 250kW fuel cell stack and a microturbine. Following these proof-of-concept tests, a stand-alone test of the microturbine verified the turbine power output expectations at an elevated (representative of the packaged unit condition) turbine inlet temperature. Preliminary design of the packaged sub-MW alpha DFC/T unit has been completed and procurement activity has been initiated. The preliminary design of a 40 MW power plant including the key equipment layout and the site plan was completed. A preliminary cost estimate for the 40 MW DFC/T plant has also been prepared. The tests of the cascaded fuel cell concept for achieving high fuel utilizations were completed. The tests demonstrated that the concept results in higher power plant efficiency. Alternate stack flow geometries for increased power output/fuel utilization capabilities are also being evaluated.

  18. Direct volume rendering methods for cell structures.

    PubMed

    Martišek, Dalibor; Martišek, Karel

    2012-01-01

    The study of the complicated architecture of cell space structures is an important problem in biology and medical research. Optical cuts of cells produced by confocal microscopes enable two-dimensional (2D) and three-dimensional (3D) reconstructions of observed cells. This paper discuses new possibilities for direct volume rendering of these data. We often encounter 16 or more bit images in confocal microscopy of cells. Most of the information contained in these images is unsubstantial for the human vision. Therefore, it is necessary to use mathematical algorithms for visualization of such images. Present software tools as OpenGL or DirectX run quickly in graphic station with special graphic cards, run very unsatisfactory on PC without these cards and outputs are usually poor for real data. These tools are black boxes for a common user and make it impossible to correct and improve them. With the method proposed, more parameters of the environment can be set, making it possible to apply 3D filters to set the output image sharpness in relation to the noise. The quality of the output is incomparable to the earlier described methods and is worth increasing the computing time. We would like to offer mathematical methods of 3D scalar data visualization describing new algorithms that run on standard PCs very well.

  19. DIRECT FUEL CELL/TURBINE POWER PLANT

    SciTech Connect

    Hossein Ghezel-Ayagh

    2003-05-23

    In this reporting period, a milestone was achieved by commencement of testing and operation of the sub-scale hybrid direct fuel cell/turbine (DFC/T{reg_sign}) power plant. The operation was initiated subsequent to the completion of the construction of the balance-of-plant (BOP) and implementation of process and control tests of the BOP for the subscale DFC/T hybrid system. The construction efforts consisted of finishing the power plant insulation and completion of the plant instrumentation including the wiring and tubing required for process measurement and control. The preparation work also included the development of procedures for facility shake down, conditioning and load testing of the fuel cell, integration of the microturbine, and fuel cell/gas turbine load tests. At conclusion of the construction, the process and control (PAC) tests of BOP, including the microturbine, were initiated.

  20. A micro direct methanol fuel cell demonstrator

    NASA Astrophysics Data System (ADS)

    Wozniak, Konrad; Johansson, David; Bring, Martin; Sanz-Velasco, Anke; Enoksson, Peter

    2004-09-01

    The demand for compact power sources with high energy density is increasing. A direct methanol fuel cell (DMFC) is a renewable energy source which works at near room temperature, and allows for easier liquid fuel storage, which makes it a potential candidate. We report the design, fabrication and characterization of a self-driven DMFC made by micromachining techniques and macro-assembly. Several designs were created on the basis of state-of-the-art DMFCs. A simplified mathematical model was used mainly to design the flow channels and verify the polarization curves, which reveal the output power of a cell. Silicon was used as a substrate for the fabrication of electrodes, and the membrane electrode assembly was provided by Ion Power, Inc. A 0.25 cm2 cell showed a performance of 0.29 mW cm-2 and an open circuit voltage of 0.7 V. Ten microliters of 6 M methanol solution is sufficient to operate the cell for more than 1 h.

  1. Direct FuelCell/Turbine Power Plant

    SciTech Connect

    Hossein Ghezel-Ayagh

    2008-09-30

    This report summarizes the progress made in development of Direct FuelCell/Turbine (DFC/T{reg_sign}) power plants for generation of clean power at very high efficiencies. The DFC/T system employs an indirectly heated Turbine Generator to supplement fuel cell generated power. The concept extends the high efficiency of the fuel cell by utilizing the fuel cell's byproduct heat in a Brayton cycle. Features of the DFC/T system include: electrical efficiencies of up to 75% on natural gas, minimal emissions, reduced carbon dioxide release to the environment, simplicity in design, direct reforming internal to the fuel cell, and potential cost competitiveness with existing combined cycle power plants. Proof-of-concept tests using a sub-MW-class DFC/T power plant at FuelCell Energy's (FCE) Danbury facility were conducted to validate the feasibility of the concept and to measure its potential for electric power production. A 400 kW-class power plant test facility was designed and retrofitted to conduct the tests. The initial series of tests involved integration of a full-size (250 kW) Direct FuelCell stack with a 30 kW Capstone microturbine. The operational aspects of the hybrid system in relation to the integration of the microturbine with the fuel cell, process flow and thermal balances, and control strategies for power cycling of the system, were investigated. A subsequent series of tests included operation of the sub-MW Direct FuelCell/Turbine power plant with a Capstone C60 microturbine. The C60 microturbine extended the range of operation of the hybrid power plant to higher current densities (higher power) than achieved in initial tests using the 30kW microturbine. The proof-of-concept test results confirmed the stability and controllability of operating a fullsize (250 kW) fuel cell stack in combination with a microturbine. Thermal management of the system was confirmed and power plant operation, using the microturbine as the only source of fresh air supply to the

  2. Evidence of directional filtering of travelling ionospheric disturbances.

    NASA Technical Reports Server (NTRS)

    Yeh, K. C.; Webb, H. D.; Cowling, D. H.

    1972-01-01

    Traveling disturbance data obtained by Munro (1953, 1958) in Australia are used to test the concept that thermospheric winds act as a directional filter for gravitational waves. Diurnal contours for winter are presented graphically, showing the number of hours required for gravity waves to reach a height of 300 km.

  3. Selectivity of Direct Methanol Fuel Cell Membranes.

    PubMed

    Aricò, Antonino S; Sebastian, David; Schuster, Michael; Bauer, Bernd; D'Urso, Claudia; Lufrano, Francesco; Baglio, Vincenzo

    2015-11-24

    Sulfonic acid-functionalized polymer electrolyte membranes alternative to Nafion(®) were developed. These were hydrocarbon systems, such as blend sulfonated polyetheretherketone (s-PEEK), new generation perfluorosulfonic acid (PFSA) systems, and composite zirconium phosphate-PFSA polymers. The membranes varied in terms of composition, equivalent weight, thickness, and filler and were investigated with regard to their methanol permeation characteristics and proton conductivity for application in direct methanol fuel cells. The behavior of the membrane electrode assemblies (MEA) was investigated in fuel cell with the aim to individuate a correlation between membrane characteristics and their performance in a direct methanol fuel cell (DMFC). The power density of the DMFC at 60 °C increased according to a square root-like function of the membrane selectivity. This was defined as the reciprocal of the product between area specific resistance and crossover. The power density achieved at 60 °C for the most promising s-PEEK-based membrane-electrode assembly (MEA) was higher than the benchmark Nafion(®) 115-based MEA (77 mW·cm(-2) vs. 64 mW·cm(-2)). This result was due to a lower methanol crossover (47 mA·cm(-2) equivalent current density for s-PEEK vs. 120 mA·cm(-2) for Nafion(®) 115 at 60 °C as recorded at OCV with 2 M methanol) and a suitable area specific resistance (0.15 Ohm cm² for s-PEEK vs. 0.22 Ohm cm² for Nafion(®) 115).

  4. Selectivity of Direct Methanol Fuel Cell Membranes

    PubMed Central

    Aricò, Antonino S.; Sebastian, David; Schuster, Michael; Bauer, Bernd; D’Urso, Claudia; Lufrano, Francesco; Baglio, Vincenzo

    2015-01-01

    Sulfonic acid-functionalized polymer electrolyte membranes alternative to Nafion® were developed. These were hydrocarbon systems, such as blend sulfonated polyetheretherketone (s-PEEK), new generation perfluorosulfonic acid (PFSA) systems, and composite zirconium phosphate–PFSA polymers. The membranes varied in terms of composition, equivalent weight, thickness, and filler and were investigated with regard to their methanol permeation characteristics and proton conductivity for application in direct methanol fuel cells. The behavior of the membrane electrode assemblies (MEA) was investigated in fuel cell with the aim to individuate a correlation between membrane characteristics and their performance in a direct methanol fuel cell (DMFC). The power density of the DMFC at 60 °C increased according to a square root-like function of the membrane selectivity. This was defined as the reciprocal of the product between area specific resistance and crossover. The power density achieved at 60 °C for the most promising s-PEEK-based membrane-electrode assembly (MEA) was higher than the benchmark Nafion® 115-based MEA (77 mW·cm−2 vs. 64 mW·cm−2). This result was due to a lower methanol crossover (47 mA·cm−2 equivalent current density for s-PEEK vs. 120 mA·cm−2 for Nafion® 115 at 60 °C as recorded at OCV with 2 M methanol) and a suitable area specific resistance (0.15 Ohm cm2 for s-PEEK vs. 0.22 Ohm cm2 for Nafion® 115). PMID:26610582

  5. Directed stem cell differentiation: the role of physical forces.

    PubMed

    Clause, Kelly C; Liu, Li J; Tobita, Kimimasa

    2010-04-01

    A number of factors contribute to the control of stem cell fate. In particular, the evidence for how physical forces control the stem cell differentiation program is now accruing. In this review, the authors discuss the types of physical forces: mechanical forces, cell shape, extracellular matrix geometry/properties, and cell-cell contacts and morphogenic factors, which evidence suggests play a role in influencing stem cell fate.

  6. Directed forgetting in young children: evidence for a production deficiency.

    PubMed

    Aslan, Alp; Staudigl, Tobias; Samenieh, Anuscheh; Bäuml, Karl-Heinz T

    2010-12-01

    When people are cued to forget a previously studied list of items and to learn a new list instead, such cuing typically leads to forgetting of the first list and to memory enhancement of the second. In two experiments, we examined such listwise directed forgetting in children (and adults), using a forget cue that placed either high emphasis or low emphasis on the need to forget. In the low-emphasis condition, (adult-like) List 1 forgetting was present in fourth graders, but not in first graders (and kindergartners); in contrast, in the high-emphasis condition, (adult-like) List 1 forgetting was present from first grade on. Only fourth graders showed (adult-like) List 2 enhancement, regardless of task instruction. The finding that first graders showed List 1 forgetting only in the high-emphasis condition points to a production deficiency in first graders' directed forgetting, suggesting that the children are capable of intentional forgetting but fail to do so spontaneously. The finding that first graders showed List 1 forgetting without List 2 enhancement suggests that the two directed-forgetting effects are mediated by different processes with different developmental trajectories.

  7. Self Directed Support and People with Learning Disabilities: A Review of the Published Research Evidence

    ERIC Educational Resources Information Center

    Harkes, Mary Anne; Brown, Michael; Horsburgh, Dorothy

    2014-01-01

    A systematic literature review was undertaken to determine the evidence base underpinning the strategy of Self Directed Support and whether evidence demonstrates that this policy is accessible to everyone with a learning disability. It also sought to identify whether there were any barriers to Self Directed Support for people with severe or…

  8. Further evidence for direct pro-resorptive actions of FSH.

    PubMed

    Sun, Li; Zhang, Zhiyuan; Zhu, Ling-Ling; Peng, Yuanzhen; Liu, Xuan; Li, Jianhua; Agrawal, Manasi; Robinson, Lisa J; Iqbal, Jameel; Blair, Harry C; Zaidi, Mone

    2010-03-26

    We confirm that FSH stimulates osteoclast formation, function and survival to enhance bone resorption. It does so via the activation of a pertussis toxin-sensitive G(i)-coupled FSH receptor that we and others have identified on murine and human osteoclast precursors and mature osteoclasts. FSH additionally enhances the production of several osteoclastogenic cytokines, importantly TNFalpha, likely within the bone marrow microenvironment, to augment its pro-resorptive action. FSH levels in humans rise before estrogen falls, and this hormonal change coincides with the most rapid rates of bone loss. On the basis of accumulating evidence, we reaffirm that FSH contributes to the rapid peri-menopausal and early post-menopausal bone loss, which might thus be amenable to FSH blockade.

  9. Fecal microbiota transplantation: indications, methods, evidence, and future directions.

    PubMed

    Borody, Thomas J; Paramsothy, Sudarshan; Agrawal, Gaurav

    2013-08-01

    Fecal microbiota transplantation (FMT) has attracted great interest in recent years, largely due to the global Clostridium difficile infection (CDI) epidemic and major advances in metagenomic sequencing of the gastrointestinal (GI) microbiota, with growing understanding of its structure and function. FMT is now recommended as the most effective therapy for relapsing CDI and, with further refinement, may even be used in "first-time" CDI. There is interest also in other conditions related to GI dysbiosis--for example, inflammatory bowel disease, irritable bowel syndrome, obesity, and diabetes mellitus--although quality evidence is at present lacking. A few trials are now underway in FMT for ulcerative colitis. Many unanswered questions remain, including FMT methodology--for example, optimal route of administration, what makes a "good donor," safety issues, and long-term effects of FMT.

  10. Direct evidence of acceleration from a distance modulus redshift graph

    NASA Astrophysics Data System (ADS)

    Gong, Yungui; Wang, Anzhong; Wu, Qiang; Zhang, Yuan-Zhong

    2007-08-01

    The energy conditions give upper bounds on the luminosity distance. We apply these upper bounds to the 192 ESSENCE supernova Ia data to show that the Universe has experienced accelerated expansion. This conclusion is drawn directly from the distance modulus redshift graph. In addition to being a very simple method, this method is also totally independent of any cosmological model. From the degeneracy of the distance modulus at low redshift, we argue that the choice of w0 for probing the property of dark energy is misleading. One explicit example is used to support this argument.

  11. DIRECT FUEL CELL/TURBINE POWER PLANT

    SciTech Connect

    Hossein Ghezel-Ayagh

    2003-05-22

    Project activities were focused on the design and construction the sub-scale hybrid Direct Fuel Cell/turbine (DFC/T{reg_sign}) power plant and modification of a Capstone Simple Cycle Model 330 microturbine. The power plant design work included preparation of system flow sheet and performing computer simulations based on conservation of mass and energy. The results of the simulation analyses were utilized to prepare data sheets and specifications for balance-of-plant equipment. Process flow diagram (PFD) and piping and instrumentation diagrams (P&ID) were also completed. The steady state simulation results were used to develop design information for modifying the control functions, and for sizing the heat exchangers required for recuperating the waste heat from the power plant. Line and valve sizes for the interconnecting pipes between the microturbine and the heat recuperators were also identified.

  12. Mutual enhancement of differentiation of osteoblasts and osteocytes occurs through direct cell-cell contact.

    PubMed

    Fujita, Koji; Xing, Qian; Khosla, Sundeep; Monroe, David G

    2014-11-01

    There is increasing evidence that osteocytes regulate multiple aspects of bone remodeling through bi-directional communication with osteoblasts. This is potentially mediated through cell-cell contact via osteocytic dendritic processes, through the activity of secreted factors, or both. To test whether cell-cell contact affects gene expression patterns in osteoblasts and osteocytes, we used a co-culture system where calvarial osteoblasts and IDG-SW3 osteocytes were allowed to touch through a porous membrane, while still being physically separated to allow for phenotypic characterization. Osteoblast/osteocyte cell-contact resulted in up-regulation of osteoblast differentiation genes in the osteoblasts, when compared to wells where no cell contact was allowed. Examination of osteocyte gene expression when in direct contact with osteoblasts also revealed increased expression of osteocyte-specific genes. These data suggest that physical contact mutually enhances both the osteoblastic and osteocytic character of each respective cell type. Interestingly, Gja1 (a gap junction protein) was increased in the osteoblasts only when in direct contact with the osteocytes, suggesting that Gja1 may mediate some of the effects of direct cell contact. To test this hypothesis, we treated the direct contact system with the gap junction inhibitor 18-alpha-glycyrrhetinic acid and found that Bglap expression was significantly inhibited. This suggests that osteocytes may regulate late osteoblast differentiation at least in part through Gja1. Identification of the specific factors involved in the enhancement of differentiation of both osteoblasts and osteocytes when in direct contact will uncover new biology concerning how these bone cells communicate.

  13. Direct evidence of flagellar synchronization through hydrodynamic interactions

    NASA Astrophysics Data System (ADS)

    Brumley, Douglas; Polin, Marco; Wan, Kirsty; Goldstein, Raymond

    2013-11-01

    Eukaryotic cilia and flagella exhibit striking coordination, from the synchronous beating of two flagella in Chlamydomonas to the metachronal waves and large-scale flows displayed by carpets of cilia. However, the precise mechanisms responsible for flagellar synchronization remain unclear. We perform a series of experiments involving two individual flagella in a quiescent fluid. Cells are isolated from the colonial alga Volvox carteri, held in place at a fixed distance d, and oriented so that their flagellar beating planes coincide. In this fashion, we are able to explicitly assess the role of hydrodynamics in achieving synchronization. For closely separated cells, the flagella are capable of exhibiting a phase-locked state for thousands of beats at a time, despite significant differences in their intrinsic frequencies. For intermediate values of d, synchronous periods are interrupted by brief phase slips, while for d >> 1 the flagellar phase difference drifts almost linearly with time. The coupling strength extracted through analysis of the synchronization statistics exhibits excellent agreement with hydrodynamic predictions. This study unambiguously reveals that flagella coupled only through hydrodynamics are capable of exhibiting robust synchrony.

  14. Direct-access retrieval during sentence comprehension: Evidence from Sluicing

    PubMed Central

    Martin, Andrea E.; McElree, Brian

    2011-01-01

    Language comprehension requires recovering meaning from linguistic form, even when the mapping between the two is indirect. A canonical example is ellipsis, the omission of information that is subsequently understood without being overtly pronounced. Comprehension of ellipsis requires retrieval of an antecedent from memory, without prior prediction, a property which enables the study of retrieval in situ (Martin & McElree, 2008, 2009). Sluicing, or inflectional phrase ellipsis, in the presence of a conjunction, presents a test case where a competing antecedent position is syntactically licensed, in contrast with most cases of nonadjacent dependency, including verb phrase ellipsis. We present speed-accuracy tradeoff and eye-movement data inconsistent with the hypothesis that retrieval is accomplished via a syntactically guided search, a particular variant of search not examined in past research. The observed timecourse profiles are consistent with the hypothesis that antecedents are retrieved via a cue-dependent direct-access mechanism susceptible to general memory variables. PMID:21580797

  15. Direct evidence for the Homo-Pan clade.

    PubMed

    Wimmer, Rainer; Kirsch, Stefan; Rappold, Gudrun A; Schempp, Werner

    2002-01-01

    For a long time, the evolutionary relationship between human and African apes, the 'trichotomy problem', has been debated with strong differences in opinion and interpretation. Statistical analyses of different molecular DNA data sets have been carried out and have primarily supported a Homo-Pan clade. An alternative way to address this question is by the comparison of evolutionarily relevant chromosomal breakpoints. Here, we made use of a P1-derived artificial chromosome (PAC)/bacterial artificial chromosome (BAC) contig spanning approximately 2.8 Mb on the long arm of the human Y chromosome, to comparatively map individual PAC clones to chromosomes from great apes, gibbons, and two species of Old World monkeys by fluorescence in-situ hybridization. During our search for evolutionary breakpoints on the Y chromosome, it transpired that a transposition of an approximately 100-kb DNA fragment from chromosome 1 onto the Y chromosome must have occurred in a common ancestor of human, chimpanzee and bonobo. Only the Y chromosomes of these three species contain the chromosome-1-derived fragment; it could not be detected on the Y chromosomes of gorillas or the other primates examined. Thus, this shared derived (synapomorphic) trait provides clear evidence for a Homo-Pan clade independent of DNA sequence analysis.

  16. Hepatic Safety of Atypical Antipsychotics: Current Evidence and Future Directions.

    PubMed

    Slim, Mahmoud; Medina-Caliz, Inmaculada; Gonzalez-Jimenez, Andres; Cabello, M Rosario; Mayoral-Cleries, Fermin; Lucena, M Isabel; Andrade, Raul J

    2016-10-01

    The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs seems improved over that of chlorpromazine, they can occasionally cause idiosyncratic liver injury with varying phenotypes and, rarely, lead to acute liver failure. However, AAPs are a group of heterogeneous, chemically unrelated compounds with distinct pharmacological and pharmacokinetic properties and substantially different safety profiles, which precludes the notion of a class effect for hepatotoxicity risk and highlights the need for an individualized therapeutic approach. We discuss the current evidence on the hepatotoxicity potential of AAPs, the emerging underlying mechanisms, and the limitations inherent to this group of drugs for both establishing a proper causality assessment and developing strategies for risk management.

  17. Direct evidence of an elongation factor-Tu/Ts·GTP·Aminoacyl-tRNA quaternary complex.

    PubMed

    Burnett, Benjamin J; Altman, Roger B; Ferguson, Angelica; Wasserman, Michael R; Zhou, Zhou; Blanchard, Scott C

    2014-08-22

    During protein synthesis, elongation factor-Tu (EF-Tu) bound to GTP chaperones the entry of aminoacyl-tRNA (aa-tRNA) into actively translating ribosomes. In so doing, EF-Tu increases the rate and fidelity of the translation mechanism. Recent evidence suggests that EF-Ts, the guanosine nucleotide exchange factor for EF-Tu, directly accelerates both the formation and dissociation of the EF-Tu-GTP-Phe-tRNA(Phe) ternary complex (Burnett, B. J., Altman, R. B., Ferrao, R., Alejo, J. L., Kaur, N., Kanji, J., and Blanchard, S. C. (2013) J. Biol. Chem. 288, 13917-13928). A central feature of this model is the existence of a quaternary complex of EF-Tu/Ts·GTP·aa-tRNA(aa). Here, through comparative investigations of phenylalanyl, methionyl, and arginyl ternary complexes, and the development of a strategy to monitor their formation and decay using fluorescence resonance energy transfer, we reveal the generality of this newly described EF-Ts function and the first direct evidence of the transient quaternary complex species. These findings suggest that EF-Ts may regulate ternary complex abundance in the cell through mechanisms that are distinct from its guanosine nucleotide exchange factor functions.

  18. Direct Evidence of Egestion and Salivation of Xylella fastidiosa Suggests Sharpshooters Can Be "Flying Syringes".

    PubMed

    Backus, Elaine A; Shugart, Holly J; Rogers, Elizabeth E; Morgan, J Kent; Shatters, Robert

    2015-05-01

    Xylella fastidiosa is unique among insect-transmitted plant pathogens because it is propagative but noncirculative, adhering to and multiplying on the cuticular lining of the anterior foregut. Any inoculation mechanism for X. fastidiosa must explain how bacterial cells exit the vector's stylets via the food canal and directly enter the plant. A combined egestion-salivation mechanism has been proposed to explain these unique features. Egestion is the putative outward flow of fluid from the foregut via hypothesized bidirectional pumping of the cibarium. The present study traced green fluorescent protein-expressing X. fastidiosa or fluorescent nanoparticles acquired from artificial diets by glassy-winged sharpshooters, Homalodisca vitripennis, as they were egested into simultaneously secreted saliva. X. fastidiosa or nanoparticles were shown to mix with gelling saliva to form fluorescent deposits and salivary sheaths on artificial diets, providing the first direct, conclusive evidence of egestion by any hemipteran insect. Therefore, the present results strongly support an egestion-salivation mechanism of X. fastidiosa inoculation. Results also support that a column of fluid is transiently held in the foregut without being swallowed. Evidence also supports (but does not definitively prove) that bacteria were suspended in the column of fluid during the vector's transit from diet to diet, and were egested with the held fluid. Thus, we hypothesize that sharpshooters could be true "flying syringes," especially when inoculation occurs very soon after uptake of bacteria, suggesting the new paradigm of a nonpersistent X. fastidiosa transmission mechanism.

  19. Transcriptionally Regulated Cell Adhesion Network Dictates Distal Tip Cell Directionality

    PubMed Central

    Wong, Ming-Ching; Kennedy, William P.; Schwarzbauer, Jean E.

    2015-01-01

    Background The mechanisms that govern directional changes in cell migration are poorly understood. The migratory paths of two distal tip cells (DTC) determine the U-shape of the C. elegans hermaphroditic gonad. The morphogenesis of this organ provides a model system to identify genes necessary for the DTCs to execute two stereotyped turns. Results Using candidate genes for RNAi knockdown in a DTC-specific strain, we identified two transcriptional regulators required for DTC turning: cbp-1, the CBP/p300 transcriptional coactivator homologue, and let-607, a CREBH transcription factor homologue. Further screening of potential target genes uncovered a network of integrin adhesion-related genes that have roles in turning and are dependent on cbp-1 and let-607 for expression. These genes include src-1/Src kinase, tln-1/talin, pat-2/α integrin and nmy-2, a nonmuscle myosin heavy chain. Conclusions Transcriptional regulation by means of cbp-1 and let-607 is crucial for determining directional changes during DTC migration. These regulators coordinate a gene network that is necessary for integrin-mediated adhesion. Overall, these results suggest that directional changes in cell migration rely on the precise gene regulation of adhesion. PMID:24811939

  20. Direct evidence of the molecular basis for biological silicon transport

    PubMed Central

    Knight, Michael J.; Senior, Laura; Nancolas, Bethany; Ratcliffe, Sarah; Curnow, Paul

    2016-01-01

    Diatoms are an important group of eukaryotic algae with a curious evolutionary innovation: they sheath themselves in a cell wall made largely of silica. The cellular machinery responsible for silicification includes a family of membrane permeases that recognize and actively transport the soluble precursor of biosilica, silicic acid. However, the molecular basis of silicic acid transport remains obscure. Here, we identify experimentally tractable diatom silicic acid transporter (SIT) homologues and study their structure and function in vitro, enabled by the development of a new fluorescence method for studying substrate transport kinetics. We show that recombinant SITs are Na+/silicic acid symporters with a 1:1 protein: substrate stoichiometry and KM for silicic acid of 20 μM. Protein mutagenesis supports the long-standing hypothesis that four conserved GXQ amino acid motifs are important in SIT function. This marks a step towards a detailed understanding of silicon transport with implications for biogeochemistry and bioinspired materials. PMID:27305972

  1. Evidence of Arctic sea ice thinning from direct observations

    NASA Astrophysics Data System (ADS)

    Renner, Angelika H. H.; Gerland, Sebastian; Haas, Christian; Spreen, Gunnar; Beckers, Justin F.; Hansen, Edmond; Nicolaus, Marcel; Goodwin, Harvey

    2014-07-01

    The Arctic sea ice cover is rapidly shrinking, but a direct, longer-term assessment of the ice thinning remains challenging. A new time series constructed from in situ measurements of sea ice thickness at the end of the melt season in Fram Strait shows a thinning by over 50% during 2003-2012. The modal and mean ice thickness along 79°N decreased at a rate of 0.3 and 0.2 m yr-1, respectively, with long-term averages of 2.5 and 3 m. Airborne observations reveal an east-west thickness gradient across the strait in spring but not in summer due to advection from more different source regions. There is no clear relationship between interannual ice thickness variability and the source regions of the ice. The observed thinning is therefore likely a result of Arctic-wide reduction in ice thickness with a potential shift in exported ice types playing a minor role.

  2. Direct evidence of void passivation in Cu(InGa)(SSe){sub 2} absorber layers

    SciTech Connect

    Lee, Dongho; Kim, Young-Su; Mo, Chan B.; Huh, Kwangsoo; Yang, JungYup E-mail: ddang@korea.ac.kr; Nam, Junggyu; Baek, Dohyun; Park, Sungchan; Kim, ByoungJune; Kim, Dongseop; Lee, Jaehan; Heo, Sung; Park, Jong-Bong; Kang, Yoonmook E-mail: ddang@korea.ac.kr

    2015-02-23

    We have investigated the charge collection condition around voids in copper indium gallium sulfur selenide (CIGSSe) solar cells fabricated by sputter and a sequential process of selenization/sulfurization. In this study, we found direct evidence of void passivation by using the junction electron beam induced current method, transmission electron microscopy, and energy dispersive X-ray spectroscopy. The high sulfur concentration at the void surface plays an important role in the performance enhancement of the device. The recombination around voids is effectively suppressed by field-assisted void passivation. Hence, the generated carriers are easily collected by the electrodes. Therefore, when the S/(S + Se) ratio at the void surface is over 8% at room temperature, the device performance degradation caused by the recombination at the voids is negligible at the CIGSSe layer.

  3. Direct evidence of the molecular interaction propagation in the phase transition of liquid crystals

    NASA Astrophysics Data System (ADS)

    Katayama, Kenji; Sato, Takahiro; Kuwahara, Shota

    2016-09-01

    The molecular interaction sometimes propagates in a collective manner, reaching for a long distance on the order of millimeters. Such interactions have been well known in the field of strongly-correlated electron systems in a beautiful crystal interleaved by donor and acceptor layers, induced by photo-stimulus. The other examples can be found in liquid crystals (LCs), which could be found in many places in nature such as bio-membrane. Different from crystals, LCs features "softness", which enables it to be a curved structure such as a cell. In LCs, even a small molecular change would trigger the overall structural change by the propagation of the molecular interaction. Here we will show, for the first time, how long and how fast the molecular interaction propagates in LCs. The patterned phase transition was induced in a LC, causing the phase transition propagation in a controlled way and the propagation was measured with an time-resolved optical technique, called the transient grating. A LC sample doped with azobenzene was put into a thermally controlled LC cell. A grating pattern of a pulse light with 355 nm was impinged to the LC cell, and the light was absorbed by the dyes, releasing heat or photomechanical motion. We could observe the fringe spacing dependence on the phase transition response, which indicates that phase transition was delayed as the fringe spacing due to the delay by the phase transition propagation. This is the first direct evidence of the molecular interaction propagation of the LC molecules.

  4. On the Mechanism of Oxazoline-Directed Metalations: Evidence for Nitrogen-Directed Reactions.

    PubMed

    Sammakia, Tarek; Latham, Hallie A.

    1996-03-08

    We recently described a method for the synthesis of ferrocene complexes possessing planar chirality which relies on the asymmetric deprotonation of chiral ferrocenyloxazolines. The unexpected stereochemical outcome of these reactions led us to examine whether the metalation is directed by the oxygen or the nitrogen of the oxazoline. In this paper, we describe the synthesis of a constrained ferrocenyloxazoline (compound 13) in which oxygen- and nitrogen-directed metalations provide different stereochemical outcomes. Our results show that nitrogen is responsible for the directive effects of the oxazoline when alkyllithium reagents are used to deprotonate the ferrocene. The implications of this result on the origin of asymmetric induction in the metalation of the unconstrained ferrocenyloxazolines 19 and 20 are discussed.

  5. Directional sensitivity of hair cell afferents in the Octopus statocyst.

    PubMed

    Budelmann, B U; Williamson, R

    1994-02-01

    Changes in threshold sensitivity of hair cell afferents of the macula and crista of the Octopus statocyst were analyzed when the hair cells were stimulated with sinusoidal water movements from different directions. The experiments indicate that cephalopod statocyst hair cells are directionally sensitive in a way that is similar to the responses of the hair cells of the vertebrate vestibular and lateral line systems, with the amplitude of the response changing according to the cosine of the angle by which the direction of the stimulus (the deflection of the ciliary bundle) deviates from the direction of the hair cell's morphological polarization.

  6. Laser-based direct-write techniques for cell printing.

    PubMed

    Schiele, Nathan R; Corr, David T; Huang, Yong; Raof, Nurazhani Abdul; Xie, Yubing; Chrisey, Douglas B

    2010-09-01

    Fabrication of cellular constructs with spatial control of cell location (+/-5 microm) is essential to the advancement of a wide range of applications including tissue engineering, stem cell and cancer research. Precise cell placement, especially of multiple cell types in co- or multi-cultures and in three dimensions, can enable research possibilities otherwise impossible, such as the cell-by-cell assembly of complex cellular constructs. Laser-based direct writing, a printing technique first utilized in electronics applications, has been adapted to transfer living cells and other biological materials (e.g., enzymes, proteins and bioceramics). Many different cell types have been printed using laser-based direct writing, and this technique offers significant improvements when compared to conventional cell patterning techniques. The predominance of work to date has not been in application of the technique, but rather focused on demonstrating the ability of direct writing to pattern living cells, in a spatially precise manner, while maintaining cellular viability. This paper reviews laser-based additive direct-write techniques for cell printing, and the various cell types successfully laser direct-written that have applications in tissue engineering, stem cell and cancer research are highlighted. A particular focus is paid to process dynamics modeling and process-induced cell injury during laser-based cell direct writing.

  7. Laser-based direct-write techniques for cell printing

    PubMed Central

    Schiele, Nathan R; Corr, David T; Huang, Yong; Raof, Nurazhani Abdul; Xie, Yubing; Chrisey, Douglas B

    2016-01-01

    Fabrication of cellular constructs with spatial control of cell location (±5 μm) is essential to the advancement of a wide range of applications including tissue engineering, stem cell and cancer research. Precise cell placement, especially of multiple cell types in co- or multi-cultures and in three dimensions, can enable research possibilities otherwise impossible, such as the cell-by-cell assembly of complex cellular constructs. Laser-based direct writing, a printing technique first utilized in electronics applications, has been adapted to transfer living cells and other biological materials (e.g., enzymes, proteins and bioceramics). Many different cell types have been printed using laser-based direct writing, and this technique offers significant improvements when compared to conventional cell patterning techniques. The predominance of work to date has not been in application of the technique, but rather focused on demonstrating the ability of direct writing to pattern living cells, in a spatially precise manner, while maintaining cellular viability. This paper reviews laser-based additive direct-write techniques for cell printing, and the various cell types successfully laser direct-written that have applications in tissue engineering, stem cell and cancer research are highlighted. A particular focus is paid to process dynamics modeling and process-induced cell injury during laser-based cell direct writing. PMID:20814088

  8. CD4(+) Th2 cells are directly regulated by IL-10 during allergic airway inflammation.

    PubMed

    Coomes, S M; Kannan, Y; Pelly, V S; Entwistle, L J; Guidi, R; Perez-Lloret, J; Nikolov, N; Müller, W; Wilson, M S

    2017-01-01

    Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4(+) Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.

  9. Sea urchin elongation factor 1delta (EF1delta) and evidence for cell cycle-directed localization changes of a sub-fraction of the protein at M phase.

    PubMed

    Boulben, S; Monnier, A; Le Breton, M; Morales, J; Cormier, P; Bellé, R; Mulner-Lorillon, O

    2003-10-01

    Eukaryotic elongation factor 1 (eEF1) is a translational multimolecular complex reported in higher eukaryotes to be a target of CDK1/cyclin B, the universal regulator of M phase, but whose role in the cell cycle remains to be determined. A specific polyclonal antibody was produced and used to characterize the delta subunit of sea urchin elongation factor 1 (SgEF1delta) in early embryos, a powerful model for investigating cell cycle regulation. The SgEF1delta protein was present in unfertilized eggs as two isoforms of 35 and 37 kDa, issued from two different mRNAs. The two canonical eEF1delta partners, eEF1gamma and eEF1beta, were shown to co-immunoprecipitate with the SgEF1delta isoforms. Both isoforms were associated in a macromolecular complex, which resolved upon gel filtration chromatography at a molecular weight > 400 kDa, suggesting association with other yet unidentified partners. After fertilization, the amount as well as the ratio of both SgEF1delta isoforms remained constant during the first cell division as judged by Western blotting. Immunofluorescence analysis showed that a pool of the protein concentrated as a ring at the embryo nuclear location around the period of nuclear envelope breakdown and was visualized later as two large spheres around the mitotic spindle poles. Thus, the eEF1delta protein shows cell cycle-specific localization changes in sea urchin embryos.

  10. Direct reprogramming and biomaterials for controlling cell fate.

    PubMed

    Kim, Eunsol; Tae, Giyoong

    2016-01-01

    Direct reprogramming which changes the fate of matured cell is a very useful technique with a great interest recently. This approach can eliminate the drawbacks of direct usage of stem cells and allow the patient specific treatment in regenerative medicine. Overexpression of diverse factors such as general reprogramming factors or lineage specific transcription factors can change the fate of already differentiated cells. On the other hand, biomaterials can provide physical and topographical cues or biochemical cues on cells, which can dictate or significantly affect the differentiation of stem cells. The role of biomaterials on direct reprogramming has not been elucidated much, but will be potentially significant to improve the efficiency or specificity of direct reprogramming. In this review, the strategies for general direct reprogramming and biomaterials-guided stem cell differentiation are summarized with the addition of the up-to-date progress on biomaterials for direct reprogramming.

  11. Direction-Setting School Leadership Practices: A Meta-Analytical Review of Evidence about Their Influence

    ERIC Educational Resources Information Center

    Sun, Jingping; Leithwood, Kenneth

    2015-01-01

    This study reviews evidence about the overall influence of direction-setting leadership practices (DSLPs), 1 of 4 major categories of practices included in a widely known conception of effective leadership (e.g., Leithwood & Louis, 2011) and a focus of many other such conceptions, as well. This study also inquires about how direction-setting…

  12. Direct evidence that PKCα positively regulates wound re-epithelialization: correlation with changes in desmosomal adhesiveness.

    PubMed

    Thomason, Helen A; Cooper, Nichola H; Ansell, David M; Chiu, Maybo; Merrit, Anita J; Hardman, Matthew J; Garrod, David R

    2012-07-01

    Non-healing wounds cause considerable patient morbidity and represent a significant economic burden. Central to wound repair is re-epithelialization, a crucial process involving the modulation of cell adhesion to allow keratinocyte migration to cover the exposed underlying tissues. The cellular mechanisms regulating the earliest stages of re-epithelialization are unclear. We present the first direct evidence that protein kinase Cα (PKCα) plays an important role in regulating wound re-epithelialization. In PKCα(-/-) mice re-epithelialization is delayed, while in novel bitransgenic mice over-expressing constitutively active PKCα it is accelerated. These effects are not due to changes in keratinocyte proliferation, apoptosis or intrinsic cell motility. Instead, they correlate with changes in desmosomal adhesiveness, delay being preceded by retained desmosomal hyper-adhesiveness and acceleration with a rapid switch to desmosomal Ca(2+) -dependence. We demonstrate mechanistic conservation in acute human wounds where PKCα localizes to wound edge desmosomes, which become Ca(2+) -dependent. However, in chronic wounds PKCα remains cytoplasmic and desmosomes fail to switch from the hyper-adhesive state. These results throw new mechanistic light on the earliest stages of wound re-epithelialization and suggest activation of PKCα as a new therapeutic strategy for non-healing wounds.

  13. Evidence for Human Lung Stem Cells

    PubMed Central

    Kajstura, Jan; Rota, Marcello; Hall, Sean R.; Hosoda, Toru; D’Amario, Domenico; Sanada, Fumihiro; Zheng, Hanqiao; Ogórek, Barbara; Rondon-Clavo, Carlos; Ferreira-Martins, João; Matsuda, Alex; Arranto, Christian; Goichberg, Polina; Giordano, Giovanna; Haley, Kathleen J.; Bardelli, Silvana; Rayatzadeh, Hussein; Liu, Xiaoli; Quaini, Federico; Liao, Ronglih; Leri, Annarosa; Perrella, Mark A.; Loscalzo, Joseph; Anversa, Piero

    2011-01-01

    BACKGROUND Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive. METHODS Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo. RESULTS Human lungs contain undifferentiated human lung stem cells nested in niches in the distal airways. These cells are self-renewing, clonogenic, and multipotent in vitro. After injection into damaged mouse lung in vivo, human lung stem cells form human bronchioles, alveoli, and pulmonary vessels integrated structurally and functionally with the damaged organ. The formation of a chimeric lung was confirmed by detection of human transcripts for epithelial and vascular genes. In addition, the self-renewal and long-term proliferation of human lung stem cells was shown in serial-transplantation assays. CONCLUSIONS Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease. (Funded by the National Institutes of Health.) PMID:21561345

  14. Direct methanol feed fuel cell and system

    NASA Technical Reports Server (NTRS)

    Surampudi, Subbarao (Inventor); Frank, Harvey A. (Inventor); Narayanan, Sekharipuram R. (Inventor); Chun, William (Inventor); Jeffries-Nakamura, Barbara (Inventor); Kindler, Andrew (Inventor); Halpert, Gerald (Inventor)

    2009-01-01

    Improvements to non acid methanol fuel cells include new formulations for materials. The platinum and ruthenium are more exactly mixed together. Different materials are substituted for these materials. The backing material for the fuel cell electrode is specially treated to improve its characteristics. A special sputtered electrode is formed which is extremely porous. The fuel cell system also comprises a fuel supplying part including a meter which meters an amount of fuel which is used by the fuel cell, and controls the supply of fuel based on said metering.

  15. Direct Methanol Fuel Cell (DMFC) Battery Replacement Program

    DTIC Science & Technology

    2013-01-29

    studies on performance degradation of Catalysts and Nafion™ Membrane Functional Groups in Direct Methanol Fuel Cells, IN PREP (06 2013) TOTAL: 1 Books... 18 Single Cell: Progress...31 Laser Activated Membrane Introduction Mass Spectrometry (LAMIMS) .................................... 37 Future Work (internally

  16. Direct methanol feed fuel cell and system

    NASA Technical Reports Server (NTRS)

    Surampudi, Subbarao (Inventor); Frank, Harvey A. (Inventor); Narayanan, Sekharipuram R. (Inventor); Chun, William (Inventor); Jeffries-Nakamura, Barbara (Inventor); Kindler, Andrew (Inventor); Halpert, Gerald (Inventor)

    2004-01-01

    Improvements to non acid methanol fuel cells include new formulations for materials. The platinum and ruthenium are more exactly mixed together. Different materials are substituted for these materials. The backing material for the fuel cell electrode is specially treated to improve its characteristics. A special sputtered electrode is formed which is extremely porous.

  17. Direct methanol feed fuel cell and system

    NASA Technical Reports Server (NTRS)

    Surampudi, Subbarao (Inventor); Frank, Harvey A. (Inventor); Narayanan, Sekharipuram R. (Inventor); Chun, William (Inventor); Jeffries-Nakamura, Barbara (Inventor); Kindler, Andrew (Inventor); Halpert, Gerald (Inventor)

    2008-01-01

    Improvements to non acid methanol fuel cells include new formulations for materials. The platinum and ruthenium are more exactly mixed together. Different materials are substituted for these materials. The backing material for the fuel cell electrode is specially treated to improve its characteristics. A special sputtered electrode is formed which is extremely porous.

  18. Direct methanol feed fuel cell and system

    NASA Technical Reports Server (NTRS)

    Surampudi, Subbarao (Inventor); Frank, Harvey A. (Inventor); Narayanan, Sekharipuram R. (Inventor); Chun, William (Inventor); Jeffries-Nakamura, Barbara (Inventor); Kindler, Andrew (Inventor); Halpert, Gerald (Inventor)

    2001-01-01

    Improvements to non acid methanol fuel cells include new formulations for materials. The platinum and ruthenium are more exactly mixed together. Different materials are substituted for these materials. The backing material for the fuel cell electrode is specially treated to improve its characteristics. A special sputtered electrode is formed which is extremely porous.

  19. Direct methanol feed fuel cell and system

    NASA Technical Reports Server (NTRS)

    Surampudi, Subbarao (Inventor); Frank, Harvey A. (Inventor); Narayanan, Sekharipuram R. (Inventor); Chun, William (Inventor); Jeffries-Nakamura, Barbara (Inventor); Kindler, Andrew (Inventor); Halpert, Gerald (Inventor)

    2000-01-01

    Improvements to non-acid methanol fuel cells include new formulations for materials. The platinum and ruthenium are more exactly mixed together. Different materials are substituted for these materials. The backing material for the fuel cell electrode is specially treated to improve its characteristics. A special sputtered electrode is formed which is extremely porous.

  20. Aerosol feed direct methanol fuel cell

    NASA Technical Reports Server (NTRS)

    Kindler, Andrew (Inventor); Narayanan, Sekharipuram R. (Inventor); Valdez, Thomas I. (Inventor)

    2002-01-01

    Improvements to fuel cells include introduction of the fuel as an aerosol of liquid fuel droplets suspended in a gas. The particle size of the liquid fuel droplets may be controlled for optimal fuel cell performance by selection of different aerosol generators or by separating droplets based upon size using a particle size conditioner.

  1. Directional cell movement through tissues is controlled by exosome secretion

    PubMed Central

    Sung, Bong Hwan; Ketova, Tatiana; Hoshino, Daisuke; Zijlstra, Andries; Weaver, Alissa M.

    2015-01-01

    Directional cell movement through tissues is critical for multiple biological processes and requires maintenance of polarity in the face of complex environmental cues. Here we use intravital imaging to demonstrate that secretion of exosomes from late endosomes is required for directionally persistent and efficient in vivo movement of cancer cells. Inhibiting exosome secretion or biogenesis leads to defective tumour cell migration associated with increased formation of unstable protrusions and excessive directional switching. In vitro rescue experiments with purified exosomes and matrix coating identify adhesion assembly as a critical exosome function that promotes efficient cell motility. Live-cell imaging reveals that exosome secretion directly precedes and promotes adhesion assembly. Fibronectin is found to be a critical motility-promoting cargo whose sorting into exosomes depends on binding to integrins. We propose that autocrine secretion of exosomes powerfully promotes directionally persistent and effective cell motility by reinforcing otherwise transient polarization states and promoting adhesion assembly. PMID:25968605

  2. Electric field-directed fibroblast locomotion involves cell surface molecular reorganization and is calcium independent

    PubMed Central

    1994-01-01

    Directional cellular locomotion is thought to involve localized intracellular calcium changes and the lateral transport of cell surface molecules. We have examined the roles of both calcium and cell surface glycoprotein redistribution in the directional migration of two murine fibroblastic cell lines, NIH 3T3 and SV101. These cell types exhibit persistent, cathode directed motility when exposed to direct current electric fields. Using time lapse phase contrast microscopy and image analysis, we have determined that electric field-directed locomotion in each cell type is a calcium independent process. Both exhibit cathode directed motility in the absence of extracellular calcium, and electric fields cause no detectable elevations or gradients of cytosolic free calcium. We find evidence suggesting that galvanotaxis in these cells involves the lateral redistribution of plasma membrane glycoproteins. Electric fields cause the lateral migration of plasma membrane concanavalin A receptors toward the cathode in both NIH 3T3 and SV101 fibroblasts. Exposure of directionally migrating cells to Con A inhibits the normal change of cell direction following a reversal of electric field polarity. Additionally, when cells are plated on Con A- coated substrata so that Con A receptors mediate cell-substratum adhesion, cathode-directed locomotion and a cathodal accumulation of Con A receptors are observed. Immunofluorescent labeling of the fibronectin receptor in NIH 3T3 fibroblasts suggests the recruitment of integrins from large clusters to form a more diffuse distribution toward the cathode in field-treated cells. Our results indicate that the mechanism of electric field directed locomotion in NIH 3T3 and SV101 fibroblasts involves the lateral redistribution of plasma membrane glycoproteins involved in cell-substratum adhesion. PMID:7929557

  3. DIRECT AMMONIA-AIR FUEL CELL.

    DTIC Science & Technology

    fuel cell was investigated. This cell is based on the use of a non-aqueous fused hydroxide electrolyte matrix, and operates in the intermediate temperature range of 180-300 C. Studies have been carried out to determine the nature of the ratecontrolling step in the kinetics of the anodic oxidation of ammonia. A new type of Ni/NiOOH reference electrode was developed for the measurement of single electrode potentials in experimental galvanic fuel cells employing this type of matrix electrolyte. In addition to various exploratory studies, two statistical analysis

  4. Evidence-based arguments in direct democracy: The case of smoking bans in Switzerland.

    PubMed

    Stucki, Iris

    2016-08-31

    This article analyses the use of evidence, such as policy evaluation studies, in arguments in direct-democratic campaigns. Set in the context of 16 Swiss direct-democratic campaigns on smoking bans, the article compares evidence-based arguments with arguments that do not refer to evidence. The study adds to the argumentative direction in evaluation and program planning by showing that in direct-democratic campaigns, the political use of evaluation results to substantiate policy preferences is rare. The study shows that around 6% of the arguments refer to evidence and that evaluation results are mostly cited in support of causal arguments referring to the effects of policy interventions. Above all, the results show that policy information is available, at least for causal arguments, and apparently known in the public discourse but only cited explicitly when the speaker wants to raise credibility. This applies especially to researchers, such as evaluators. The results further indicate that the political use of evaluation results fosters an informed discourse and the evidence may eventually become common public knowledge. The credentials of evaluators make them suitable not only for bringing more evaluation results into the direct-democratic discourse but also for acting as teachers in this discourse.

  5. Direct-Write Contacts for Solar Cells

    SciTech Connect

    Kaydanova, T.; van Hest, M.F.A.M.; Miedaner, A.; Curtis, C. J.; Alleman, J. L.; Dabney, M. S.; Garnett, E.; Shaheen, S.; Ginley, D. S.; Smith, L.; Collins, R.; Hanoka, J. I.; Gabor, A. M.

    2005-01-01

    We report on our project to develop inkjet printable contacts for solar cells. Ag, Cu, and Ni metallizations were inkjet printed with near vacuum deposition quality. Thick, highly conducting lines of Ag and Cu demonstrating good adhesion to glass, Si, and PCB have been printed at 100-200 C in air and N2, respectively. Ag grids were inkjet-printed on Si solar cells and fired through silicon nitride AR layer at 850 C resulting in 8% cells. Next-generation multicomponent inks (including etching agents) have also been developed with improved fire-through contacts leading to higher cell efficiencies. The approach developed can be easily extended to other conductors such as Pt, Pd, and Au, etc. In addition, PEDOT-PSS polymer-based conductors were inkjet-printed with the conductivity as good or better than those of polymer-based conductors.

  6. The irregular firing properties of thalamic head direction cells mediate turn-specific modulation of the directional tuning curve

    PubMed Central

    Tsanov, Marian; Chah, Ehsan; Noor, Muhammad S.; Egan, Catriona; Reilly, Richard B.; Aggleton, John P.; Erichsen, Jonathan T.; Vann, Seralynne D.

    2014-01-01

    Head direction cells encode an animal's heading in the horizontal plane. However, it is not clear why the directionality of a cell's mean firing rate differs for clockwise, compared with counterclockwise, head turns (this difference is known as the “separation angle”) in anterior thalamus. Here we investigated in freely behaving rats whether intrinsic neuronal firing properties are linked to this phenomenon. We found a positive correlation between the separation angle and the spiking variability of thalamic head direction cells. To test whether this link is driven by hyperpolarization-inducing currents, we investigated the effect of thalamic reticular inhibition during high-voltage spindles on directional spiking. While the selective directional firing of thalamic neurons was preserved, we found no evidence for entrainment of thalamic head direction cells by high-voltage spindle oscillations. We then examined the role of depolarization-inducing currents in the formation of separation angle. Using a single-compartment Hodgkin-Huxley model, we show that modeled neurons fire with higher frequencies during the ascending phase of sinusoidal current injection (mimicking the head direction tuning curve) when simulated with higher high-threshold calcium channel conductance. These findings demonstrate that the turn-specific encoding of directional signal strongly depends on the ability of thalamic neurons to fire irregularly in response to sinusoidal excitatory activation. Another crucial factor for inducing phase lead to sinusoidal current injection was the presence of spike-frequency adaptation current in the modeled neurons. Our data support a model in which intrinsic biophysical properties of thalamic neurons mediate the physiological encoding of directional information. PMID:25122712

  7. Direct Write Contacts for Solar Cells

    SciTech Connect

    Kaydanova, T.; van Hest, M.F.A.M.; Miedaner, A.; Curtis, C. J.; Alleman, J. L.; Dabney, M. S.; Garnett, E.; Shaheen, S.; Smith, L.; Collins, R.; Hanoka, J. I.; Gabor, A. M.; Ginley, D.S.

    2005-02-01

    Ag, Cu, and Ni metallizations were inkjet-printed with near-vacuum deposition quality. The approach developed can be easily extended to other conductors such as Pt, Pd, and Au. Thick, highly conducting lines of Ag and Cu demonstrating good adhesion to glass, Si, and PCB have been printed at 100-200 C in air and N2, respectively. Ag grids were inkjet-printed on Si solar cells and fired through the silicon nitride antireflective layer at 850 C resulting in 8%-efficient cells. Next-generation multicomponent inks (including etching agents) have also been developed with improved fire-through contacts leading to higher cell efficiencies. PEDOT-PSS polymer-based conductors were inkjet-printed with conductivity as good or better than that of spin-coated films.

  8. Stromal Cell Subsets Directing Neonatal Spleen Regeneration

    PubMed Central

    Tan, Jonathan K. H.; Watanabe, Takeshi

    2017-01-01

    Development of lymphoid tissue is determined by interactions between stromal lymphoid tissue organiser (LTo) and hematopoietic lymphoid tissue inducer (LTi) cells. A failure for LTo to receive appropriate activating signals during embryogenesis through lymphotoxin engagement leads to a complete cessation of lymph node (LN) and Peyer’s patch development, identifying LTo as a key stromal population for lymphoid tissue organogenesis. However, little is known about the equivalent stromal cells that induce spleen development. Here, by dissociating neonatal murine spleen stromal tissue for re-aggregation and transplant into adult mouse recipients, we have identified a MAdCAM-1+CD31+CD201+ spleen stromal organizer cell-type critical for new tissue formation. This finding provides an insight into the regulation of post-natal spleen tissue organogenesis, and could be exploited in the development of spleen regenerative therapies. PMID:28067323

  9. Single cell activity reveals direct electron transfer in methanotrophic consortia

    NASA Astrophysics Data System (ADS)

    McGlynn, Shawn E.; Chadwick, Grayson L.; Kempes, Christopher P.; Orphan, Victoria J.

    2015-10-01

    Multicellular assemblages of microorganisms are ubiquitous in nature, and the proximity afforded by aggregation is thought to permit intercellular metabolic coupling that can accommodate otherwise unfavourable reactions. Consortia of methane-oxidizing archaea and sulphate-reducing bacteria are a well-known environmental example of microbial co-aggregation; however, the coupling mechanisms between these paired organisms is not well understood, despite the attention given them because of the global significance of anaerobic methane oxidation. Here we examined the influence of interspecies spatial positioning as it relates to biosynthetic activity within structurally diverse uncultured methane-oxidizing consortia by measuring stable isotope incorporation for individual archaeal and bacterial cells to constrain their potential metabolic interactions. In contrast to conventional models of syntrophy based on the passage of molecular intermediates, cellular activities were found to be independent of both species intermixing and distance between syntrophic partners within consortia. A generalized model of electric conductivity between co-associated archaea and bacteria best fit the empirical data. Combined with the detection of large multi-haem cytochromes in the genomes of methanotrophic archaea and the demonstration of redox-dependent staining of the matrix between cells in consortia, these results provide evidence for syntrophic coupling through direct electron transfer.

  10. New directions in InP solar cell research

    NASA Technical Reports Server (NTRS)

    Weinberg, I.; Swartz, C. K.; Brinker, D. J.

    1990-01-01

    Recent research efforts representing new directions in InP solar cell research are reviewed. These include heteroepitaxial growth on silicon and gallium arsenide substrates, V-grooved cells, large area high efficiency cells, and surface passivation. Improvements in heteroepitaxial cell efficiency are described together with processing of 19.1 percent, 4 sq cm cells. Recommendations are made for improvements in processing leading to increased efficiencies.

  11. Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration.

    PubMed

    Richardson, Jo; Gauert, Anton; Briones Montecinos, Luis; Fanlo, Lucía; Alhashem, Zainalabdeen Mohmammed; Assar, Rodrigo; Marti, Elisa; Kabla, Alexandre; Härtel, Steffen; Linker, Claudia

    2016-05-31

    Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC) cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC) cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC) cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.

  12. Gammaherpesviruses and canine lymphoma: no evidence for direct involvement in commonly occurring lymphomas.

    PubMed

    Waugh, Elspeth M; Gallagher, Alice; McAulay, Karen A; Henriques, Joaquim; Alves, Margarida; Bell, Adam J; Morris, Joanna S; Jarrett, Ruth F

    2015-07-01

    Lymphoma is the most common haematopoietic malignancy in dogs, but little is known about the aetiology of this heterogeneous group of cancers. In humans, the Epstein-Barr virus (EBV) is associated with several lymphoma subtypes. Recently, it was suggested that EBV or an EBV-like virus is circulating in dogs. We therefore investigated whether EBV, or a novel herpesvirus, is associated with canine lymphoma using both serological and molecular techniques. In an assay designed to detect antibodies to EBV viral capsid antigens, 41 % of dogs were positive. Dogs with cancers, including lymphoma, were more frequently positive than controls, but no particular association with B-cell lymphoma was noted. EBV-specific RNA and DNA sequences were not detected in lymphoma tissue by in situ hybridization or PCR, and herpesvirus genomes were not detected using multiple degenerate PCR assays with the ability to detect novel herpesviruses. We therefore found no evidence that herpesviruses are directly involved in common types of canine lymphoma although cannot exclude the presence of an EBV-like virus in the canine population.

  13. Direct evidence that two cysteines in the dopamine transporter form a disulfide bond.

    PubMed

    Chen, Rong; Wei, Hua; Hill, Erik R; Chen, Lucy; Jiang, Liying; Han, Dawn D; Gu, Howard H

    2007-04-01

    We have generated a fully functional dopamine transporter (DAT) mutant (dmDATx7) with all cysteines removed except the two cysteines in extracellular loop 2 (EL2). Random mutagenesis at either or both EL2 cysteines did not produce any functional transporter mutants, suggesting that the two cysteines cannot be replaced by any other amino acids. The cysteine-specific reagent MTSEA-biotin labeled dmDATx7 only after a DTT treatment which reduces disulfide bond. Since there are no other cysteines in dmDATx7, the MTSEA-biotin labeling must be on the EL2 cysteines made available by the DTT treatment. This result provides the first direct evidence that the EL2 cysteines form a disulfide bond. Interestingly, the DTT treatment had little effect on transport activity suggesting that the disulfide bond is not necessary for the uptake function of DAT. Our results and previous results are consistent with the notion that the disulfide bond between EL2 cysteines is required for DAT biosynthesis and/or its delivery to the cell surface.

  14. Gammaherpesviruses and canine lymphoma: no evidence for direct involvement in commonly occurring lymphomas

    PubMed Central

    Gallagher, Alice; McAulay, Karen A.; Henriques, Joaquim; Alves, Margarida; Bell, Adam J.; Morris, Joanna S.; Jarrett, Ruth F.

    2015-01-01

    Lymphoma is the most common haematopoietic malignancy in dogs, but little is known about the aetiology of this heterogeneous group of cancers. In humans, the Epstein–Barr virus (EBV) is associated with several lymphoma subtypes. Recently, it was suggested that EBV or an EBV-like virus is circulating in dogs. We therefore investigated whether EBV, or a novel herpesvirus, is associated with canine lymphoma using both serological and molecular techniques. In an assay designed to detect antibodies to EBV viral capsid antigens, 41 % of dogs were positive. Dogs with cancers, including lymphoma, were more frequently positive than controls, but no particular association with B-cell lymphoma was noted. EBV-specific RNA and DNA sequences were not detected in lymphoma tissue by in situ hybridization or PCR, and herpesvirus genomes were not detected using multiple degenerate PCR assays with the ability to detect novel herpesviruses. We therefore found no evidence that herpesviruses are directly involved in common types of canine lymphoma although cannot exclude the presence of an EBV-like virus in the canine population. PMID:25722346

  15. The innate immune protein Nod2 binds directly to MDP, a bacterial cell wall fragment.

    PubMed

    Grimes, Catherine Leimkuhler; Ariyananda, Lushanti De Zoysa; Melnyk, James E; O'Shea, Erin K

    2012-08-22

    Mammalian Nod2 is an intracellular protein that is implicated in the innate immune response to the bacterial cell wall and is associated with the development of Crohn's disease, Blau syndrome, and gastrointestinal cancers. Nod2 is required for an immune response to muramyl dipeptide (MDP), an immunostimulatory fragment of bacterial cell wall, but it is not known whether MDP binds directly to Nod2. We report the expression and purification of human Nod2 from insect cells. Using novel MDP self-assembled monolayers (SAMs), we provide the first biochemical evidence for a direct, high-affinity interaction between Nod2 and MDP.

  16. Electron-beam direct processing on living cell membrane

    SciTech Connect

    Hoshino, Takayuki; Morishima, Keisuke

    2011-10-24

    We demonstrated a direct processing on a living Hep G2 cell membrane in conventional cultivation conditions using an electron beam. Electron beam-induced deposition from liquid precursor 3,4-ethylenedioxythiophene and ablation was performed on the living cells. The 2.5-10 keV electron beam which was irradiated through a 100-nm-thick SiN nanomembrane could induce a deposition pattern and a ablation on a living cell membrane. This electron beam direct processing can provide simple in-situ cell surface modification for an analytical method of living cell membrane dynamic.

  17. Evidence for G-quadruplex DNA in human cells.

    PubMed

    Xu, Yan; Komiyama, Makoto

    2013-05-27

    Seen in human cells: A fluorochrome-labeled antibody probe selectively and efficiently binds all types of DNA G-quadruplex with similar binding affinities, but hardly binds single- or double-stranded DNA, or RNA hairpins. Thus, this antibody strictly discriminates between G-quadruplex structures and other conformations of DNA and provides evidence for G-quadruplex DNA in human cells.

  18. Perceived azimuth direction is exaggerated: Converging evidence from explicit and implicit measures

    PubMed Central

    Li, Zhi; Durgin, Frank H.

    2016-01-01

    Recent observations suggest that perceived visual direction in the sagittal plane (angular direction in elevation, both upward and downward from eye level) is exaggerated. Foley, Ribeiro-Filho, and Da Silva's (2004) study of perceived size of exocentric ground extent implies that perceived angular direction in azimuth may also be exaggerated. In the present study, we directly examined whether perceived azimuth direction is overestimated. In Experiment 1, numeric estimates of azimuth direction (−48° to 48° relative to straight ahead) were obtained. The results showed a linear exaggeration in perceived azimuth direction with a gain of about 1.26. In Experiment 2, a perceptual extent-matching task served as an implicit measure of perceived azimuth direction. Participants matched an egocentric distance in one direction to a frontal extent in nearly the opposite direction. The angular biases implied by the matching data well replicated Foley et al.'s finding and were also fairly consistent with the azimuth bias function found in Experiment 1, although a slight overall shift was observed between the results of the two experiments. Experiment 3, in which half the observers were tilted sideways while making frontal/depth extent comparisons, suggested that the discrepancy between the results of Experiment 1 and 2 can partially be explained by a retinal horizontal vertical illusion affecting distance estimation tasks. Overall the present study provides converging evidence to suggest that the perception of azimuth direction is overestimated. PMID:26756174

  19. Encoding of head direction by hippocampal place cells in bats.

    PubMed

    Rubin, Alon; Yartsev, Michael M; Ulanovsky, Nachum

    2014-01-15

    Most theories of navigation rely on the concept of a mental map and compass. Hippocampal place cells are neurons thought to be important for representing the mental map; these neurons become active when the animal traverses a specific location in the environment (the "place field"). Head-direction cells are found outside the hippocampus, and encode the animal's head orientation, thus implementing a neural compass. The prevailing view is that the activity of head-direction cells is not tuned to a single place, while place cells do not encode head direction. However, little work has been done to investigate in detail the possible head-directional tuning of hippocampal place cells across species. Here we addressed this by recording the activity of single neurons in the hippocampus of two evolutionarily distant bat species, Egyptian fruit bat and big brown bat, which crawled randomly in three different open-field arenas. We found that a large fraction of hippocampal neurons, in both bat species, showed conjunctive sensitivity to the animal's spatial position (place field) and to its head direction. We introduced analytical methods to demonstrate that the head-direction tuning was significant even after controlling for the behavioral coupling between position and head direction. Surprisingly, some hippocampal neurons preserved their head direction tuning even outside the neuron's place field, suggesting that "spontaneous" extra-field spikes are not noise, but in fact carry head-direction information. Overall, these findings suggest that bat hippocampal neurons can convey both map information and compass information.

  20. Evidence-Based Youth Psychotherapies Versus Usual Clinical Care: A Meta-Analysis of Direct Comparisons

    ERIC Educational Resources Information Center

    Weisz, John R.; Jensen-Doss, Amanda; Hawley, Kristin M.

    2006-01-01

    In the debate over evidence-based treatments (EBTs) for youth, one question is central: Do EBTs produce better outcomes than the usual interventions employed in clinical care? The authors addressed this question through a meta-analysis of 32 randomized trials that directly compared EBTs with usual care. EBTs outperformed usual care. Effects fell…

  1. Distractor Devaluation Effect in the Attentional Blink: Direct Evidence for Distractor Inhibition

    ERIC Educational Resources Information Center

    Kihara, Ken; Yagi, Yoshihiko; Takeda, Yuji; Kawahara, Jun I.

    2011-01-01

    When two targets (T1 and T2) are embedded in rapid serial visual presentation (RSVP), T2 is often missed (attentional blink, AB) if T2 follows T1 by less than 500 ms. Some have proposed that inhibition of a distractor following T1 contributes to the AB, but no direct evidence supports this proposal. This study examined distractor inhibition by…

  2. New directions in evidence-based policy research: a critical analysis of the literature.

    PubMed

    Oliver, Kathryn; Lorenc, Theo; Innvær, Simon

    2014-07-14

    Despite 40 years of research into evidence-based policy (EBP) and a continued drive from both policymakers and researchers to increase research uptake in policy, barriers to the use of evidence are persistently identified in the literature. However, it is not clear what explains this persistence - whether they represent real factors, or if they are artefacts of approaches used to study EBP. Based on an updated review, this paper analyses this literature to explain persistent barriers and facilitators. We critically describe the literature in terms of its theoretical underpinnings, definitions of 'evidence', methods, and underlying assumptions of research in the field, and aim to illuminate the EBP discourse by comparison with approaches from other fields. Much of the research in this area is theoretically naive, focusing primarily on the uptake of research evidence as opposed to evidence defined more broadly, and privileging academics' research priorities over those of policymakers. Little empirical data analysing the processes or impact of evidence use in policy is available to inform researchers or decision-makers. EBP research often assumes that policymakers do not use evidence and that more evidence - meaning research evidence - use would benefit policymakers and populations. We argue that these assumptions are unsupported, biasing much of EBP research. The agenda of 'getting evidence into policy' has side-lined the empirical description and analysis of how research and policy actually interact in vivo. Rather than asking how research evidence can be made more influential, academics should aim to understand what influences and constitutes policy, and produce more critically and theoretically informed studies of decision-making. We question the main assumptions made by EBP researchers, explore the implications of doing so, and propose new directions for EBP research, and health policy.

  3. Direct methanol fuel cell and system

    DOEpatents

    Wilson, Mahlon S.

    2004-10-26

    A fuel cell having an anode and a cathode and a polymer electrolyte membrane located between anode and cathode gas diffusion backings uses a methanol vapor fuel supply. A permeable polymer electrolyte membrane having a permeability effective to sustain a carbon dioxide flux equivalent to at least 10 mA/cm.sup.2 provides for removal of carbon dioxide produced at the anode by reaction of methanol with water. Another aspect of the present invention includes a superabsorpent polymer material placed in proximity to the anode gas diffusion backing to hold liquid methanol or liquid methanol solution without wetting the anode gas diffusion backing so that methanol vapor from the liquid methanol or liquid methanol-water solution is supplied to the membrane.

  4. DIRECT FUEL CELL/TURBINE POWER PLANT

    SciTech Connect

    Hossein Ghezel-Ayagh

    2003-05-27

    The subMW hybrid DFC/T power plant facility was upgraded with a Capstone C60 microturbine and a state-of-the-art full size fuel cell stack. The integration of the larger microturbine extended the capability of the hybrid power plant to operate at high power ratings with a single gas turbine without the need for supplementary air. The objectives of this phase of subMW hybrid power plant tests are to support the development of process and control and to provide the insight for the design of the packaged subMW hybrid demonstration units. The development of the ultra high efficiency multi-MW power plants was focused on the design of 40 MW power plants with efficiencies approaching 75% (LHV of natural gas). The design efforts included thermodynamic cycle analysis of key gas turbine parameters such as compression ratio.

  5. Direct deposit of catalyst on the membrane of direct feed fuel cells

    NASA Technical Reports Server (NTRS)

    Chun, William (Inventor); Narayanan, Sekharipuram R. (Inventor); Jeffries-Nakamura, Barbara (Inventor); Valdez, Thomas I. (Inventor); Linke, Juergen (Inventor)

    2001-01-01

    An improved direct liquid-feed fuel cell having a solid membrane electrolyte for electrochemical reactions of an organic fuel. Catalyst utilization and catalyst/membrane interface improvements are disclosed. Specifically, the catalyst layer is applied directly onto the membrane electrolyte.

  6. Controlling mechanisms in directional growth of aggregated archaeal cells.

    PubMed

    Milkevych, Viktor; Batstone, Damien J

    2014-12-28

    Members of the family Methanosarcinaceae are important archaeal representatives due to their broad functionality, ubiquitous presence, and functionality in harsh environments. A key characteristic is their multicellular (packet) morphology represented by aggregates of spatially confined cells. This morphology is driven by directed growth of cells in confinement with sequential variation in growth direction. To further understand why spatially confined Methanosarcina cells (and in general, confined prokaryotes) change their direction of growth during consecutive growth-division stages, and how a particular cell senses its wall topology and responds to changes on it a theoretical model for stress dependent growth of aggregated archaeal cells was developed. The model utilizes a confined elastic shell representation of aggregated archaeal cell and is derived based on a work-energy principle. The growth law takes into account the fine structure of archaeal cell wall, polymeric nature of methanochondroitin layer, molecular-biochemical processes and is based on thermodynamic laws. The developed model has been applied to three typical configurations of aggregated cell in 3D. The developed model predicted a geometry response with delayed growth of aggregated archaeal cells explained from mechanistic principles, as well as continuous changes in direction of growth during the consecutive growth-division stages. This means that cell wall topology sensing and growth anisotropy can be predicted using simple cellular mechanisms without the need for dedicated cellular machinery.

  7. New directions in evidence-based policy research: a critical analysis of the literature

    PubMed Central

    2014-01-01

    Despite 40 years of research into evidence-based policy (EBP) and a continued drive from both policymakers and researchers to increase research uptake in policy, barriers to the use of evidence are persistently identified in the literature. However, it is not clear what explains this persistence – whether they represent real factors, or if they are artefacts of approaches used to study EBP. Based on an updated review, this paper analyses this literature to explain persistent barriers and facilitators. We critically describe the literature in terms of its theoretical underpinnings, definitions of ‘evidence’, methods, and underlying assumptions of research in the field, and aim to illuminate the EBP discourse by comparison with approaches from other fields. Much of the research in this area is theoretically naive, focusing primarily on the uptake of research evidence as opposed to evidence defined more broadly, and privileging academics’ research priorities over those of policymakers. Little empirical data analysing the processes or impact of evidence use in policy is available to inform researchers or decision-makers. EBP research often assumes that policymakers do not use evidence and that more evidence – meaning research evidence – use would benefit policymakers and populations. We argue that these assumptions are unsupported, biasing much of EBP research. The agenda of ‘getting evidence into policy’ has side-lined the empirical description and analysis of how research and policy actually interact in vivo. Rather than asking how research evidence can be made more influential, academics should aim to understand what influences and constitutes policy, and produce more critically and theoretically informed studies of decision-making. We question the main assumptions made by EBP researchers, explore the implications of doing so, and propose new directions for EBP research, and health policy. PMID:25023520

  8. Evidence for epithelial-mesenchymal transitions in adult liver cells.

    PubMed

    Sicklick, Jason K; Choi, Steve S; Bustamante, Marcia; McCall, Shannon J; Pérez, Elizabeth Hernández; Huang, Jiawen; Li, Yin-Xiong; Rojkind, Marcos; Diehl, Anna Mae

    2006-10-01

    Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epithelial-mesenchymal transitions (EMT). During EMT, cells coexpress epithelial and mesenchymal cell markers. To determine whether EMT occurs in adult liver cells, we analyzed the expression profile of primary HSC, two HSC lines, and hepatic epithelial progenitors. As expected, all HSC expressed HSC markers. Surprisingly, these markers were also expressed by epithelial progenitors. In addition, one HSC line expressed typical epithelial progenitor mRNAs, and these epithelial markers were inducible in the second HSC line. In normal and damaged livers, small ductular-type cells stained positive for an HSC marker. In conclusion, HSC and hepatic epithelial progenitors both coexpress epithelial and mesenchymal markers, providing evidence that EMT occurs in adult liver cells.

  9. Direct and indirect evidence for earthquakes; an example from the Lake Tahoe Basin, California-Nevada

    NASA Astrophysics Data System (ADS)

    Maloney, J. M.; Noble, P. J.; Driscoll, N. W.; Kent, G.; Schmauder, G. C.

    2012-12-01

    High-resolution seismic CHIRP data can image direct evidence of earthquakes (i.e., offset strata) beneath lakes and the ocean. Nevertheless, direct evidence often is not imaged due to conditions such as gas in the sediments, or steep basement topography. In these cases, indirect evidence for earthquakes (i.e., debris flows) may provide insight into the paleoseismic record. The four sub-basins of the tectonically active Lake Tahoe Basin provide an ideal opportunity to image direct evidence for earthquake deformation and compare it to indirect earthquake proxies. We present results from high-resolution seismic CHIRP surveys in Emerald Bay, Fallen Leaf Lake, and Cascade Lake to constrain the recurrence interval on the West Tahoe Dollar Point Fault (WTDPF), which was previously identified as potentially the most hazardous fault in the Lake Tahoe Basin. Recently collected CHIRP profiles beneath Fallen Leaf Lake image slide deposits that appear synchronous with slides in other sub-basins. The temporal correlation of slides between multiple basins suggests triggering by events on the WTDPF. If correct, we postulate a recurrence interval for the WTDPF of ~3-4 k.y., indicating that the WTDPF is near its seismic recurrence cycle. In addition, CHIRP data beneath Cascade Lake image strands of the WTDPF that offset the lakefloor as much as ~7 m. The Cascade Lake data combined with onshore LiDAR allowed us to map the geometry of the WTDPF continuously across the southern Lake Tahoe Basin and yielded an improved geohazard assessment.

  10. Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass

    PubMed Central

    Guo, Ge; von Meyenn, Ferdinand; Santos, Fatima; Chen, Yaoyao; Reik, Wolf; Bertone, Paul; Smith, Austin; Nichols, Jennifer

    2016-01-01

    Summary Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals. PMID:26947977

  11. Lattice-free models of directed cell motility

    NASA Astrophysics Data System (ADS)

    Irons, Carolyn; Plank, Michael J.; Simpson, Matthew J.

    2016-01-01

    Directed cell migration often occurs when individual cells move in response to an external chemical stimulus. Cells can respond by moving in either the direction of increasing (chemoattraction) or decreasing (chemorepulsion) concentration. Many previous models of directed cell migration use a lattice-based framework where agents undergo a lattice-based random walk and the direction of nearest-neighbour motility events is biased in a preferred direction. Such lattice-based models can lead to unrealistic configurations of agents, since the agents always move on an artificial lattice structure which is never observed experimentally. We present a lattice-free model of directed cell migration that incorporates two key features. First, agents move on a continuous domain, with the possibility that there is some preferred direction of motion. Second, to be consistent with experimental observations, we enforce a crowding mechanism so that motility events that would lead to agent overlap are not permitted. We compare simulation data from the new lattice-free model with a more traditional lattice-based model. To provide additional insight into the lattice-free model, we construct an approximate conservation statement which corresponds to a nonlinear advection-diffusion equation in the continuum limit. The solution of this mean-field model compares well with averaged data from the individual-based model.

  12. Footprints reveal direct evidence of group behavior and locomotion in Homo erectus

    PubMed Central

    Hatala, Kevin G.; Roach, Neil T.; Ostrofsky, Kelly R.; Wunderlich, Roshna E.; Dingwall, Heather L.; Villmoare, Brian A.; Green, David J.; Harris, John W. K.; Braun, David R.; Richmond, Brian G.

    2016-01-01

    Bipedalism is a defining feature of the human lineage. Despite evidence that walking on two feet dates back 6–7 Ma, reconstructing hominin gait evolution is complicated by a sparse fossil record and challenges in inferring biomechanical patterns from isolated and fragmentary bones. Similarly, patterns of social behavior that distinguish modern humans from other living primates likely played significant roles in our evolution, but it is exceedingly difficult to understand the social behaviors of fossil hominins directly from fossil data. Footprints preserve direct records of gait biomechanics and behavior but they have been rare in the early human fossil record. Here we present analyses of an unprecedented discovery of 1.5-million-year-old footprint assemblages, produced by 20+ Homo erectus individuals. These footprints provide the oldest direct evidence for modern human-like weight transfer and confirm the presence of an energy-saving longitudinally arched foot in H. erectus. Further, print size analyses suggest that these H. erectus individuals lived and moved in cooperative multi-male groups, offering direct evidence consistent with human-like social behaviors in H. erectus. PMID:27403790

  13. Direct evidence of central European forest refugia during the last glacial period based on mollusc fossils

    NASA Astrophysics Data System (ADS)

    Juřičková, Lucie; Horáčková, Jitka; Ložek, Vojen

    2014-07-01

    Although there is evidence from molecular studies for the existence of central European last glacial refugia for temperate species, there is still a great lack of direct fossil records to confirm this theory. Here we bring such evidence in the form of fossil shells from twenty strictly forest land snail species, which were recorded in radiocarbon-dated late glacial or older mollusc assemblages of nine non-interrupted mollusc successions situated in the Western Carpathians, and one in the Bohemian Massif. We proposed that molluscs survived the last glacial period in central Europe in isolated small patches of broadleaf forest, which we unequivocally demonstrate for two sites of last glacial maximum age.

  14. Cognitive remediation therapy for mood disorders: rationale, early evidence, and future directions.

    PubMed

    Bowie, Christopher R; Gupta, Maya; Holshausen, Katherine

    2013-06-01

    People with mood disorders experience cognitive impairments that are predictive of functional disability. Cognitive remediation (CR) is an empirically validated intervention that is designed to remediate neurocognitive deficits and improve functioning. Although much of the focus of this treatment during the last decade has centred on attention deficit disorders, brain injury, and schizophrenia spectrum disorders, emerging evidence suggests that CR is an effective intervention for mood disorders and that these treatment effects translate into improvements in cognitive performance and possibly functioning. Our review aims to examine the profile and magnitude of cognitive impairments in mood disorders, review the evidence in support of CR for this population, and discuss future research directions in CR.

  15. Direct Evidence for Daily Plasticity of Electrical Coupling between Rod Photoreceptors in the Mammalian Retina

    PubMed Central

    Jin, Nan Ge

    2016-01-01

    Rod photoreceptors are electrically coupled through gap junctions. Coupling is a key determinant of their light response properties, but whether rod electrical coupling is dynamically regulated remains elusive and controversial. Here, we have obtained direct measurements of the conductance between adjacent rods in mouse retina and present evidence that rod electrical coupling strength is dependent on the time of day, the lighting conditions, and the mouse strain. Specifically, we show in CBA/Ca mice that under circadian conditions, the rod junctional conductance has a median value of 98 pS during the subjective day and of 493 pS during the subjective night. In C57BL/6 mice, the median junctional conductance between dark-adapted rods is ∼140 pS, regardless of the time in the circadian cycle. Adaptation to bright light decreases the rod junctional conductance to ∼0 pS, regardless of the time of day or the mouse strain. Together, these results establish the high degree of plasticity of rod electrical coupling over the course of the day. Estimates of the rod coupling strength will provide a foundation for further investigations of rod interactions and the role of rod coupling in the ability of the visual system to anticipate, assimilate, and respond to the daily changes in ambient light intensity. SIGNIFICANCE STATEMENT Many cells in the CNS communicate via gap junctions, or electrical synapses, the regulation of which remains largely unknown. Here, we show that the strength of electrical coupling between rod photoreceptors of the retina is regulated by the time of day and the lighting conditions. This mechanism may help us understand some key aspects of day and night vision as well as some visual malfunctions. PMID:26740659

  16. A direct 2-propanol polymer electrolyte fuel cell

    NASA Astrophysics Data System (ADS)

    Cao, Dianxue; Bergens, Steven H.

    We report the performance of a polymer electrolyte membrane direct 2-propanol fuel cell (DPFC). The cell consisted of a Pt-Ru (atomic ratio of 1:1) black anode, a Pt black cathode, and a Nafion ®-117 membrane electrolyte. The cell was operated at 90 °C with aqueous 2-propanol as fuel and with oxygen as oxidant. The performance of the cell operating on 2-propanol is substantially higher than when it was operating on methanol at current densities lower than ˜200 mA/cm 2. The electrical efficiency of the direct 2-propanol fuel cell is nearly 1.5 times that of the direct methanol fuel cell at power densities below 128 mW/cm 2. Studies on the effects of electrocatalyst loading, of 2-propanol concentration, and of oxygen pressure on cell performance indicate that the cells operating on 2-propanol require lower anode and cathode loadings than cells operating on methanol. Cathode poisoning by 2-propanol is less severe than by methanol. Hydrogen gas evolution observed at the anode at low current densities indicated that catalytic dehydrogenation of 2-propanol occurred over the anode catalyst. A rapid voltage drop occurred at high current densities and after operating the cell for extended periods of time at constant current. The rapid voltage drop is an anode phenomenon.

  17. On direct and indirect methanol fuel cells for transportation applications

    SciTech Connect

    Ren, Xiaoming; Wilson, M.S.; Gottesfeld, S.

    1995-09-01

    Power densities in electrolyte Direct Methanol Fuel Cells have been achieved which are only three times lower than those achieved with similar reformate/air fuel cells. Remaining issues are: improved anode catalyst activity, demonstrated long-term stable performance, and high fuel efficiencies.

  18. Parametric Design Studies on a Direct Liquid Feed Fuel Cell

    NASA Technical Reports Server (NTRS)

    Frank, H. A.; Narayanan, S. R.; Nakamura, B.; Surampudi, S.; Halpert, G.

    1995-01-01

    Parametric design studies were carried out on a direct methanol liquid feed fuel cell employing 1 M MeOH fuel, air and oxygen as oxidant in a 2 inch x 2 inch cell employing polymeric electrolyte membranes. Measurements include voltage-current output parameters, methanol crossover rate, and impedance as a function of several design and operational variables. Design variables are described.

  19. On direct and indirect methanol fuel cells for transportation applications

    SciTech Connect

    Gottesfield, S.

    1996-04-01

    Research on direct oxidation methanol fuel cells (DMFCs) and polymer electrolyte fuel cells (PEFCs) is discussed. Systems considered for transportation applications are addressed. The use of platinum/ruthenium anode electrocatalysts and platinum cathode electrocatalysts in polymer electrolyte DMFCs has resulted in significant performance enhancements.

  20. Paxillin-kinase-linker tyrosine phosphorylation regulates directional cell migration.

    PubMed

    Yu, Jianxin A; Deakin, Nicholas O; Turner, Christopher E

    2009-11-01

    Directed cell migration requires the coordination of growth factor and cell adhesion signaling and is of fundamental importance during embryonic development, wound repair, and pathological conditions such as tumor metastasis. Herein, we demonstrate that the ArfGAP, paxillin-kinase-linker (PKL/GIT2), is tyrosine phosphorylated in response to platelet-derived growth factor (PDGF) stimulation, in an adhesion dependent manner and is necessary for directed cell migration. Using a combination of pharmacological inhibitors, knockout cells and kinase mutants, FAK, and Src family kinases were shown to mediate PDGF-dependent PKL tyrosine phosphorylation. In fibroblasts, expression of a PKL mutant lacking the principal tyrosine phosphorylation sites resulted in loss of wound-induced cell polarization as well as directional migration. PKL phosphorylation was necessary for PDGF-stimulated PKL binding to the focal adhesion protein paxillin and expression of paxillin or PKL mutants defective in their respective binding motifs recapitulated the polarization defects. RNA interference or expression of phosphorylation mutants of PKL resulted in disregulation of PDGF-stimulated Rac1 and PAK activities, reduction of Cdc42 and Erk signaling, as well as mislocalization of betaPIX. Together these studies position PKL as an integral component of growth factor and cell adhesion cross-talk signaling, controlling the development of front-rear cell polarity and directional cell migration.

  1. Directed differentiation of pluripotent stem cells to kidney cells.

    PubMed

    Lam, Albert Q; Freedman, Benjamin S; Bonventre, Joseph V

    2014-07-01

    Regenerative medicine affords a promising therapeutic strategy for the treatment of patients with chronic kidney disease. Nephron progenitor cell populations exist only during embryonic kidney development. Understanding the mechanisms by which these populations arise and differentiate is integral to the challenge of generating new nephrons for therapeutic purposes. Pluripotent stem cells (PSCs), comprising embryonic stem cells, and induced pluripotent stem cells (iPSCs) derived from adults, have the potential to generate functional kidney cells and tissue. Studies in mouse and human PSCs have identified specific approaches to the addition of growth factors, including Wnt and fibroblast growth factor, that can induce PSC differentiation into cells with phenotypic characteristics of nephron progenitor populations with the capacity to form kidney-like structures. Although significant progress has been made, further studies are necessary to confirm the production of functional kidney cells and to promote their three-dimensional organization into bona fide kidney tissue. Human PSCs have been generated from patients with kidney diseases, including polycystic kidney disease, Alport syndrome, and Wilms tumor, and may be used to better understand phenotypic consequences of naturally occurring genetic mutations and to conduct "clinical trials in a dish". The capability to generate human kidney cells from PSCs has significant translational applications, including the bioengineering of functional kidney tissue, use in drug development to test compounds for efficacy and toxicity, and in vitro disease modeling.

  2. Direct Evidence for Vision-based Control of Flight Speed in Budgerigars.

    PubMed

    Schiffner, Ingo; Srinivasan, Mandyam V

    2015-06-05

    We have investigated whether, and, if so, how birds use vision to regulate the speed of their flight. Budgerigars, Melopsittacus undulatus, were filmed in 3-D using high-speed video cameras as they flew along a 25 m tunnel in which stationary or moving vertically oriented black and white stripes were projected on the side walls. We found that the birds increased their flight speed when the stripes were moved in the birds' flight direction, but decreased it only marginally when the stripes were moved in the opposite direction. The results provide the first direct evidence that Budgerigars use cues based on optic flow, to regulate their flight speed. However, unlike the situation in flying insects, it appears that the control of flight speed in Budgerigars is direction-specific. It does not rely solely on cues derived from optic flow, but may also be determined by energy constraints.

  3. Methanol crossover in direct methanol fuel cell systems.

    SciTech Connect

    Pivovar, B. S.; Bender, G.; Davey, J. R.; Zelenay, P.

    2003-01-01

    Direct methanol fuel cells (DMFCs) are currently being investigated for a number of different applications from several milliwatts to near kilowatt size scales (cell phones, laptops, auxiliary power units, etc .). Because methanol has a very high energy density, over 6000 W hr/kg, a DMFC can possibly have greatly extended lifetimes compared to the batteries, doesn't present the storage problems associated with hydrogen fuel cells and can possibly operate more efficiently and cleanly than internal combustion engines.

  4. Direct evidence for encoding of motion streaks in human visual cortex

    PubMed Central

    Apthorp, Deborah; Schwarzkopf, D. Samuel; Kaul, Christian; Bahrami, Bahador; Alais, David; Rees, Geraint

    2013-01-01

    Temporal integration in the visual system causes fast-moving objects to generate static, oriented traces (‘motion streaks’), which could be used to help judge direction of motion. While human psychophysics and single-unit studies in non-human primates are consistent with this hypothesis, direct neural evidence from the human cortex is still lacking. First, we provide psychophysical evidence that faster and slower motions are processed by distinct neural mechanisms: faster motion raised human perceptual thresholds for static orientations parallel to the direction of motion, whereas slower motion raised thresholds for orthogonal orientations. We then used functional magnetic resonance imaging to measure brain activity while human observers viewed either fast (‘streaky’) or slow random dot stimuli moving in different directions, or corresponding static-oriented stimuli. We found that local spatial patterns of brain activity in early retinotopic visual cortex reliably distinguished between static orientations. Critically, a multivariate pattern classifier trained on brain activity evoked by these static stimuli could then successfully distinguish the direction of fast (‘streaky’) but not slow motion. Thus, signals encoding static-oriented streak information are present in human early visual cortex when viewing fast motion. These experiments show that motion streaks are present in the human visual system for faster motion. PMID:23222445

  5. A Computer Model for Direct Carbonate Fuel Cells

    SciTech Connect

    Ding, J.; Patel, P.S.; Farooque, M.; Maru, H.C.

    1997-04-01

    A 3-D computer model, describing fluid flow, heat and mass transfer, and chemical and electrochemical reaction processes, has been developed for guiding the direct carbonate fuel cell (DFC) stack design. This model is able to analyze the direct internal reforming (DIR) as well as the integrated IIR (indirect internal reforming)-DIR designs. Reasonable agreements between computed and fuel cell tested results, such as flow variations, temperature distributions, cell potentials, and exhaust gas compositions as well as methane conversions, were obtained. Details of the model and comparisons of the modeling results with experimental DFC stack data are presented in the paper.

  6. Direct evidence for microbial-derived soil organic matter formation and its ecophysiological controls

    NASA Astrophysics Data System (ADS)

    Kallenbach, Cynthia M.; Frey, Serita D.; Grandy, A. Stuart

    2016-11-01

    Soil organic matter (SOM) and the carbon and nutrients therein drive fundamental submicron- to global-scale biogeochemical processes and influence carbon-climate feedbacks. Consensus is emerging that microbial materials are an important constituent of stable SOM, and new conceptual and quantitative SOM models are rapidly incorporating this view. However, direct evidence demonstrating that microbial residues account for the chemistry, stability and abundance of SOM is still lacking. Further, emerging models emphasize the stabilization of microbial-derived SOM by abiotic mechanisms, while the effects of microbial physiology on microbial residue production remain unclear. Here we provide the first direct evidence that soil microbes produce chemically diverse, stable SOM. We show that SOM accumulation is driven by distinct microbial communities more so than clay mineralogy, where microbial-derived SOM accumulation is greatest in soils with higher fungal abundances and more efficient microbial biomass production.

  7. Direct evidence for microbial-derived soil organic matter formation and its ecophysiological controls

    PubMed Central

    Kallenbach, Cynthia M.; Frey, Serita D.; Grandy, A. Stuart

    2016-01-01

    Soil organic matter (SOM) and the carbon and nutrients therein drive fundamental submicron- to global-scale biogeochemical processes and influence carbon-climate feedbacks. Consensus is emerging that microbial materials are an important constituent of stable SOM, and new conceptual and quantitative SOM models are rapidly incorporating this view. However, direct evidence demonstrating that microbial residues account for the chemistry, stability and abundance of SOM is still lacking. Further, emerging models emphasize the stabilization of microbial-derived SOM by abiotic mechanisms, while the effects of microbial physiology on microbial residue production remain unclear. Here we provide the first direct evidence that soil microbes produce chemically diverse, stable SOM. We show that SOM accumulation is driven by distinct microbial communities more so than clay mineralogy, where microbial-derived SOM accumulation is greatest in soils with higher fungal abundances and more efficient microbial biomass production. PMID:27892466

  8. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells

    PubMed Central

    Ottone, Cristina; Krusche, Benjamin; Whitby, Ariadne; Clements, Melanie; Quadrato, Giorgia; Pitulescu, Mara E.; Adams, Ralf H.; Parrinello, Simona

    2014-01-01

    The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialised endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculature-secreted soluble factors promote lineage progression of committed progenitors. Here we specifically investigated the role of cell-cell contact-dependent signalling in the vascular niche. Unexpectedly, we find that direct cell-cell interactions with endothelial cells enforces quiescence and promotes stem cell identity. Mechanistically, endothelial ephrinB2 and Jagged1 mediate these effects by suppressing cell-cycle entry downstream of mitogens and inducing stemness genes to jointly inhibit differentiation. In vivo, endothelial-specific ablation of either of the genes which encode these proteins, Efnb2 and Jag1 respectively, aberrantly activates quiescent stem cells, resulting in depletion. Thus, we identify the vasculature as a critical niche compartment for stem cell maintenance, furthering our understanding of how anchorage to the niche maintains stem cells within a pro-differentiative microenvironment. PMID:25283993

  9. Apoptosis by Direct Current Treatment in Tumor Cells and Tissues

    NASA Astrophysics Data System (ADS)

    Kim, Hongbae; Sim, Sungbo; Ahn, Saeyoung

    2003-10-01

    Electric field induces cell fusion, electroporation on biological cells, including apoptosis. Apoptosis is expressed in a series of natural enzymatic reactions for the natural elimination of unhealthy, genetically damaged, or otherwise aberrant cells that are not needed or not advantageous to the well-being of the organism. Its markers involve cell shrinkage, activation of intracellular caspase proteases, externalization of phosphatidylserine at the plasma membrane, and fragmentation of DNA. Direct electric fields using direct current have been exploited recently to investigate its effects on tumor cells and tissues, but the mechanism of direct electric fields has not been exhibited clearly other than by electroosmosis or pH changes. Direct electric field induces apoptosis in tumor cells cultured and tumor tissues as indicated by cell shrinkage, DNA fragmentation and tumor suppression. In our experiment that direct electric field was applied to tumor tissues via two needle electrodes inserted into tumor tissue 5mm at distance in parallel, pH changes resulted from electrochemical reaction, exhibiting about pH 9.0, 1.83, 2.0 in the vicinity of cathodic and anodic electrode, and at their mid-point, respectively. DNA fragmentation of tumor tissues destructed by direct electric field was analyzed by Tunel assay by ApopTag technology. As a result of this analysis, it showed that apoptosis in tumor tissue destructed was increased up to 59.1normal(control) tissues, showing 41.1, 31.1cathodic tissues. In vitro cell survival was exhibited that it was decreased with enhancing electric current intensity in the same condition of electrical charge 5C having different time applied. We will show results of apoptosis analyzed by flow cytometry in vitro.

  10. Extracellular matrix components direct porcine muscle stem cell behavior

    SciTech Connect

    Wilschut, Karlijn J.; Haagsman, Henk P.; Roelen, Bernard A.J.

    2010-02-01

    In muscle tissue, extracellular matrix proteins, together with the vasculature system, muscle-residence cells and muscle fibers, create the niche for muscle stem cells. The niche is important in controlling proliferation and directing differentiation of muscle stem cells to sustain muscle tissue. Mimicking the extracellular muscle environment improves tools exploring the behavior of primary muscle cells. Optimizing cell culture conditions to maintain muscle commitment is important in stem cell-based studies concerning toxicology screening, ex vivo skeletal muscle tissue engineering and in the enhancement of clinical efficiency. We used the muscle extracellular matrix proteins collagen type I, fibronectin, laminin, and also gelatin and Matrigel as surface coatings of tissue culture plastic to resemble the muscle extracellular matrix. Several important factors that determine myogenic commitment of the primary muscle cells were characterized by quantitative real-time RT-PCR and immunofluorescence. Adhesion of high PAX7 expressing satellite cells was improved if the cells were cultured on fibronectin or laminin coatings. Cells cultured on Matrigel and laminin coatings showed dominant integrin expression levels and exhibited an activated Wnt pathway. Under these conditions both stem cell proliferation and myogenic differentiation capacity were superior if compared to cells cultured on collagen type I, fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred coatings to sustain the proliferation and myogenic differentiation capacity of the primary porcine muscle stem cells, when cells are removed from their natural environment for in vitro culture.

  11. Paxillin controls directional cell motility in response to physical cues.

    PubMed

    Sero, Julia E; German, Alexandra E; Mammoto, Akiko; Ingber, Donald E

    2012-01-01

    Physical cues from the extracellular environment that influence cell shape and directional migration are transduced into changes in cytoskeletal organization and biochemistry through integrin-based cell adhesions to extracellular matrix (ECM). Paxillin is a focal adhesion (FA) scaffold protein that mediates integrin anchorage to the cytoskeleton, and has been implicated in regulation of FA assembly and cell migration. To determine whether paxillin is involved in coupling mechanical distortion with directional movement, cell shape was physically constrained by culturing cells on square-shaped fibronectin-coated adhesive islands surrounded by non-adhesive barrier regions that were created with a microcontact printing technique. Square-shaped cells preferentially formed FAs and extended lamellipodia from their corner regions when stimulated with PDGF, and loss of paxillin resulted in loss of this polarized response. Selective expression of the N- and C-terminal domains of paxillin produced opposite, but complementary, effects on suppressing or promoting lamellipodia formation in different regions of square cells, which corresponded to directional motility defects in vitro. Paxillin loss or mutation was also shown to affect the formation of circular dorsal ruffles, and this corresponded to changes in cell invasive behavior in 3D. This commentary addresses the implications of these findings in terms of how a multifunctional FA scaffold protein can link physical cues to cell adhesion, protrusion and membrane trafficking so as to control directional migration in 2D and 3D. We also discuss how microengineered ECM islands and in vivo model systems can be used to further elucidate the functions of paxillin in directional migration.

  12. HPV Direct Flow CHIP: a new human papillomavirus genotyping method based on direct PCR from crude-cell extracts.

    PubMed

    Herraez-Hernandez, Elsa; Alvarez-Perez, Martina; Navarro-Bustos, Gloria; Esquivias, Javier; Alonso, Sonia; Aneiros-Fernandez, Jose; Lacruz-Pelea, Cesar; Sanchez-Aguera, Magdalena; Santamaria, Javier Saenz; de Antonio, Jesus Chacon; Rodriguez-Peralto, Jose Luis

    2013-10-01

    HPV Direct Flow CHIP is a newly developed test for identifying 18 high-risk and 18 low-risk human papillomavirus (HPV) genotypes. It is based on direct PCR from crude-cell extracts, automatic flow-through hybridization, and colorimetric detection. The aim of this study was to evaluate the performance of HPV Direct Flow CHIP in the analysis of 947 samples from routine cervical screening or the follow-up of abnormal Pap smears. The specimens were dry swab samples, liquid-based cytology samples, or formalin-fixed paraffin-embedded tissues. The genotype distribution was in agreement with known epidemiological data for the Spanish population. Three different subgroups of the samples were also tested by Linear Array (LA) HPV Genotyping Test (n=108), CLART HPV2 (n=82), or Digene Hybrid Capture 2 (HC2) HPV DNA Test (n=101). HPV positivity was 73.6% by HPV Direct Flow CHIP versus 67% by LA, 65.9% by HPV Direct Flow CHIP versus 59.8% by CLART, and 62.4% by HPV Direct Flow CHIP versus 42.6% by HC2. HPV Direct Flow CHIP showed a positive agreement of 88.6% with LA (k=0.798), 87.3% with CLART (k=0.818), and 68.2% with HC2 (k=0.618). In conclusion, HPV Direct Flow CHIP results were comparable with those of the other methods tested. Although further investigation is needed to compare the performance of this new test with a gold-standard reference method, these preliminary findings evidence the potential value of HPV Direct Flow CHIP in HPV vaccinology and epidemiology studies.

  13. Evidence that cell surface heparan sulfate is involved in the high affinity thrombin binding to cultured porcine aortic endothelial cells.

    PubMed Central

    Shimada, K; Ozawa, T

    1985-01-01

    It has been postulated that thrombin binds to endothelial cells through, at least in part, cell surface glycosaminoglycans such as heparan sulfate, which could serve as antithrombin cofactor on the endothelium. In the present study, we have directly evaluated the binding of 125I-labeled bovine thrombin to cultured porcine aortic endothelial cells. The thrombin binding to the cell surface was rapid, reversible, and displaced by enzymatically inactive diisopropylphosphoryl-thrombin. The concentration of thrombin at half-maximal binding was approximately 20 nM. Both specific and nonspecific binding of 125I-thrombin to the endothelial cell surface was partially inhibited in the presence of protamine sulfate, after the removal of cell surface heparan sulfate by the treatment of cells with crude Flavobacterium heparinum enzyme or purified heparitinase. The binding as a function of the concentration of thrombin revealed that the maximal amount of specific binding was reduced by approximately 50% with little alteration in binding affinity by these enzymatic treatments. The reversibility and active-site independence as well as the rate of the binding did not change after heparitinase treatment. Whereas removal of chondroitin sulfates by chondroitin ABC lyase treatment of cells did not affect the binding, identical enzymatic treatments of [35S]sulfate-labeled cells showed that either heparan sulfate or chondroitin sulfate was selectively and completely removed from the cell surface by heparitinase or chondroitin ABC lyase treatment, respectively. Furthermore, proteolysis of cell surface proteins by the purified glycosaminoglycan lyases was excluded by the identical enzymatic treatments of [3H]leucine-labeled or cell surface radioiodinated cells. Our results provide the first direct evidence that heparan sulfate on the cell surface is involved in the high-affinity, active site-independent thrombin binding by endothelial cells, and also suggest the presence of thrombin

  14. High specific power, direct methanol fuel cell stack

    DOEpatents

    Ramsey, John C.; Wilson, Mahlon S.

    2007-05-08

    The present invention is a fuel cell stack including at least one direct methanol fuel cell. A cathode manifold is used to convey ambient air to each fuel cell, and an anode manifold is used to convey liquid methanol fuel to each fuel cell. Tie-bolt penetrations and tie-bolts are spaced evenly around the perimeter to hold the fuel cell stack together. Each fuel cell uses two graphite-based plates. One plate includes a cathode active area that is defined by serpentine channels connecting the inlet manifold with an integral flow restrictor to the outlet manifold. The other plate includes an anode active area defined by serpentine channels connecting the inlet and outlet of the anode manifold. Located between the two plates is the fuel cell active region.

  15. Direct-to-consumer marketing of evidence-based psychological interventions: introduction.

    PubMed

    Santucci, Lauren C; McHugh, R Kathryn; Barlow, David H

    2012-06-01

    The dissemination and implementation of evidence-based psychological interventions (EBPIs) to service provision settings has been a major challenge. Most efforts to disseminate and implement EBPIs have focused on clinicians and clinical systems as the consumers of these treatments and thus have targeted efforts to these groups. An alternative, complementary approach to achieve more widespread utilization of EBPIs is to disseminate directly to patients themselves. The aim of this special section is to explore several direct-to-consumer (i.e., patient) dissemination and education efforts currently underway. This manuscript highlights the rationale for direct-to-patient dissemination strategies as well as the application of marketing science to dissemination efforts. Achieving greater access to EBPIs will require the use of multiple approaches to overcome the many and varied barriers to successful dissemination and implementation.

  16. Direct evidence of strain transfer for InAs island growth on compliant Si substrates

    SciTech Connect

    Marçal, L. A. B.; Magalhães-Paniago, R.; Malachias, Angelo; Richard, M.-I.; Cavallo, F.; Lagally, M. G.; Schmidt, O. G.; Schülli, T. Ü.; Deneke, Ch.

    2015-04-13

    Semiconductor heteroepitaxy on top of thin compliant layers has been explored as a path to make inorganic electronics mechanically flexible as well as to integrate materials that cannot be grown directly on rigid substrates. Here, we show direct evidences of strain transfer for InAs islands on freestanding Si thin films (7 nm). Synchrotron X-ray diffraction measurements using a beam size of 300 × 700 nm{sup 2} can directly probe the strain status of the compliant substrate underneath deposited islands. Using a recently developed diffraction mapping technique, three-dimensional reciprocal space maps were reconstructed around the Si (004) peak for specific illuminated positions of the sample. The strain retrieved was analyzed using continuous elasticity theory via Finite-element simulations. The comparison of experiment and simulations yields the amount of strain from the InAs islands, which is transferred to the compliant Si thin film.

  17. Propagating Waves of Directionality and Coordination Orchestrate Collective Cell Migration

    PubMed Central

    Zaritsky, Assaf; Kaplan, Doron; Hecht, Inbal; Natan, Sari; Wolf, Lior; Gov, Nir S.; Ben-Jacob, Eshel; Tsarfaty, Ilan

    2014-01-01

    The ability of cells to coordinately migrate in groups is crucial to enable them to travel long distances during embryonic development, wound healing and tumorigenesis, but the fundamental mechanisms underlying intercellular coordination during collective cell migration remain elusive despite considerable research efforts. A novel analytical framework is introduced here to explicitly detect and quantify cell clusters that move coordinately in a monolayer. The analysis combines and associates vast amount of spatiotemporal data across multiple experiments into transparent quantitative measures to report the emergence of new modes of organized behavior during collective migration of tumor and epithelial cells in wound healing assays. First, we discovered the emergence of a wave of coordinated migration propagating backward from the wound front, which reflects formation of clusters of coordinately migrating cells that are generated further away from the wound edge and disintegrate close to the advancing front. This wave emerges in both normal and tumor cells, and is amplified by Met activation with hepatocyte growth factor/scatter factor. Second, Met activation was found to induce coinciding waves of cellular acceleration and stretching, which in turn trigger the emergence of a backward propagating wave of directional migration with about an hour phase lag. Assessments of the relations between the waves revealed that amplified coordinated migration is associated with the emergence of directional migration. Taken together, our data and simplified modeling-based assessments suggest that increased velocity leads to enhanced coordination: higher motility arises due to acceleration and stretching that seems to increase directionality by temporarily diminishing the velocity components orthogonal to the direction defined by the monolayer geometry. Spatial and temporal accumulation of directionality thus defines coordination. The findings offer new insight and suggest a basic

  18. Direct reprogramming of adult cells: avoiding the pluripotent state.

    PubMed

    Kelaini, Sophia; Cochrane, Amy; Margariti, Andriana

    2014-01-01

    The procedure of using mature, fully differentiated cells and inducing them toward other cell types while bypassing an intermediate pluripotent state is termed direct reprogramming. Avoiding the pluripotent stage during cellular conversions can be achieved either through ectopic expression of lineage-specific factors (transdifferentiation) or a direct reprogramming process that involves partial reprogramming toward the pluripotent stage. Latest advances in the field seek to alleviate concerns that include teratoma formation or retroviral usage when it comes to delivering reprogramming factors to cells. They also seek to improve efficacy and efficiency of cellular conversion, both in vitro and in vivo. The final products of this reprogramming approach could be then directly implemented in regenerative and personalized medicine.

  19. Chondrocytes Directly Transform into Bone Cells in Mandibular Condyle Growth

    PubMed Central

    Jing, Y.; Zhou, X.; Han, X.; Jing, J.; von der Mark, K.; Wang, J.; de Crombrugghe, B.; Hinton, R.J.; Feng, J.Q.

    2015-01-01

    For decades, it has been widely accepted that hypertrophic chondrocytes undergo apoptosis prior to endochondral bone formation. However, very recent studies in long bone suggest that chondrocytes can directly transform into bone cells. Our initial in vivo characterization of condylar hypertrophic chondrocytes revealed modest numbers of apoptotic cells but high levels of antiapoptotic Bcl-2 expression, some dividing cells, and clear alkaline phosphatase activity (early bone marker). Ex vivo culture of newborn condylar cartilage on a chick chorioallantoic membrane showed that after 5 d the cells on the periphery of the explants had begun to express Col1 (bone marker). The cartilage-specific cell lineage–tracing approach in triple mice containing Rosa 26tdTomato (tracing marker), 2.3 Col1GFP (bone cell marker), and aggrecan CreERT2 (onetime tamoxifen induced) or Col10-Cre (activated from E14.5 throughout adult stage) demonstrated the direct transformation of chondrocytes into bone cells in vivo. This transformation was initiated at the inferior portion of the condylar cartilage, in contrast to the initial ossification site in long bone, which is in the center. Quantitative data from the Col10-Cre compound mice showed that hypertrophic chondrocytes contributed to ~80% of bone cells in subchondral bone, ~70% in a somewhat more inferior region, and ~40% in the most inferior part of the condylar neck (n = 4, P < 0.01 for differences among regions). This multipronged approach clearly demonstrates that a majority of chondrocytes in the fibrocartilaginous condylar cartilage, similar to hyaline cartilage in long bones, directly transform into bone cells during endochondral bone formation. Moreover, ossification is initiated from the inferior portion of mandibular condylar cartilage with expansion in one direction. PMID:26341973

  20. Economics of Direct Hydrogen Polymer Electrolyte Membrane Fuel Cell Systems

    SciTech Connect

    Mahadevan, Kathyayani

    2011-10-04

    Battelle's Economic Analysis of PEM Fuel Cell Systems project was initiated in 2003 to evaluate the technology and markets that are near-term and potentially could support the transition to fuel cells in automotive markets. The objective of Battelle?s project was to assist the DOE in developing fuel cell systems for pre-automotive applications by analyzing the technical, economic, and market drivers of direct hydrogen PEM fuel cell adoption. The project was executed over a 6-year period (2003 to 2010) and a variety of analyses were completed in that period. The analyses presented in the final report include: Commercialization scenarios for stationary generation through 2015 (2004); Stakeholder feedback on technology status and performance status of fuel cell systems (2004); Development of manufacturing costs of stationary PEM fuel cell systems for backup power markets (2004); Identification of near-term and mid-term markets for PEM fuel cells (2006); Development of the value proposition and market opportunity of PEM fuel cells in near-term markets by assessing the lifecycle cost of PEM fuel cells as compared to conventional alternatives used in the marketplace and modeling market penetration (2006); Development of the value proposition of PEM fuel cells in government markets (2007); Development of the value proposition and opportunity for large fuel cell system application at data centers and wastewater treatment plants (2008); Update of the manufacturing costs of PEM fuel cells for backup power applications (2009).

  1. Direct evidence for a β1-adrenergic receptor–directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy

    PubMed Central

    Jahns, Roland; Boivin, Valérie; Hein, Lutz; Triebel, Sven; Angermann, Christiane E.; Ertl, Georg; Lohse, Martin J.

    2004-01-01

    Today, dilated cardiomyopathy (DCM) represents the main cause of severe heart failure and disability in younger adults and thus is a challenge for public health. About 30% of DCM cases are genetic in origin; however, the large majority of cases are sporadic, and a viral or immune pathogenesis is suspected. Following the established postulates for pathogenesis of autoimmune diseases, here we provide direct evidence that an autoimmune attack directed against the cardiac β1-adrenergic receptor may play a causal role in DCM. First, we immunized inbred rats against the second extracellular β1-receptor loop (β1-ECII; 100% sequence identity between human and rat) every month. All these rats developed first, receptor-stimulating anti–β1-ECII Ab’s and then, after 9 months, progressive severe left ventricular dilatation and dysfunction. Second, we transferred sera from anti–β1-ECII–positive and Ab-negative animals every month to healthy rats of the same strain. Strikingly, all anti–β1-ECII–transferred rats also developed a similar cardiomyopathic phenotype within a similar time frame, underlining the pathogenic potential of these receptor Ab’s. As a consequence, β1-adrenergic receptor–targeted autoimmune DCM should now be categorized with other known receptor Ab-mediated autoimmune diseases, such as Graves disease or myasthenia gravis. Although carried out in an experimental animal model, our findings should further encourage the development of therapeutic strategies that combat harmful anti–β1-ECII in receptor Ab–positive DCM patients. PMID:15146239

  2. Analysis of primary cilia in directional cell migration in fibroblasts.

    PubMed

    Christensen, Søren T; Veland, Iben R; Schwab, Albrecht; Cammer, Michael; Satir, Peter

    2013-01-01

    Early studies of migrating fibroblasts showed that primary cilia orient in front of the nucleus and point toward the leading edge. Recent work has shown that primary cilia coordinate a series of signaling pathways critical to fibroblast cell migration during development and in wound healing. In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration but also more generally in delineating response pathways in cells with primary cilia.

  3. Alkaline direct alcohol fuel cells using an anion exchange membrane

    NASA Astrophysics Data System (ADS)

    Matsuoka, Koji; Iriyama, Yasutoshi; Abe, Takeshi; Matsuoka, Masao; Ogumi, Zempachi

    Alkaline direct alcohol fuel cells using an OH-form anion exchange membrane and polyhydric alcohols were studied. A high open circuit voltage of ca. 800 mV was obtained for a cell using Pt-Ru/C (anode) and Pt/C (cathode) at 323 K, which was about 100-200 mV higher than that for a DMFC using Nafion ®. The maximum power densities were in the order of ethylene glycol > glycerol > methanol > erythritol > xylitol. Silver catalysts were used as a cathode catalyst to fabricate alkaline fuel cells, since silver catalyst is almost inactive in the oxidation of polyhydric alcohols. Alkaline direct ethylene glycol fuel cells using silver as a cathode catalyst gave excellent performance because higher concentrations of fuel could be supplied to the anode.

  4. Conceptual and methodological advances in cell-free directed evolution

    PubMed Central

    Dodevski, Igor; Markou, George C.; Sarkar, Casim A.

    2015-01-01

    Although cell-free directed evolution methods have been used to engineer proteins for nearly two decades, selections on more complex phenotypes have largely remained in the domain of cell-based engineering approaches. Here, we review recent conceptual advances that now enable in vitro display of multimeric proteins, integral membrane proteins, and proteins with an expanded amino acid repertoire. Additionally, we discuss methodological improvements that have enhanced the accessibility, efficiency, and robustness of cell-free approaches. Coupling these advances with the in vitro advantages of creating exceptionally large libraries and precisely controlling all experimental conditions, cell-free directed evolution is poised to contribute significantly to our understanding and engineering of more complex protein phenotypes. PMID:26093059

  5. Human embryonic stem cell derivation and directed differentiation.

    PubMed

    Trounson, A

    2005-01-01

    Human embryonic stem cells (hESCs) are produced from normal, chromosomally aneuploid and mutant human embryos, which are available from in vitro fertilisation (IVF) for infertility or preimplantation diagnosis. These hESC lines are an important resource for functional genomics, drug screening and eventually cell and gene therapy. The methods for deriving hESCs are well established and repeatable, and are relatively successful, with a ratio of 1:10 to 1:2 hESC lines established to embryos used. hESCs can be formed from morula and blastocyst-stage embryos and from isolated inner cell mass cell (ICM) clusters. The hESCs can be formed and maintained on mouse or human somatic cells in serum-free conditions, and for several passages in cell-free cultures. The hESCs can be transfected with DNA constructs. Their gene expression profiles are being described and immunological characteristics determined. They may be grown indefinitely in culture while maintaining their original karyotype but this must be confirmed from time to time. hESCs spontaneously differentiate in the absence of the appropriate cell feeder layer, when overgrown in culture and when isolated from the ESC colony. All three major embryonic lineages are produced in differentiating attachment cultures and in unattached embryoid bodies. Cell progenitors of interest can be identified by markers, expression of reporter genes and characteristic morphology, and the culture thereafter enriched for further culture to more mature cell types. The most advanced directed differentiation pathways have been developed for neural cells and cardiac muscle cells, but many other cell types including haematopoietic progenitors, endothelial cells, lung alveoli, keratinocytes, pigmented retinal epithelium, neural crest cells and motor neurones, hepatic progenitors and cells that have some markers of gut tissue and pancreatic cells have been produced. The prospects for regenerative medicine are significant and there is much

  6. Dynamic simulation of a direct carbonate fuel cell power plant

    SciTech Connect

    Ernest, J.B.; Ghezel-Ayagh, H.; Kush, A.K.

    1996-12-31

    Fuel Cell Engineering Corporation (FCE) is commercializing a 2.85 MW Direct carbonate Fuel Cell (DFC) power plant. The commercialization sequence has already progressed through construction and operation of the first commercial-scale DFC power plant on a U.S. electric utility, the 2 MW Santa Clara Demonstration Project (SCDP), and the completion of the early phases of a Commercial Plant design. A 400 kW fuel cell stack Test Facility is being built at Energy Research Corporation (ERC), FCE`s parent company, which will be capable of testing commercial-sized fuel cell stacks in an integrated plant configuration. Fluor Daniel, Inc. provided engineering, procurement, and construction services for SCDP and has jointly developed the Commercial Plant design with FCE, focusing on the balance-of-plant (BOP) equipment outside of the fuel cell modules. This paper provides a brief orientation to the dynamic simulation of a fuel cell power plant and the benefits offered.

  7. Enhanced methanol utilization in direct methanol fuel cell

    DOEpatents

    Ren, Xiaoming; Gottesfeld, Shimshon

    2001-10-02

    The fuel utilization of a direct methanol fuel cell is enhanced for improved cell efficiency. Distribution plates at the anode and cathode of the fuel cell are configured to distribute reactants vertically and laterally uniformly over a catalyzed membrane surface of the fuel cell. A conductive sheet between the anode distribution plate and the anodic membrane surface forms a mass transport barrier to the methanol fuel that is large relative to a mass transport barrier for a gaseous hydrogen fuel cell. In a preferred embodiment, the distribution plate is a perforated corrugated sheet. The mass transport barrier may be conveniently increased by increasing the thickness of an anode conductive sheet adjacent the membrane surface of the fuel cell.

  8. Direct Effect of Zinc on Mitochondrial Apoptogenesis in Prostate Cells

    PubMed Central

    Feng, Pei; Li, Tie-Luo; Guan, Zhi-Xin; Franklin, Renty B.; Costello, Leslie C.

    2015-01-01

    BACKGROUND Prostate epithelial cells uniquely accumulate significantly higher levels of zinc than other mammalian cells. We previously showed that the accumulation of high intracellular zinc levels in specific prostate cells results in the induction of apoptosis and the inhibition of cell growth. The apoptotic effect is due to zinc induction of mitochondrial apoptogenesis. We now report additional studies that corroborate this effect of zinc and provide insight into the mechanism of this unique effect. METHODS The effect of exposure to physiological levels of zinc on apoptosis was determined for three human prostate cell lines (PC-3, BPH, and HPR-1). Zinc-induced apoptosis was identified by DNA fragmentation. The direct effect of zinc on isolated mitochondrial preparations from each cell line was determined. The mitochondrial release of cytochrome c was determined by Western blot. RESULTS Exposure to zinc induced apoptosis in PC-3 and BPH cells but not in HPR-1 cells. The zinc accumulation in PC-3 (4.3 ± 0.3) and BPH (2.8 ± 0.4) was higher than that in HPR-1 cells (1.8 ± 0.1). The apoptotic effect of zinc on PC-3 cells could be observed as early as 4–6 hr of zinc treatment, and this effect was not reversible. The exposure of isolated mitochondria from PC-3 and BPH cells to zinc resulted in the release of cytochrome c; but zinc had no effect on mitochondria from HPR-1 cells. CONCLUSIONS Exposure to zinc induces apoptosis in PC-3 and BPH cells, which accumulate high intracellular levels of zinc, but not in HPR-1 cells, which do not accumulate high levels of zinc. Once initiated, the induction of apoptosis is not reversed by the removal of zinc, i.e., it is an irreversible process. The apoptogenic effect is due to a direct effect of zinc on mitochondria that results in the release of cytochrome c. The cell specificity of zinc induction of apoptogenesis is dependent on the ability of the cells to accumulate high levels of intracellular zinc and on the ability of

  9. Materials and Manufacturing Challenges of Direct Methanol Fuel Cells

    DTIC Science & Technology

    2009-04-27

    SPSf. Figure 5 shows four basic polymers in which benzimidazole (BIm), amino- benzimidazole (ABIm), nitrobenzimidazole (NBIm), and perimidine (PImd...Membranes Based on Sulfonated Polyetheretherketone and Polysulfone Bearing Benzimidazole Side Groups for Fuel Cells,” Electrochemistry Communications...Bearing Benzimidazole Side Groups for Direct Methanol Fuel Cells,” Electrochemical and Solid State Letters, Vol. 10, 2007, p. B70-B73. [12] Fu, Y.-Z

  10. Microtopography and flow modulate the direction of endothelial cell migration.

    PubMed

    Uttayarat, P; Chen, M; Li, M; Allen, F D; Composto, R J; Lelkes, P I

    2008-02-01

    The migration of vascular endothelial cells under flow can be modulated by the addition of chemical or mechanical stimuli. The aim of this study was to investigate how topographic cues derived from a substrate containing three-dimensional microtopography interact with fluid shear stress in directing endothelial cell migration. Subconfluent bovine aortic endothelial cells were seeded on fibronectin-coated poly(dimethylsiloxane) substrates patterned with a combinatorial array of parallel and orthogonal microgrooves ranging from 2 to 5 microm in width at a constant depth of 1 microm. During a 4-h time-lapse observation in the absence of flow, the majority of the prealigned cells migrated parallel to the grooves with the distribution of their focal adhesions (FAs) depending on the groove width. No change in this migratory pattern was observed after the cells were exposed to moderate shear stress (13.5 dyn/cm(2)), irrespective of groove direction with respect to flow. After 4-h exposure to high shear stress (58 dyn/cm(2)) parallel to the grooves, the cells continued to migrate in the direction of both grooves and flow. By contrast, when microgrooves were oriented perpendicular to flow, most cells migrated orthogonal to the grooves and downstream with flow. Despite the change in the migration direction of the cells under high shear stress, most FAs and actin microfilaments maintained their original alignment parallel to the grooves, suggesting that topographic cues were more effective than those derived from shear stress in guiding the orientation of cytoskeletal and adhesion proteins during the initial exposure to flow.

  11. Single cells for forensic DNA analysis--from evidence material to test tube.

    PubMed

    Brück, Simon; Evers, Heidrun; Heidorn, Frank; Müller, Ute; Kilper, Roland; Verhoff, Marcel A

    2011-01-01

    The purpose of this project was to develop a method that, while providing morphological quality control, allows single cells to be obtained from the surfaces of various evidence materials and be made available for DNA analysis in cases where only small amounts of cell material are present or where only mixed traces are found. With the SteREO Lumar.V12 stereomicroscope and UV unit from Zeiss, it was possible to detect and assess single epithelial cells on the surfaces of various objects (e.g., glass, plastic, metal). A digitally operated micromanipulator developed by aura optik was used to lift a single cell from the surface of evidence material and to transfer it to a conventional PCR tube or to an AmpliGrid(®) from Advalytix. The actual lifting of the cells was performed with microglobes that acted as carriers. The microglobes were held with microtweezers and were transferred to the DNA analysis receptacles along with the adhering cells. In a next step, the PCR can be carried out in this receptacle without removing the microglobe. Our method allows a single cell to be isolated directly from evidence material and be made available for forensic DNA analysis.

  12. Body image disturbance in children and adolescents with eating disorders. Current evidence and future directions.

    PubMed

    Legenbauer, Tanja; Thiemann, Pia; Vocks, Silja

    2014-01-01

    Body image is multifaceted and incorporates perceptual, affective, and cognitive components as well as behavioral features. Only few studies have examined the character of body-image disturbance in children/adolescents with eating disorders. It is unknown whether body-image disturbances in children/adolescent with eating disturbances are comparable to those of adult patients with eating disorders. Body-image disturbance might differ quantitatively and qualitatively according to the cognitive developmental status and the age of the individual. This paper provides an overview of the current evidence for body-image disturbance in children/adolescents with eating disorders, and how they compare with those adults with eating disorders. Current evidence indicates that older adolescent patients show similar deficits as adult patients with eating disorders, in particular for the attitudinal body-image component. However, evidence for a perceptual body-image disturbance in adolescent patients, in particular anorexia nervosa, is not conclusive. Reliable statements for childhood can hardly be made because clinical studies are not available. Investigations of body-image disturbance in children have focused on the predictive value for eating disorders. Limitations of the current evidence are discussed, and future directions for research and therapy are indicated.

  13. An evidence summary of the management of patients taking direct oral anticoagulants (DOACs) undergoing dental surgery.

    PubMed

    Johnston, S

    2016-05-01

    Direct oral anticoagulant (DOAC) drugs (dabigatran, rivaroxaban, and apixaban) have emerged in the last decade to overcome some of the drawbacks of existing medications. To date, little is known about the dental management of patients taking these drugs. This study was undertaken to establish the evidence for the management of patients undergoing dental procedures while taking these medications. A rapid review approach was used to identify clinical and scientific research related to dental surgery performed in patients taking DOACs in order to produce an evidence summary. The rapid review did not identify any systematic reviews or original clinical trials and the overall quality of evidence found was poor. Most of the literature consisted of non-structured review articles and guidance documents based on assumptions from non-dental data and expert opinion, and recommendations on best practice varied throughout. The findings from the review of the literature varied considerably. Currently, recommendations are based on poor quality scientific data and clinical trials are required to establish best evidence-based practice guidance.

  14. The planar cell polarity pathway directs parietal endoderm migration.

    PubMed

    LaMonica, Kristi; Bass, Maya; Grabel, Laura

    2009-06-01

    Parietal endoderm (PE) contributes to the yolk sac and is the first migratory cell type in the mammalian embryo. We can visualize PE migration in vitro using the F9 teratocarcinoma derived embryoid body outgrowth system and, show here that PE migration is directed by the non-canonical Wnt planar cell polarity (PCP) pathway via Rho/ROCK. Based on golgi apparatus localization and microtubule orientation, 68.6% of cells in control outgrowths are oriented in the direction of migration. Perturbation of Wnt signaling via sFRP treatment results in a loss of orientation coupled with an increase in cell migration. Inhibition of the PCP pathway at the level of Daam1 also results in a loss of cell orientation along with an increase in cell migration, as seen with sFRP treatment. Constitutively active Daam can inhibit the loss of orientation that occurs with sFRP treatment. We previously demonstrated that ROCK inhibition leads to an increase in cell migration, and we now show that these cells also lack oriented migration. Canonical Wnt signaling or the Rac arm of the PCP pathway does not appear to play a role in PE oriented migration. These data suggest the PCP pathway via Rho/ROCK modulates migration of PE.

  15. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces

    NASA Technical Reports Server (NTRS)

    Parker, Kevin Kit; Brock, Amy Lepre; Brangwynne, Cliff; Mannix, Robert J.; Wang, Ning; Ostuni, Emanuele; Geisse, Nicholas A.; Adams, Josephine C.; Whitesides, George M.; Ingber, Donald E.

    2002-01-01

    Directed cell migration is critical for tissue morphogenesis and wound healing, but the mechanism of directional control is poorly understood. Here we show that the direction in which cells extend their leading edge can be controlled by constraining cell shape using micrometer-sized extracellular matrix (ECM) islands. When cultured on square ECM islands in the presence of motility factors, cells preferentially extended lamellipodia, filopodia, and microspikes from their corners. Square cells reoriented their stress fibers and focal adhesions so that tractional forces were concentrated in these corner regions. When cell tension was dissipated, lamellipodia extension ceased. Mechanical interactions between cells and ECM that modulate cytoskeletal tension may therefore play a key role in the control of directional cell motility.

  16. The first direct evidence of a Late Devonian coelacanth fish feeding on conodont animals

    NASA Astrophysics Data System (ADS)

    Zatoń, Michał; Broda, Krzysztof; Qvarnström, Martin; Niedźwiedzki, Grzegorz; Ahlberg, Per Erik

    2017-04-01

    We describe the first known occurrence of a Devonian coelacanth specimen from the lower Famennian of the Holy Cross Mountains, Poland, with a conodont element preserved in its digestive tract. A small spiral and phosphatic coprolite (fossil excrement) containing numerous conodont elements and other unrecognized remains was also found in the same deposits. The coprolite is tentatively attributed to the coelacanth. Although it is unclear whether the Late Devonian coelacanth from Poland was an active predator or a scavenger, these finds provide the first direct evidence of feeding on conodont animals by early coelacanth fish, and one of the few evidences of feeding on these animals known to date. It also expands our knowledge about the diet and trophic relations between the Paleozoic marine animals in general.

  17. The first direct evidence of a Late Devonian coelacanth fish feeding on conodont animals.

    PubMed

    Zatoń, Michał; Broda, Krzysztof; Qvarnström, Martin; Niedźwiedzki, Grzegorz; Ahlberg, Per Erik

    2017-04-01

    We describe the first known occurrence of a Devonian coelacanth specimen from the lower Famennian of the Holy Cross Mountains, Poland, with a conodont element preserved in its digestive tract. A small spiral and phosphatic coprolite (fossil excrement) containing numerous conodont elements and other unrecognized remains was also found in the same deposits. The coprolite is tentatively attributed to the coelacanth. Although it is unclear whether the Late Devonian coelacanth from Poland was an active predator or a scavenger, these finds provide the first direct evidence of feeding on conodont animals by early coelacanth fish, and one of the few evidences of feeding on these animals known to date. It also expands our knowledge about the diet and trophic relations between the Paleozoic marine animals in general.

  18. Direct observation in medical education: a review of the literature and evidence for validity.

    PubMed

    Fromme, H Barrett; Karani, Reena; Downing, Steven M

    2009-08-01

    In 2000, the Accreditation Council for Medical Education introduced a new initiative that substantively changed the method by which residency programs are evaluated. In this new competency-based approach to residency education, assessment of performance became a main area of interest, and direct observation was offered as a tool to assess knowledge and skills. Despite being an inherent part of medical education as faculty and learners work together in clinical experiences, direct observation has traditionally been an informal and underused assessment method across all specialties. Residents and students report rarely being observed during their educational process, even though they value the experience. Reasons for this include a lack of faculty time, a lack of faculty skills, a potential stressful effect on the learner, and a perceived lack of validation of the assessment. This article examines the literature regarding the use of direct observation in medical education with a focus on validity evidence. We performed a PubMed search of articles pertaining to direct observation, using key words such as direct observation, performance observation, clinical observation, students, and residents. A subsequent search was conducted in known articles, focusing on variations of the term observation in the titles of articles and introducing the concept of clinical competence. In conclusion, direct observation is a unique and useful tool in the assessment of medical students and residents. Assessing learners in natural settings offers the opportunity to see beyond what they know and into what they actually do, which is fundamentally essential to training qualified physicians. Although the literature identifies several threats to its validity as an assessment, it also demonstrates methods to minimize those threats. Based on the current recommendations and need for performance assessment in education and with attention paid to the development and design, direct observation can

  19. Studies of Schwann cell proliferation. III. Evidence for the surface localization of the neurite mitogen

    PubMed Central

    1980-01-01

    In the preceding paper (Salzer et al., 1980, J. Cell Biol. 84:753-- 766), evidence was presented that a neurite membrane fraction could be used to stimulate Schwann cell proliferation in culture. In this study, we present evidence that the mitogenic signal by which intact neurites or neurite membranes stimulate Schwann cell proliferation is located at the neurite surface. This conclusion is based on the following observations: (a) stimulation of Schwann cell proliferation by neurons requires direct contact between neurites and Schwann cells, separation of the two cells by a permeable collagen diaphragm 6 microns thick prevents Schwann cell proliferation; (b) treatment of intact neurites with trypsin before preparation of neurite membranes abolishes the ability of these membranes to be mitogenic for Schwann cells; and (c) the mitogenic activity of neurite homogenates is exclusively localized in the particulate rather than the soluble fraction of the homogenate. The mitogenic component on the neurite surface is heat labile, and is inactivated by aldehyde fixation. Preliminary data suggest that the mitogenic effect of neurite on Schwann cells is not mediated by 3',5'- cyclic AMP. PMID:6153659

  20. Bifunctional activation of a direct methanol fuel cell

    NASA Astrophysics Data System (ADS)

    Kulikovsky, A. A.; Schmitz, H.; Wippermann, K.; Mergel, J.; Fricke, B.; Sanders, T.; Sauer, D. U.

    We report a novel method for performance recovery of direct methanol fuel cells. Lowering of air flow rate below a critical value turns the cell into bifunctional regime, when the oxygen-rich part of the cell generates current while the rest part works in electrolysis mode (electrolytic domain). Upon restoring the normal (super-critical) air flow rate, the galvanic performance of the electrolytic domain increases. This recovery effect is presumably attributed to Pt surface cleaning on the cathode with the simultaneous increase in catalyst utilization on the anode.

  1. Direct patterning of mammalian cells in an ultrasonic heptagon stencil.

    PubMed

    Bernassau, A L; Gesellchen, F; Macpherson, P G A; Riehle, M; Cumming, D R S

    2012-06-01

    We describe the construction of a ultrasonic device suitable for micro patterning particles and cells for tissue engineering applications. The device is formed by seven transducers shaped into a heptagon cavity. By exciting two and three transducers simultaneously, lines or hexagonal shapes can be formed with beads and cells. Furthermore, phase control of the transducers allows shifting the standing waves and thus patterning at different positions on a surface in a controlled manner. The paper discusses direct patterning of mammalian cells by ultrasound "stencil".

  2. Evidence for breathing modes in direct current, pulsed, and high power impulse magnetron sputtering plasmas

    SciTech Connect

    Yang, Yuchen; Zhou, Xue; Liu, Jason X.; Anders, André

    2016-01-18

    We present evidence for breathing modes in magnetron sputtering plasmas: periodic axial variations of plasma parameters with characteristic frequencies between 10 and 100 kHz. A set of azimuthally distributed probes shows synchronous oscillations of the floating potential. They appear most clearly when considering the intermediate current regime in which the direction of azimuthal spoke motion changes. Breathing oscillations were found to be superimposed on azimuthal spoke motion. Depending on pressure and current, one can also find a regime of chaotic fluctuations and one of stable discharges, the latter at high current. A pressure-current phase diagram for the different situations is proposed.

  3. Direct replication of Gervais & Norenzayan (2012): No evidence that analytic thinking decreases religious belief

    PubMed Central

    Sanchez, Clinton; Sundermeier, Brian; Gray, Kenneth

    2017-01-01

    Gervais & Norenzayan (2012) reported in Science a series of 4 experiments in which manipulations intended to foster analytic thinking decreased religious belief. We conducted a precise, large, multi-site pre-registered replication of one of these experiments. We observed little to no effect of the experimental manipulation on religious belief (d = 0.07 in the wrong direction, 95% CI[-0.12, 0.25], N = 941). The original finding does not seem to provide reliable or valid evidence that analytic thinking causes a decrease in religious belief. PMID:28234942

  4. Direct replication of Gervais & Norenzayan (2012): No evidence that analytic thinking decreases religious belief.

    PubMed

    Sanchez, Clinton; Sundermeier, Brian; Gray, Kenneth; Calin-Jageman, Robert J

    2017-01-01

    Gervais & Norenzayan (2012) reported in Science a series of 4 experiments in which manipulations intended to foster analytic thinking decreased religious belief. We conducted a precise, large, multi-site pre-registered replication of one of these experiments. We observed little to no effect of the experimental manipulation on religious belief (d = 0.07 in the wrong direction, 95% CI[-0.12, 0.25], N = 941). The original finding does not seem to provide reliable or valid evidence that analytic thinking causes a decrease in religious belief.

  5. The production and directed differentiation of human embryonic stem cells.

    PubMed

    Trounson, Alan

    2006-04-01

    Human embryonic stem cells (hESCs) are being rapidly produced from chromosomally euploid, aneuploid, and mutant human embryos that are available from in vitro fertilization clinics treating patients for infertility or preimplantation genetic diagnosis. These hESC lines are an important resource for functional genomics, drug screening, and, perhaps eventually, cell and gene therapy. The methods for deriving hESCs are well established and repeatable and are relatively successful with a ratio of 1:10 to 1:2 new hESC lines produced from 4- to 8-d-old morula and blastocysts and from isolated inner cell mass cell clusters of human blastocysts. The hESCs can be formed and maintained on human somatic cells in humanized serum-free culture conditions and for several passages in cell-free culture systems. The hESCs can be transfected with DNA constructs. Their gene expression profiles are being described and immunological characteristics determined. They may be grown indefinitely in vitro while maintaining their original karyotype and epigenetic status, but this needs to be confirmed from time to time in long-term cultures. hESCs spontaneously differentiate in the absence of the appropriate cell feeder layer, when overgrown in culture and when isolated from the ESC colony. All three major embryonic lineages are produced in differentiating flat attachment cultures and unattached embryoid bodies. Cell progenitors of interest can be identified by markers, expression of reporter genes, and characteristic morphology, and the cells thereafter enriched for progenitor types and further culture to more mature cell types. Directed differentiation systems are well developed for ectodermal pathways that result in neural and glial cells and the mesendodermal pathway for cardiac muscle cells and many other cell types including hematopoietic progenitors and endothelial cells. Directed differentiation into endoderm has been more difficult to achieve, perhaps because of the lack of markers of

  6. Cytochemical and cytofluorometric evidence for guard cell photosystems

    SciTech Connect

    Vaughn, K.C.; Outlaw, W.H. Jr.

    1983-01-01

    Evidence for photosynthetic linear electron transport in guard cells was obtained with two sensitive methods of high spacial resolution. Light-dependent diaminobenzidine oxidation (an indicator of PSI) and DCMU-sensitive, light-dependent thiocarbamyl nitroblue tetrazolium reduction (an indicator of PSII) were observed in guard cell plastids of Hordeum vulgare L. cv Himalaya using electron microscopic cytochemical procedures. DCMU-sensitive Chl a fluorescence induction (an indicator of PSII) was detected in individual guard cell pairs of Vicia faba L. cv Longpod using an ultramicrofluorometer. At least for these species, we conclude these results are proof for the presence of PSII in guard cell chloroplasts, which until now has been somewhat controversial. 31 references, 2 figures.

  7. Biochemical evidence for programmed cell death in rabbit uterine epithelium.

    PubMed Central

    Rotello, R. J.; Hocker, M. B.; Gerschenson, L. E.

    1989-01-01

    Uterine epithelial cell proliferation, differentiation, and death are known to be regulated by estrogen and progesterone. The authors investigated a specific pattern of cell death called apoptosis, or programmed cell death, which is biochemically characterized by a specific pattern of DNA degradation. DNA isolated from endometrium of ovariectomized pseudopregnant rabbits showed a pattern of DNA cleavage at internucleosomal locations. In comparison, DNA from the endometrium of non-ovariectomized animals, as well as several other organs, did not exhibit that pattern. This biochemical evidence supports previous and present morphologic data and correlates with it. Under the experimental conditions used, only the uterine epithelial compartment of the endometrium shows apoptotic cell death, which is absent in the stromal compartment. Images Figure 1 Figure 2 PMID:2923180

  8. Personal development plans and self‐directed learning for healthcare professionals: are they evidence based?

    PubMed Central

    Jennings, Stephen F

    2007-01-01

    The UK chief medical officer's recommendations for the re‐licensing and performance management of doctors will mean a move from a formative towards a summative role for appraisal and its adjunct, the personal development plan. Where does this leave medical educators trying to promote reflective learning? It is taken for granted that self‐directed learning is the sine qua non of all adult learning. But is it? This review re‐evaluates self‐directed learning and its corollary, the personal development plan, in the light of the chief medical officer's report, seeking the evidence behind today's accepted educational practice. It discovers a reality which challenges assumptions long enshrined in medical education. PMID:17675544

  9. Cancer stem cells in lung cancer: Evidence and controversies.

    PubMed

    Alamgeer, Muhammad; Peacock, Craig D; Matsui, William; Ganju, Vinod; Watkins, D Neil

    2013-07-01

    The cancer stem cell (CSC) model is based on a myriad of experimental and clinical observations suggesting that the malignant phenotype is sustained by a subset of cells characterized by the capacity for self-renewal, differentiation and innate resistance to chemotherapy and radiation. CSC may be responsible for disease recurrence after definitive therapy and may therefore be functionally synonymous with minimal residual disease. Similar to other solid tumours, several putative surface markers for lung CSC have been identified, including CD133 and CD44. In addition, expression and/or activity of the cytoplasmic enzyme aldehyde dehydrogenase ALDH and capacity of cells to exclude membrane permeable dyes (known as the 'side population') correlate with stem-like function in vitro and in vivo. Embryonic stem cell pathways such as Hedgehog, Notch and WNT may also be active in lung cancers stem cells and therefore may be therapeutically targetable for maintenance therapy in patients achieving a complete response to surgery, radiotherapy or chemotherapy. This paper will review the evidence regarding the existence and function of lung CSC in the context of the experimental and clinical evidence and discuss some ongoing controversies regarding this model.

  10. A development of direct hydrazine/hydrogen peroxide fuel cell

    NASA Astrophysics Data System (ADS)

    Lao, Shao Jiang; Qin, Hai Ying; Ye, Li Qiang; Liu, Bin Hong; Li, Zhou Peng

    A direct hydrazine fuel cell using H 2O 2 as the oxidizer has been developed. The N 2H 4/H 2O 2 fuel cell is assembled by using Ni-Pt/C composite catalyst as the anode catalyst, Au/C as the cathode catalyst, and Nafion membrane as the electrolyte. Both anolyte and catholyte show significant influences on cell voltage and cell performance. The open-circuit voltage of the N 2H 4/H 2O 2 fuel cell reaches up to 1.75 V when using alkaline N 2H 4 solution as the anolyte and acidic H 2O 2 solution as the catholyte. A maximum power density of 1.02 W cm -2 has been achieved at operation temperature of 80 °C. The number of electrons exchanged in the H 2O 2 reduction reaction on Au/C catalyst is 2.

  11. Direct hydrogen fuel cell systems for hybrid vehicles

    NASA Astrophysics Data System (ADS)

    Ahluwalia, Rajesh K.; Wang, X.

    Hybridizing a fuel cell system with an energy storage system offers an opportunity to improve the fuel economy of the vehicle through regenerative braking and possibly to increase the specific power and decrease the cost of the combined energy conversion and storage systems. Even in a hybrid configuration it is advantageous to operate the fuel cell system in a load-following mode and use the power from the energy storage system when the fuel cell alone cannot meet the power demand. This paper discusses an approach for designing load-following fuel cell systems for hybrid vehicles and illustrates it by applying it to pressurized, direct hydrogen, polymer-electrolyte fuel cell (PEFC) systems for a mid-size family sedan. The vehicle level requirements relative to traction power, response time, start-up time and energy conversion efficiency are used to select the important parameters for the PEFC stack, air management system, heat rejection system and the water management system.

  12. Thermodynamic properties of direct methanol polymer electrolyte fuel cell

    NASA Astrophysics Data System (ADS)

    Seong, Ji Yun; Bae, Young Chan; Sun, Yang Kook

    A new semi-empirical model is established to describe the cell voltage of a direct methanol fuel cell (DMFC) as a function of current density. The model equation is validated experimental data over a wide range of a methanol concentration and temperatures. A number of existing models are semi-empirical. They, however, have a serious mathematical defect. When the current density, j, becomes zero, the equation should reduce to the open circuit voltage, E0. These models, however, do not meet the mathematical boundary condition. The proposed model focuses on very unfavorable conditions for the cell operation, i.e. low methanol solution concentrations and relatively low cell temperatures. A newly developed semi-empirical equation with reasonable boundary conditions includes the methanol crossover effect that plays a major role in determining the cell voltage of DMFC. Also, it contains methanol activity based on thermodynamic functions to represent methanol crossover effect.

  13. IL-27 Directly Enhances Germinal Center B Cell Activity and Potentiates Lupus in Sanroque Mice.

    PubMed

    Vijayan, Dipti; Mohd Redzwan, Norhanani; Avery, Danielle T; Wirasinha, Rushika C; Brink, Robert; Walters, Giles; Adelstein, Stephen; Kobayashi, Masao; Gray, Paul; Elliott, Michael; Wong, Melanie; King, Cecile; Vinuesa, Carola G; Ghilardi, Nico; Ma, Cindy S; Tangye, Stuart G; Batten, Marcel

    2016-10-15

    Germinal centers (GC) give rise to high-affinity and long-lived Abs and are critical in immunity and autoimmunity. IL-27 supports GCs by promoting survival and function of T follicular helper cells. We demonstrate that IL-27 also directly enhances GC B cell function. Exposure of naive human B cells to rIL-27 during in vitro activation enhanced their differentiation into CD20(+)CD38(+)CD27(low)CD95(+)CD10(+) cells, consistent with the surface marker phenotype of GC B cells. This effect was inhibited by loss-of-function mutations in STAT1 but not STAT3 To extend these findings, we studied the in vivo effects of IL-27 signals to B cells in the GC-driven Roquin(san/san) lupus mouse model. Il27ra(-/-)Roquin(san/san) mice exhibited significantly reduced GCs, IgG2a(c)(+) autoantibodies, and nephritis. Mixed bone marrow chimeras confirmed that IL-27 acts through B cell- and CD4(+) T cell-intrinsic mechanisms to support GCs and alter the production of pathogenic Ig isotypes. To our knowledge, our data provide the first evidence that IL-27 signals directly to B cells promote GCs and support the role of IL-27 in lupus.

  14. Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6

    PubMed Central

    Draper, Lindsey M.; Kwong, Mei Li; Gros, Alena; Stevanović, Sanja; Tran, Eric; Kerkar, Sid; Raffeld, Mark; Rosenberg, Steven A.; Hinrichs, Christian S.

    2015-01-01

    Purpose The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in principle ideal immunotherapeutic targets, but evidence that T cells specific for these antigens can recognize and kill HPV+ tumor cells is limited. We sought to determine if TCR gene engineered T cells directed against an HPV oncoprotein can successfully target HPV+ tumor cells. Experimental design T cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22-month disease-free interval after her second resection of distant metastatic anal cancer. T cells genetically engineered to express an oncoprotein-specific TCR from this patient’s tumor-infiltrating T cells were tested for specific reactivity against HPV+ epithelial tumor cells. Results We identified, from an excised metastatic anal cancer tumor, T cells that recognized an HLA-A*02:01-restricted epitope of HPV-16 E6. The frequency of the dominant T cell clonotype from these cells was approximately 400-fold greater in the patient’s tumor than in her peripheral blood. T cells genetically engineered to express the TCR from this clonotype displayed high avidity for an HLA-A*02:01-restricted epitope of HPV-16, and they showed specific recognition and killing of HPV-16+ cervical, and head and neck cancer cell lines. Conclusion These findings demonstrate that HPV-16+ tumors can be targeted by E6-specific TCR gene engineered T cells, and they provide the foundation for a novel cellular therapy directed against HPV-16+ malignancies including cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. PMID:26429982

  15. Distractor devaluation effect in the attentional blink: direct evidence for distractor inhibition.

    PubMed

    Kihara, Ken; Yagi, Yoshihiko; Takeda, Yuji; Kawahara, Jun I

    2011-02-01

    When two targets (T1 and T2) are embedded in rapid serial visual presentation (RSVP), T2 is often missed (attentional blink, AB) if T2 follows T1 by less than 500 ms. Some have proposed that inhibition of a distractor following T1 contributes to the AB, but no direct evidence supports this proposal. This study examined distractor inhibition by assessing a distractor devaluation effect where inhibited items were evaluated less positively than controls. Experiments 1 and 2 showed that a distractor presented just after T1 was evaluated less favorably when T2 was misidentified, independently of stimulus characteristics. Experiment 3 produced distractor devaluation in T2 incorrect trials when the evaluated distractor was the second item after T1. In contrast, a distractor presented before T1 was not devaluated (Experiment 4). Experiment 5 demonstrated that participants could not recognize presented distractors after an RSVP task, rejecting the possibility that memorized distractors were devalued. Results show a relationship between the devaluation of distractors following T1 and the AB, providing the first direct evidence of the distractor inhibition during the AB.

  16. The first direct evidence of pre-columbian sources of palygorskite for Maya Blue

    USGS Publications Warehouse

    Arnold, Dean E.; Bohor, Bruce F.; Neff, Hector; Feinman, Gary M.; Williams, Patrick Ryan; Dussubieux, Laure; Bishop, Ronald

    2012-01-01

    Maya Blue, a nano-structured clay–organic complex of palygorskite and indigo, was used predominantly before the Spanish Conquest. It has fascinated chemists, material scientists, archaeologists and art historians for decades because it is resistant to the effect of acids, alkalis, and other reagents, and its rich color has persisted for centuries in the harsh tropical climate of southern Mesoamerica. One of its components, palygorskite, is part of modern Maya indigenous knowledge, and ethnohistoric and archaeological data suggest that its modern sources were probably utilized in Prehispanic times. Yet no direct evidence verifies that palygorskite was actually mined from these sources to make Maya Blue. Here we characterize these sources compositionally, and compare our analyses to those of Maya Blue from Chichén Itzá and Palenque. We demonstrate that the palygorskite in most of these samples came from modern mines, providing the first direct evidence for the use of these sources for making Maya Blue. These findings reveal that modern Maya indigenous knowledge about palygorskite, its mining, and its source locations, is at least seven centuries old.

  17. Laetoli Footprints Preserve Earliest Direct Evidence of Human-Like Bipedal Biomechanics

    PubMed Central

    Raichlen, David A.; Gordon, Adam D.; Harcourt-Smith, William E. H.; Foster, Adam D.; Haas, Wm. Randall

    2010-01-01

    Background Debates over the evolution of hominin bipedalism, a defining human characteristic, revolve around whether early bipeds walked more like humans, with energetically efficient extended hind limbs, or more like apes with flexed hind limbs. The 3.6 million year old hominin footprints at Laetoli, Tanzania represent the earliest direct evidence of hominin bipedalism. Determining the kinematics of Laetoli hominins will allow us to understand whether selection acted to decrease energy costs of bipedalism by 3.6 Ma. Methodology/Principal Findings Using an experimental design, we show that the Laetoli hominins walked with weight transfer most similar to the economical extended limb bipedalism of humans. Humans walked through a sand trackway using both extended limb bipedalism, and more flexed limb bipedalism. Footprint morphology from extended limb trials matches weight distribution patterns found in the Laetoli footprints. Conclusions These results provide us with the earliest direct evidence of kinematically human-like bipedalism currently known, and show that extended limb bipedalism evolved long before the appearance of the genus Homo. Since extended-limb bipedalism is more energetically economical than ape-like bipedalism, energy expenditure was likely an important selection pressure on hominin bipeds by 3.6 Ma. PMID:20339543

  18. Evidence for apoptotic cell death in Alzheimer's disease.

    PubMed

    Smale, G; Nichols, N R; Brady, D R; Finch, C E; Horton, W E

    1995-06-01

    We provide evidence for apoptosis in Alzheimer's disease using the in situ labeling technique TUNEL (terminal transferase-mediated dUTP-biotin nick end labeling). The technique specifically detects apoptotic cells by utilizing terminal transferase to incorporate biotinylated nucleotides into the fragmented DNA of apoptotic cells. The labeled cells are visualized by reaction with avidin peroxidase and a suitable substrate. Sections from the hippocampus of Alzheimer-diseased (AD) brains and non-AD brains were examined for apoptosis. While considerable variation in the quantity of apoptotic cells was observed among individual samples, the incidence of apoptosis in AD brains was elevated in comparison to age-matched, non-AD brains in specific regions of the hippocampal formation. Immunostaining indicated that both neurons and astrocytes were undergoing apoptosis, although the majority of the TUNEL-positive cells appeared to be glial, based on the location of the stained cells. These data suggest that apoptosis may be involved in both the primary neuronal cell loss and in the glial response that is a component of AD.

  19. The Nuclear Option: Evidence Implicating the Cell Nucleus in Mechanotransduction.

    PubMed

    Szczesny, Spencer E; Mauck, Robert L

    2017-02-01

    Biophysical stimuli presented to cells via microenvironmental properties (e.g., alignment and stiffness) or external forces have a significant impact on cell function and behavior. Recently, the cell nucleus has been identified as a mechanosensitive organelle that contributes to the perception and response to mechanical stimuli. However, the specific mechanotransduction mechanisms that mediate these effects have not been clearly established. Here, we offer a comprehensive review of the evidence supporting (and refuting) three hypothetical nuclear mechanotransduction mechanisms: physical reorganization of chromatin, signaling at the nuclear envelope, and altered cytoskeletal structure/tension due to nuclear remodeling. Our goal is to provide a reference detailing the progress that has been made and the areas that still require investigation regarding the role of nuclear mechanotransduction in cell biology. Additionally, we will briefly discuss the role that mathematical models of cell mechanics can play in testing these hypotheses and in elucidating how biophysical stimulation of the nucleus drives changes in cell behavior. While force-induced alterations in signaling pathways involving lamina-associated polypeptides (LAPs) (e.g., emerin and histone deacetylase 3 (HDAC3)) and transcription factors (TFs) located at the nuclear envelope currently appear to be the most clearly supported mechanism of nuclear mechanotransduction, additional work is required to examine this process in detail and to more fully test alternative mechanisms. The combination of sophisticated experimental techniques and advanced mathematical models is necessary to enhance our understanding of the role of the nucleus in the mechanotransduction processes driving numerous critical cell functions.

  20. Direct Visualization of De novo Lipogenesis in Single Living Cells

    NASA Astrophysics Data System (ADS)

    Li, Junjie; Cheng, Ji-Xin

    2014-10-01

    Increased de novo lipogenesis is being increasingly recognized as a hallmark of cancer. Despite recent advances in fluorescence microscopy, autoradiography and mass spectrometry, direct observation of de novo lipogenesis in living systems remains to be challenging. Here, by coupling stimulated Raman scattering (SRS) microscopy with isotope labeled glucose, we were able to trace the dynamic metabolism of glucose in single living cells with high spatial-temporal resolution. As the first direct visualization, we observed that glucose was largely utilized for lipid synthesis in pancreatic cancer cells, which occurs at a much lower rate in immortalized normal pancreatic epithelial cells. By inhibition of glycolysis and fatty acid synthase (FAS), the key enzyme for fatty acid synthesis, we confirmed the deuterium labeled lipids in cancer cells were from de novo lipid synthesis. Interestingly, we also found that prostate cancer cells exhibit relatively lower level of de novo lipogenesis, but higher fatty acid uptake compared to pancreatic cancer cells. Together, our results demonstrate a valuable tool to study dynamic lipid metabolism in cancer and other disorders.

  1. Recent advances in high-performance direct methanol fuel cells

    SciTech Connect

    Narayanan, S.R.; Chun, W.; Valdez, T.I.

    1996-12-31

    Direct methanol fuel cells for portable power applications have been advanced significantly under DARPA- and ARO-sponsored programs over the last five years. A liquid-feed direct methanol fuel cell developed under these programs, employs a proton exchange membrane as electrolyte and operates on aqueous solutions of methanol with air or oxygen as the oxidant. Power densities as high as 320 mW/cm{sup 2} have been demonstrated. Demonstration of five-cell stack based on the liquid-feed concept have been successfully performed by Giner Inc. and the Jet Propulsion Laboratory. Over 2000 hours of life-testing have been completed on these stacks. These fuel cells have been also been demonstrated by USC to operate on alternate fuels such as trimethoxymethane, dimethoxymethane and trioxane. Reduction in the parasitic loss of fuel across the fuel cell, a phenomenon termed as {open_quotes}fuel crossover{close_quotes} has been achieved using polymer membranes developed at USC. As a result efficiencies as high as 40% is considered attainable with this type of fuel cell. The state-of-development has reached a point where it is now been actively considered for stationary, portable and transportation applications. The research and development issues have been the subject of several previous articles and the present article is an attempt to summarize the key advances in this technology.

  2. Direct effect of bevacizumab on glioblastoma cell lines in vitro.

    PubMed

    Simon, Thomas; Coquerel, Bérénice; Petit, Alexandre; Kassim, Yusra; Demange, Elise; Le Cerf, Didier; Perrot, Valérie; Vannier, Jean-Pierre

    2014-12-01

    Bevacizumab is a humanized monoclonal antibody directed against the pro-angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non-mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Investigation of how bevacizumab interacts with glioblastoma cells and the resulting downstream signaling pathways will help targeting populations of resistant glioblastoma cells.

  3. Cell-Substrate Interactions Feedback to Direct Cell Migration along or against Morphological Polarization

    PubMed Central

    Kumar, Girish; Ho, Chia-Chi; Co, Carlos C.

    2015-01-01

    In response to external stimuli, cells polarize morphologically into teardrop shapes prior to moving in the direction of their blunt leading edge through lamellipodia extension and retraction of the rear tip. This textbook description of cell migration implies that the initial polarization sets the direction of cell migration. Using microfabrication techniques to control cell morphologies and the direction of migration without gradients, we demonstrate that after polarization, lamelipodia extension and attachment can feedback to change and even reverse the initial morphological polarization. Cells do indeed migrate faster in the direction of their morphologically polarization. However, feedback from subsequent lamellipodia extension and attachment can be so powerful as to induce cells to reverse and migrate against their initial polarization, albeit at a slower speed. Constitutively active mutants of RhoA show that RhoA stimulates cell motility when cells are guided either along or against their initial polarization. Cdc42 activation and inhibition, which results in loss of directional motility during chemotaxis, only reduces the speed of migration without altering the directionality of migration on the micropatterns. These results reveal significant differences between substrate directed cell migration and that induced by chemotactic gradients. PMID:26186588

  4. Multifactorial Optimizations for Directing Endothelial Fate from Stem Cells

    PubMed Central

    Madfis, Nicole; Wong, Lian; Zamora, Jose; White, Nicholas; Reyes, Samuel; Burns, Andrew B.; Gopinathan, Ajay

    2016-01-01

    Embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells are attractive in vitro models of vascular development, therapeutic angiogenesis, and tissue engineering. However, distinct ESC and iPS cell lines respond differentially to the same microenvironmental factors. Developing improved/optimized differentiation methodologies tailored/applicable in a number of distinct iPS and ESC lines remains a challenge in the field. Currently published methods for deriving endothelial cells (EC) robustly generate high numbers of endothlelial progenitor cells (EPC) within a week, but their maturation to definitive EC is much more difficult, taking up to 2 months and requiring additional purification. Therefore, we set out to examine combinations/levels of putative EC induction factors—utilizing our stage-specific chemically-defined derivation methodology in 4 ESC lines including: kinetics, cell seeding density, matrix signaling, as well as medium treatment with vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The results indicate that temporal development in both early and late stages is the most significant factor generating the desired cells. The generation of early Flk-1+/KDR+ vascular progenitor cells (VPC) from pluripotent ESC is directed predominantly by high cell seeding density and matrix signaling from fibronectin, while VEGF supplementation was NOT statistically significant in more than one cell line, especially with fibronectin matrix which sequesters autocrine VEGF production by the differentiating stem cells. Although some groups have shown that the GSK3-kinase inhibitor (CHIR) can facilitate EPC fate, it hindered the generation of KDR+ cells in our preoptimized medium formulations. The methods summarized here significantly increased the production of mature vascular endothelial (VE)-cadherin+ EC, with up to 93% and 57% purity from mouse and human ESC, respectively, before VE-cadherin+ EC purification. PMID:27907001

  5. Social Network Analysis Shows Direct Evidence for Social Transmission of Tool Use in Wild Chimpanzees

    PubMed Central

    Hobaiter, Catherine; Poisot, Timothée; Zuberbühler, Klaus; Hoppitt, William; Gruber, Thibaud

    2014-01-01

    Social network analysis methods have made it possible to test whether novel behaviors in animals spread through individual or social learning. To date, however, social network analysis of wild populations has been limited to static models that cannot precisely reflect the dynamics of learning, for instance, the impact of multiple observations across time. Here, we present a novel dynamic version of network analysis that is capable of capturing temporal aspects of acquisition—that is, how successive observations by an individual influence its acquisition of the novel behavior. We apply this model to studying the spread of two novel tool-use variants, “moss-sponging” and “leaf-sponge re-use,” in the Sonso chimpanzee community of Budongo Forest, Uganda. Chimpanzees are widely considered the most “cultural” of all animal species, with 39 behaviors suspected as socially acquired, most of them in the domain of tool-use. The cultural hypothesis is supported by experimental data from captive chimpanzees and a range of observational data. However, for wild groups, there is still no direct experimental evidence for social learning, nor has there been any direct observation of social diffusion of behavioral innovations. Here, we tested both a static and a dynamic network model and found strong evidence that diffusion patterns of moss-sponging, but not leaf-sponge re-use, were significantly better explained by social than individual learning. The most conservative estimate of social transmission accounted for 85% of observed events, with an estimated 15-fold increase in learning rate for each time a novice observed an informed individual moss-sponging. We conclude that group-specific behavioral variants in wild chimpanzees can be socially learned, adding to the evidence that this prerequisite for culture originated in a common ancestor of great apes and humans, long before the advent of modern humans. PMID:25268798

  6. DIRECTED DIFFERENTIATION OF EMBRYONIC STEM CELLS INTO BLADDER TISSUE

    PubMed Central

    Oottamasathien, Siam; Wang, YongQing; Williams, Karin; Franco, Omar E.; Wills, Marcia L.; Thomas, John C.; Saba, Katrina; Sharif-Afshar, Ali-Reza; Makari, John H.; Bhowmick, Neil A; DeMarco, Romano T.; Hipkens, Susan; Magnuson, Mark; Brock, John W.; Hayward, Simon W.; Pope, John C.; Matusik, Robert J.

    2007-01-01

    Manipulatable models of bladder development which interrogate specific pathways are badly needed. Such models will allow a systematic investigation of the multitude of pathologies which result from developmental defects of the urinary bladder. In the present communication, we describe a model in which mouse embryonic stem (ES) cells are directed to differentiate to form bladder tissue by specific interactions with fetal bladder mesenchyme. This model allows us to visualize the various stages in the differentiation of urothelium from ES cells, including the commitment to an endodermal cell lineage, with the temporal profile characterized by examining the induction of specific endodermal transcription factors (Foxa1 and Foxa2). In addition, final functional urothelial differentiation was characterized by examining uroplakin expression. It is well established that ES cells will spontaneously develop teratomas when grown within immunocompromised mouse hosts. We determined the specific mesenchymal to ES cell ratios necessary to dictate organ-specific differentiation while completely suppressing teratomatous growth. Embryonic mesenchyme is well established as an inductive tissue which dictates organ-specific programming of epithelial tissues. The present study demonstrates that embryonic bladder mesenchyme can also steer ES cells towards developing specific endodermal derived urothelium. These approaches allow us to capture specific stages of stem cell differentiation and to better define stem cell hierarchies. PMID:17289017

  7. Mesenchymal Stem Cells Induce Directional Migration of Invasive Breast Cancer Cells through TGF-β

    PubMed Central

    McAndrews, Kathleen M.; McGrail, Daniel J.; Ravikumar, Nithin; Dawson, Michelle R.

    2015-01-01

    Mesenchymal stem cells (MSCs) are recruited to the tumor microenvironment and influence tumor progression; however, how MSCs induce the invasion of cancer cells is not completely understood. Here, we used a 3D coculture model to determine how MSCs affect the migration of invasive breast cancer cells. Coculture with MSCs increases the elongation, directional migration, and traction generation of breast cancer cells. MSC-induced directional migration directly correlates with traction generation and is mediated by transforming growth factor β (TGF-β) and the migratory proteins rho-associated kinase, focal adhesion kinase, and matrix metalloproteinases. Treatment with MSC conditioned media or recombinant TGF-β1 elicits a similar migration response to coculture. Taken together, this work suggests TGF-β is secreted by MSCs, leading to force-dependent directional migration of invasive breast cancer cells. These pathways may be potential targets for blocking cancer cell invasion and subsequent metastasis. PMID:26585689

  8. European Working Time Directive and doctors’ health: a systematic review of the available epidemiological evidence

    PubMed Central

    Rodriguez-Jareño, Maria Cruz; Demou, Evangelia; Vargas-Prada, Sergio; Sanati, Kaveh A; Škerjanc, Alenka; Reis, Pedro G; Helimäki-Aro, Ritva; Macdonald, Ewan B; Serra, Consol

    2014-01-01

    Objective To summarise the available scientific evidence on the health effects of exposure to working beyond the limit number of hours established by the European Working Time Directive (EWTD) on physicians. Design A systematic literature search was conducted in PubMed and EMBASE. Study selection, quality appraisal and data extraction were carried out by independent pairs of researchers using pre-established criteria. Setting Physicians of any medical, surgical or community specialty, working in any possible setting (hospitals, primary healthcare, etc), as well as trainees, residents, junior house officers or postgraduate interns, were included. Participants The total number of participants was 14 338. Primary and secondary outcome measures Health effects classified under the International Classification of Diseases (ICD-10). Results Over 3000 citations and 110 full articles were reviewed. From these, 11 studies of high or intermediate quality carried out in North America, Europe and Japan met the inclusion criteria. Six studies included medical residents, junior doctors or house officers and the five others included medical specialists or consultants, medical, dental, and general practitioners and hospital physicians. Evidence of an association was found between percutaneous injuries and road traffic accidents with extended long working hours (LWH)/days or very LWH/weeks. The evidence was insufficient for mood disorders and general health. No studies on other health outcomes were identified. Conclusions LWH could increase the risk of percutaneous injuries and road traffic accidents, and possibly other incidents at work through the same pathway. While associations are clear, the existing evidence does not allow for an established causal or ‘dose–response’ relationship between LWH and incidents at work, or for a threshold number of extended hours above which there is a significantly higher risk and the hours physicians could work and remain safe and healthy

  9. Direct evidence of trophic interactions among apex predators in the Late Triassic of western North America.

    PubMed

    Drumheller, Stephanie K; Stocker, Michelle R; Nesbitt, Sterling J

    2014-11-01

    Hypotheses of feeding behaviors and community structure are testable with rare direct evidence of trophic interactions in the fossil record (e.g., bite marks). We present evidence of four predation, scavenging, and/or interspecific fighting events involving two large paracrocodylomorphs (='rauisuchians') from the Upper Triassic Chinle Formation (∼220-210 Ma). The larger femur preserves a rare history of interactions with multiple actors prior to and after death of this ∼8-9-m individual. A large embedded tooth crown and punctures, all of which display reaction tissue formed through healing, record evidence of a failed attack on this individual. The second paracrocodylomorph femur exhibits four unhealed bite marks, indicating the animal either did not survive the attack or was scavenged soon after death. The combination of character states observed (e.g., morphology of the embedded tooth, 'D'-shaped punctures, evidence of bicarination of the marking teeth, spacing of potentially serial marks) indicates that large phytosaurs were actors in both cases. Our analysis of these specimens demonstrates phytosaurs targeted large paracrocodylomorphs in these Late Triassic ecosystems. Previous distinctions between 'aquatic' and 'terrestrial' Late Triassic trophic structures were overly simplistic and built upon mistaken paleoecological assumptions; we show they were intimately connected at the highest trophic levels. Our data also support that size cannot be the sole factor in determining trophic status. Furthermore, these marks provide an opportunity to start exploring the seemingly unbalanced terrestrial ecosystems from the Late Triassic of North America, in which large carnivores far outnumber herbivores in terms of both abundance and diversity.

  10. Single passive direct methanol fuel cell supplied with pure methanol

    NASA Astrophysics Data System (ADS)

    Feng, Ligang; Zhang, Jing; Cai, Weiwei; Liang, Liang; Xing, Wei; Liu, Changpeng

    2011-03-01

    A new single passive direct methanol fuel cell (DMFC) supplied with pure methanol is designed, assembled and tested using a pervaporation membrane (PM) to control the methanol transport. The effect of the PM size on the fuel cell performances and the constant current discharge of the fuel cell with one-fueling are studied. The results show that the fuel cell with PM 9 cm2 can yield a maximum power density of about 21 mW cm-2, and a stable performances at a discharge current of 100 mA can last about 45 h. Compared with DMFC supplied with 3 M methanol solution, the energy density provided by this new DMFC has increased about 6 times.

  11. Electrophysiological Evidence for Intrinsic Pacemaker Currents in Crayfish Parasol Cells

    PubMed Central

    Mellon, DeForest

    2016-01-01

    I used sharp intracellular electrodes to record from parasol cells in the semi-isolated crayfish brain to investigate pacemaker currents. Evidence for the presence of the hyperpolarization-activated inward rectifier potassium current was obtained in about half of the parasol cells examined, where strong, prolonged hyperpolarizing currents generated a slowly-rising voltage sag, and a post-hyperpolarization rebound. The amplitudes of both the sag voltage and the depolarizing rebound were dependent upon the strength of the hyperpolarizing current. The voltage sag showed a definite threshold and was non-inactivating. The voltage sag and rebound depolarization evoked by hyperpolarization were blocked by the presence of 5–10 mM Cs2+ ions, 10 mM tetraethyl ammonium chloride, and 10 mM cobalt chloride in the bathing medium, but not by the drug ZD 7288. Cs+ ions in normal saline in some cells caused a slight increase in mean resting potential and a reduction in spontaneous burst frequency. Many of the neurons expressing the hyperpolarization-activated inward potassium current also provided evidence for the presence of the transient potassium current IA, which was inferred from experimental observations of an increased latency of post-hyperpolarization response to a depolarizing step, compared to the response latency to the depolarization alone. The latency increase was reduced in the presence of 4-aminopyridine (4-AP), a specific blocker of IA. The presence of 4-AP in normal saline also induced spontaneous bursting in parasol cells. It is conjectured that, under normal physiological conditions, these two potassium currents help to regulate burst generation in parasol cells, respectively, by helping to maintain the resting membrane potential near a threshold level for burst generation, and by regulating the rate of rise of membrane depolarizing events leading to burst generation. The presence of post-burst hyperpolarization may depend upon IA channels in parasol cells

  12. Novel mitochondrial extensions provide evidence for a link between microtubule-directed movement and mitochondrial fission

    SciTech Connect

    Bowes, Timothy; Gupta, Radhey S.

    2008-11-07

    Mitochondrial dynamics play an important role in a large number of cellular processes. Previously, we reported that treatment of mammalian cells with the cysteine-alkylators, N-ethylmaleimide and ethacrynic acid, induced rapid mitochondrial fusion forming a large reticulum approximately 30 min after treatment. Here, we further investigated this phenomenon using a number of techniques including live-cell confocal microscopy. In live cells, drug-induced fusion coincided with a cessation of fast mitochondrial movement which was dependent on microtubules. During this loss of movement, thin mitochondrial tubules extending from mitochondria were also observed, which we refer to as 'mitochondrial extensions'. The formation of these mitochondrial extensions, which were not observed in untreated cells, depended on microtubules and was abolished by pretreatment with nocodazole. In this study, we provide evidence that these extensions result from of a block in mitochondrial fission combined with continued application of motile force by microtubule-dependent motor complexes. Our observations strongly suggest the existence of a link between microtubule-based mitochondrial trafficking and mitochondrial fission.

  13. Process-Induced Cell Injury in Laser Direct Writing of Human Colon Cancer Cells.

    PubMed

    Lin, Yafu; Huang, Guohui; Huang, Yong; Tzeng, Tzuen-Rong J; Chrisey, Douglas B

    2010-03-19

    Matrix-assisted pulsed-laser evaporation direct-write has emerged as a promising technique for biological construct fabrication. The posttransfer cell viability in matrix-assisted pulsed-laser evaporation direct-write depends on various operating conditions such as the applied laser fluence. To date, the effects of operating conditions such as laser fluence, direct-writing height, and cell density on the posttransfer cell viability have not been well elucidated. This study investigates the effects of operating conditions on the posttransfer cell viability in laser direct writing of human colon cancer HT-29 cells. It has been observed that (1) the HT-29 cell viability decreases from 95% to 78% as the laser fluence increases from 258 to 1482 mJ/cm(2), and the posttransfer cell proliferation capacity does not vary significantly as the laser fluence changes; (2) the direct-writing height does not have noticeable effect on the posttransfer cell viability under low laser fluences (258 and 869 mJ/cm(2)). However, a larger height (such as 29.3 mm) led to an almost 8% viability improvement compared with that of 16.6 mm under a high laser fluence (1482 mJ/cm(2)); and (3) the posttransfer cell viability is not dependent on the cell density for a range from 1 × 10(6) to 1 × 10(7) cells/mL.

  14. Evidence for a direct involvement of hMSH5 in promoting ionizing radiation induced apoptosis

    SciTech Connect

    Tompkins, Joshua D.; Wu, Xiling; Chu, Yen-Lin; Her, Chengtao

    2009-08-15

    Although increasing evidence has suggested that the hMSH5 protein plays an important role in meiotic and mitotic DNA recombinational repair, its precise functions in recombination and DNA damage response are presently elusive. Here we show that the interaction between hMSH5 and c-Abl confers ionizing radiation (IR)-induced apoptotic response by promoting c-Abl activation and p73 accumulation, and these effects are greatly enhanced in cells expressing hMSH5{sup P29S} (i.e. the hMSH5 variant possessing a proline to serine change within the N-terminal (Px){sub 5} dipeptide repeat). Our current study provides the first evidence that the (Px){sub 5} dipeptide repeat plays an important role in modulating the interaction between hMSH5 and c-Abl and alteration of this dipeptide repeat in hMSH5{sup P29S} leads to increased IR sensitivity owing to enhanced caspase-3-mediated apoptosis. In addition, RNAi-mediated hMSH5 silencing leads to the reduction of apoptosis in IR-treated cells. In short, this study implicates a role for hMSH5 in DNA damage response involving c-Abl and p73, and suggests that mutations impairing this process could significantly affect normal cellular responses to anti-cancer treatments.

  15. On the evidence for clustering in the arrival directions of AGASA's ultrahigh energy cosmic rays

    NASA Astrophysics Data System (ADS)

    Finley, Chad B.; Westerhoff, Stefan

    2004-07-01

    Previous analyses of cosmic rays above 4 × 10 19 eV observed by the AGASA experiment have suggested that their arrival directions may be clustered. However, estimates of the chance probability of this clustering signal vary from 10 -2 to 10 -6 and beyond. It is essential that the strength of this evidence be well understood in order to compare it with anisotropy studies in other cosmic ray experiments. We apply two methods for extracting a meaningful significance from this data set: one can scan for the cuts which optimize the clustering signal, using simulations to determine the appropriate statistical penalty for the scan. This analysis finds a chance probability of about 0.3%. Alternatively, one can optimize the cuts with a first set of data, and then apply them to the remaining data directly without statistical penalty. One can extend the statistical power of this test by considering cross-correlation between the initial data and the remaining data, as long as the initial clustering signal is not included. While the scan is more useful in general, in the present case only splitting the data set offers an unbiased test of the clustering hypothesis. Using this test we find that the AGASA data is consistent at the 8% level with the null hypothesis of isotropically distributed arrival directions.

  16. Coordinated vigilance provides evidence for direct reciprocity in coral reef fishes

    PubMed Central

    Brandl, Simon J.; Bellwood, David R.

    2015-01-01

    Reciprocity is frequently assumed to require complex cognitive abilities. Therefore, it has been argued that reciprocity may be restricted to animals that can meet these demands. Here, we provide evidence for the potential presence of direct reciprocity in teleost fishes. We demonstrate that in pairs of coral reef rabbitfishes (f. Siganidae), one fish frequently assumes an upright vigilance position in the water column, while the partner forages in small crevices in the reef substratum. Both behaviours are strongly coordinated and partners regularly alternate their positions, resulting in a balanced distribution of foraging activity. Compared to solitary individuals, fishes in pairs exhibit longer vigilance bouts, suggesting that the help provided to the partner is costly. In turn, fishes in pairs take more consecutive bites and penetrate deeper into crevices than solitary individuals, suggesting that the safety provided by a vigilant partner may outweigh initial costs by increasing foraging efficiency. Thus, the described system appears to meet all of the requirements for direct reciprocity. We argue that the nature of rabbitfish pairs provides favourable conditions for the establishment of direct reciprocity, as continuous interaction with the same partner, simultaneous needs, interdependence, and communication relax the cognitive demands of reciprocal cooperation. PMID:26403250

  17. Does the vestibular system contribute to head direction cell activity in the rat?

    NASA Technical Reports Server (NTRS)

    Brown, J. E.; Yates, B. J.; Taube, J. S.; Oman, C. M. (Principal Investigator)

    2002-01-01

    Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral mammillary nuclei (LMN), provide the neural substrate for the determination of head direction. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. However, vestibular inputs must be transformed considerably in order to signal head direction, and the neuronal circuitry that accomplishes this signal processing has not been fully established. Furthermore, it is unclear why the removal of vestibular inputs abolishes the directional sensitivity of HDC, as visual and other sensory inputs and motor feedback signals strongly affect the firing of these neurons and would be expected to maintain their directional-related activity. Further physiological studies will be required to establish the role of vestibular system in producing HDC responses, and anatomical studies are needed to determine the neural circuitry that mediates vestibular influences on determination of head direction.

  18. Trioxane: A Fuel For Direct-Oxidation Fuel Cells

    NASA Technical Reports Server (NTRS)

    Olah, George A.; Prakash, Surya G.; Narayanan, Sekharipuram R.; Vamos, Eugene; Surampudi, Subbarao

    1995-01-01

    Trioxane identified as high-energy, nontoxic, solid substitute for formaldehyde as water-soluble fuel for use in direct-oxidation fuel cells. Found to undergo facile electrochemical oxidation to water and carbon dioxide at platinum and platinum-alloy electrodes in liquid-feed-type fuel cells that contain acid electrolytes or solid proton-exchange membrane electrolytes. Exhibits less crossover than do such conventional fuels as methanol and formaldehyde. Being solid at ambient temperature, trioxane offers significant advantages in handling and transportation. Synthesized from natural gas with relative ease.

  19. Wire mesh current collectors for passive direct methanol fuel cells

    NASA Astrophysics Data System (ADS)

    Shrivastava, Naveen K.; Thombre, Shashikant B.; Motghare, Ramani V.

    2014-12-01

    This paper examines the feasibility of the stainless steel wire mesh as current collector in the passive direct methanol fuel cell (DMFCs-W). A novel single cell fixture is designed and fabricated. The cell performance is evaluated and compared with five different wire mesh current collectors. The supporting plates are optimized for every mesh. The performance of DMFCs-W is compared with the conventional passive DMFC which uses perforated metal plate as current collector (DMFC-P). The polarization tests and electrochemical impedance spectroscopy are performed to investigate the different aspects of the cell performance. The results reveal that the DMFCs-W yield better performance than the DMFC-P. Also, more uniform fuel distribution at catalyst layer and higher cell temperature is achieved with wire mesh current collectors. It is found that the wire mesh geometry has significant effect on the cell performance and the mesh made of relatively thick wires gives better cell performance. This study identifies the stainless steel wire mesh as promising material to be used as current collector and potential substitute to the perforated plate current collectors in the passive DMFC.

  20. Direct Visualization of DNA Replication Dynamics in Zebrafish Cells.

    PubMed

    Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Tamaru, Yutaka; Ogata, Shin; Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2015-12-01

    Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ∼ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells.

  1. Coordinated Switching of Bacterial Flagellar Motors: Evidence for Direct Motor-Motor Coupling?

    NASA Astrophysics Data System (ADS)

    Hu, Bo; Tu, Yuhai

    2013-04-01

    The swimming of Escherichia coli is powered by its multiple flagellar motors. Each motor spins either clockwise or counterclockwise, under the control of an intracellular regulator, CheY-P. There can be two mechanisms (extrinsic and intrinsic) to coordinate the switching of bacterial motors. The extrinsic one arises from the fact that different motors in the same cell sense a common input (CheY-P) which fluctuates near the motors’ response threshold. An alternative, intrinsic mechanism is direct motor-motor coupling which makes synchronized switching energetically favorable. Here, we develop simple models for both mechanisms and uncover their different hallmarks. A quantitative comparison to the recent experiments suggests that the direct coupling mechanism may be accountable for the observed sharp correlation between motors in a single Escherichia coli. Possible origins of this coupling (e.g., hydrodynamic interaction) are discussed.

  2. Direct methanol feed fuel cell with reduced catalyst loading

    NASA Technical Reports Server (NTRS)

    Kindler, Andrew (Inventor)

    1999-01-01

    Improvements to direct feed methanol fuel cells include new protocols for component formation. Catalyst-water repellent material is applied in formation of electrodes and sintered before application of ionomer. A membrane used in formation of an electrode assembly is specially pre-treated to improve bonding between catalyst and membrane. The improved electrode and the pre-treated membrane are assembled into a membrane electrode assembly.

  3. Experimental Design to Evaluate Directed Adaptive Mutation in Mammalian Cells

    PubMed Central

    Chiaro, Christopher R; May, Tobias

    2014-01-01

    Background We describe the experimental design for a methodological approach to determine whether directed adaptive mutation occurs in mammalian cells. Identification of directed adaptive mutation would have profound practical significance for a wide variety of biomedical problems, including disease development and resistance to treatment. In adaptive mutation, the genetic or epigenetic change is not random; instead, the presence and type of selection influences the frequency and character of the mutation event. Adaptive mutation can contribute to the evolution of microbial pathogenesis, cancer, and drug resistance, and may become a focus of novel therapeutic interventions. Objective Our experimental approach was designed to distinguish between 3 types of mutation: (1) random mutations that are independent of selective pressure, (2) undirected adaptive mutations that arise when selective pressure induces a general increase in the mutation rate, and (3) directed adaptive mutations that arise when selective pressure induces targeted mutations that specifically influence the adaptive response. The purpose of this report is to introduce an experimental design and describe limited pilot experiment data (not to describe a complete set of experiments); hence, it is an early report. Methods An experimental design based on immortalization of mouse embryonic fibroblast cells is presented that links clonal cell growth to reversal of an inactivating polyadenylation site mutation. Thus, cells exhibit growth only in the presence of both the countermutation and an inducing agent (doxycycline). The type and frequency of mutation in the presence or absence of doxycycline will be evaluated. Additional experimental approaches would determine whether the cells exhibit a generalized increase in mutation rate and/or whether the cells show altered expression of error-prone DNA polymerases or of mismatch repair proteins. Results We performed the initial stages of characterizing our system

  4. Angiotensin II directly impairs adipogenic differentiation of human preadipose cells.

    PubMed

    Palominos, Marisol M; Dünner, Natalia H; Wabitsch, Martin; Rojas, Cecilia V

    2015-10-01

    Angiotensin II reduces adipogenic differentiation of preadipose cells present in the stroma-vascular fraction of human adipose tissue, which also includes several cell types. Because of the ability of non-adipose lineage cells in the stroma-vascular fraction to respond to angiotensin II, it is not possible to unequivocally ascribe the anti-adipogenic response to a direct effect of this hormone on preadipose cells. Therefore, we used the human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell strain to investigate the consequences of angiotensin II treatment on adipogenic differentiation under serum-free conditions, by assessing expression of typical adipocyte markers perilipin and fatty acid-binding protein 4 (FABP4), at the transcript and protein level. Reverse transcription-polymerase chain reaction showed that perilipin and FABP4 transcripts were, respectively, reduced to 0.33 ± 0.07 (P < 0.05) and 0.41 ± 0.19-fold (P < 0.05) in SGBS cells induced to adipogenic differentiation in the presence of angiotensin II. Western Blot analysis corroborated reduction of the corresponding proteins to 0.23 ± 0.21 (P < 0.01) and 0.46 ± 0.30-fold (P < 0.01) the respective controls without angiotensin II. Angiotensin II also impaired morphological changes associated with early adipogenesis. Hence, we demonstrated that angiotensin II is able to directly reduce adipogenic differentiation of SGBS preadipose cells.

  5. Novel cellular evidence of lipophagy within the Sertoli cells during spermatogenesis in the turtle

    PubMed Central

    Ahmed, Nisar; Liu, Yi; Chen, Hong; Yang, Ping; Waqas, Yasir; Liu, Tengfei; Gandahi, Jameel Ahmed; Huang, Yufei; Wang, Lingling; Song, Xuejing; Rajput, Imran Rashid; Wang, Taozhi; Chen, Qiusheng

    2017-01-01

    Spermatogenesis is a complex process producing haploid spermatozoa, and the formation of lipid droplets (LDs) within Sertoli cells is critical to maintaining normal spermatogenesis. However, the utilization of LDs within Sertoli cells is still largely unknown. In the present study, proliferation of spermatogonial cells had begun in May, whereas the meiotic cells occurred predominately in July and majority of spermiogenic cells were observed in the seminiferous tubules in October. However, TEM and Oil Red O staining demonstrated that a larger number of LDs had accumulated within the Sertoli cells in May compared to that in October. There were several LDs attached to the isolation membrane/phagophore, suggesting that the LDs may be a source of endogenous energy for the biogenesis of autophagosomes. The LDs were enclosed within the autophagosomes in May, whereas, autophagosomes and mitochondria were directly attached with large LDs within the Sertoli cells in October. Furthermore, immunohistochemistry results demonstrated the stronger localization of LC3 on the Sertoli cells in May than in October. This study is the first to provide clear evidence of the two different modes of lipophagy for lipid consumption within Sertoli cells, which is a key aspect of Sertoli germ cell communication during spermatogenesis. PMID:27750210

  6. Evidence for direct association of Vpr and matrix protein p17 within the HIV-1 virion.

    PubMed

    Sato, A; Yoshimoto, J; Isaka, Y; Miki, S; Suyama, A; Adachi, A; Hayami, M; Fujiwara, T; Yoshie, O

    1996-06-01

    Vpr is one of the auxiliary proteins of HIV-1 and is selectively incorporated into the virion by a process involving the C-terminal p6 portion of the Gag precursor Pr55. Vpr and the matrix protein p17 are the components of the viral preintegration complex and appear to play important roles in the nuclear transport of proviral DNA in nondividing cells. In the present study, we have demonstrated by coimmunoprecipitation experiments that Vpr associates with matrix protein p17 but not with capsid protein p24 within the HIV-1 virion. Experiments employing the yeast two-hybrid GAL4 assay for protein-protein interactions also demonstrated a direct association between Vpr and the C-terminal region of matrix protein p17. Association of Vpr and the matrix protein p17 within the mature virion is consistent with their collaborative role in the nuclear transportation of the viral preintegration complex in nondividing cells such as macrophages.

  7. Scanning probe acoustic microscopy of extruded starch materials: direct visual evidence of starch crystal.

    PubMed

    Liu, Zhongdong; Liu, Boxiang; Li, Mengxing; Wei, Min; Li, Hua; Liu, Peng; Wan, Tuo

    2013-10-15

    Scanning probe acoustic microscopy (SPAM) has been successfully used to study inorganic and keratin biomaterials. However, few studies have attempted to apply SPAM to structural study of non-keratin organic materials such as starch based materials. This study investigated hardness and surface finish to establish sample preparation method suitable for SPAM imaging and acquired clear acoustic images of extruded starch materials. Acquired acoustic images directly exhibited certain structure of starch materials and provided visual evidence of starch material components and aggregates. In addition, through correlating acoustic images with X-ray diffraction data, crystal-structural information in nano-scale was obtained and acoustic image contrast showed a linear relationship with starch amylose content in extruded starch materials.

  8. Evidence for production of single top quarks and first direct measurement of |Vtb|.

    PubMed

    Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahn, S H; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Anderson, S; Andrieu, B; Anzelc, M S; Arnoud, Y; Arov, M; Askew, A; Asman, B; Assis Jesus, A C S; Atramentov, O; Autermann, C; Avila, C; Ay, C; Badaud, F; Baden, A; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, P; Banerjee, S; Barberis, E; Bargassa, P; Baringer, P; Barnes, C; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Berntzon, L; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Binder, M; Biscarat, C; Blackler, I; Blazey, G; Blekman, F; Blessing, S; Bloch, D; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bos, K; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Buchanan, N J; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burke, S; Burnett, T H; Busato, E; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Caron, S; Carvalho, W; Casey, B C K; Cason, N M; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Charles, F; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Claes, D; Clément, B; Clément, C; Coadou, Y; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Cox, B; Crépé-Renaudin, S; Cutts, D; Cwiok, M; da Motta, H; Das, A; Das, M; Davies, B; Davies, G; De, K; de Jong, P; de Jong, S J; De La Cruz-Burelo, E; De Oliveira Martins, C; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Doidge, M; Dominguez, A; Dong, H; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Feligioni, L; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Ford, M; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Gallas, E; Galyaev, E; Garcia, C; Garcia-Bellido, A; Gavrilov, V; Gay, A; Gay, P; Geist, W; Gelé, D; Gelhaus, R; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Hanagaki, K; Hansson, P; Harder, K; Harel, A; Harrington, R; Hauptman, J M; Hauser, R; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinmiller, J M; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hong, S J; Hooper, R; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jenkins, A; Jesik, R; Johns, K; Johnson, C; Johnson, M; Jonckheere, A; Jonsson, P; Juste, A; Käfer, D; Kahn, S; Kajfasz, E; Kalinin, A M; Kalk, J M; Kalk, J R; Kappler, S; Karmanov, D; Kasper, J; Kasper, P; Katsanos, I; Kau, D; Kaur, R; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y M; Khatidze, D; Kim, H; Kim, T J; Kirby, M H; Klima, B; Kohli, J M; Konrath, J-P; Kopal, M; Korablev, V M; Kotcher, J; Kothari, B; Koubarovsky, A; Kozelov, A V; Krop, D; Kryemadhi, A; Kuhl, T; Kumar, A; Kunori, S; Kupco, A; Kurca, T; Kvita, J; Lam, D; Lammers, S; Landsberg, G; Lazoflores, J; Le Bihan, A-C; Lebrun, P; Lee, W M; Leflat, A; Lehner, F; Lesne, V; Leveque, J; Lewis, P; Li, J; Li, L; Li, Q Z; Lietti, S M; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Z; Lobo, L; Lobodenko, A; Lokajicek, M; Lounis, A; Love, P; Lubatti, H J; Lynker, M; Lyon, A L; Maciel, A K A; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Makovec, N; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Mao, H S; Maravin, Y; McCarthy, R; Melnitchouk, A; Mendes, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, A; Meyer, J; Michaut, M; Miettinen, H; Millet, T; Mitrevski, J; Molina, J; Mommsen, R K; Mondal, N K; Monk, J; Moore, R W; Moulik, T; Muanza, G S; Mulders, M; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Noeding, C; Nomerotski, A; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Oguri, V; Oliveira, N; Onoprienko, D; Oshima, N; Osta, J; Otec, R; Otero Y Garzón, G J; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Perea, P M; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Pompos, A; Pope, B G; Popov, A V; Potter, C; Prado da Silva, W L; Prosper, H B; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Rani, K J; Ranjan, K; Ratoff, P N; Renkel, P; Reucroft, S; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Royon, C; Rubinov, P; Ruchti, R; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Santoro, A; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schieferdecker, P; Schmitt, C; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Sengupta, S; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Shpakov, D; Siccardi, V; Sidwell, R A; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smith, R P; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Song, X; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Souza, M; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stone, A; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, M; Ströhmer, R; Strom, D; Strovink, M; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Talby, M; Tamburello, P; Taylor, W; Telford, P; Temple, J; Tiller, B; Titov, M; Tokmenin, V V; Tomoto, M; Toole, T; Torchiani, I; Trefzger, T; Trincaz-Duvoid, S; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; Vachon, B; van den Berg, P J; van Eijk, B; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vartapetian, A; Vasilyev, I A; Vaupel, M; Verdier, P; Vertogradov, L S; Verzocchi, M; Vetterli, M; Villeneuve-Seguier, F; Vint, P; Vlimant, J-R; Von Toerne, E; Voutilainen, M; Vreeswijk, M; Wahl, H D; Wang, L; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Weerts, H; Wermes, N; Wetstein, M; White, A; Wicke, D; Wilson, G W; Wimpenny, S J; Wobisch, M; Womersley, J; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yan, M; Yasuda, T; Yatsunenko, Y A; Yip, K; Yoo, H D; Youn, S W; Yu, C; Yu, J; Yurkewicz, A; Zatserklyaniy, A; Zeitnitz, C; Zhang, D; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zutshi, V; Zverev, E G

    2007-05-04

    The D0 Collaboration presents first evidence for the production of single top quarks at the Fermilab Tevatron pp[over ] collider. Using a 0.9 fb(-1) dataset, we apply a multivariate analysis to separate signal from background and measure sigma(pp[over ]-->tb+X,tqb+X)=4.9+/-1.4 pb. The probability to measure a cross section at this value or higher in the absence of a signal is 0.035%, corresponding to a 3.4 standard deviation significance. We use the cross section measurement to directly determine the Cabibbo-Kobayashi-Maskawa matrix element that describes the Wtb coupling and find 0.68<|V(tb)|

  9. Minimal second language exposure, SES, and early word comprehension: New evidence from a direct assessment.

    PubMed

    Deanda, Stephanie; Arias-Trejo, Natalia; Poulin-Dubois, Diane; Zesiger, Pascal; Friend, Margaret

    2016-01-01

    Although the extant literature provides robust evidence of the influence of language exposure and socioeconomic status (SES) on language acquisition, it is unknown how sensitive the early receptive vocabulary system is to these factors. The current study investigates effects of minimal second language exposure and SES on the comprehension vocabulary of 16-month-old children in the language in which they receive the greatest exposure. Study 1 revealed minimal second language exposure and SES exert significant and independent effects on a direct measure of vocabulary comprehension in English-dominant and English monolingual children (N = 72). In Study 2, we replicated the effect of minimal second language exposure in Spanish-dominant and Spanish monolingual children (N = 86), however no effect of SES on vocabulary was obtained. Our results emphasize the sensitivity of the language system to minimal changes in the environment in early development.

  10. Balancing the 2 Hemispheres in Simple Calculation: Evidence From Direct Cortical Electrostimulation.

    PubMed

    Semenza, C; Salillas, E; De Pallegrin, S; Della Puppa, A

    2016-09-24

    How do the parietal lobes contribute to simple calculation? Clinical and neuroimaging methods, which are based mainly on correlational evidence, have provided contrasting results so far. Here we used direct cortical electrostimulation during brain surgery to causally infer the role of the left and right parietal lobes in simple calculation. Stimulation provoked errors for addition and multiplication in different parietal areas on both hemispheres. Crucially, an innovative qualitative error analysis unveiled the functional contrast of the 2 parietal lobes. Right or left stimulation led to different types of substitution errors in multiplication, unveiling the function of the more active hemisphere. While inhibition of the left hemisphere led mainly to approximation errors, right hemisphere inhibition enhanced retrieval within a stored repertory. These results highlight the respective roles of each hemisphere in the network: rote retrieval of possible solutions by the left parietal areas and approximation to the correct solution by the right hemisphere. The bilateral orchestration between these functions guarantees precise calculation.

  11. Minimal second language exposure, SES, and early word comprehension: New evidence from a direct assessment*

    PubMed Central

    Deanda, Stephanie; Arias-Trejo, Natalia; Poulin-Dubois, Diane; Zesiger, Pascal; Friend, Margaret

    2015-01-01

    Although the extant literature provides robust evidence of the influence of language exposure and socioeconomic status (SES) on language acquisition, it is unknown how sensitive the early receptive vocabulary system is to these factors. The current study investigates effects of minimal second language exposure and SES on the comprehension vocabulary of 16-month-old children in the language in which they receive the greatest exposure. Study 1 revealed minimal second language exposure and SES exert significant and independent effects on a direct measure of vocabulary comprehension in English-dominant and English monolingual children (N = 72). In Study 2, we replicated the effect of minimal second language exposure in Spanish-dominant and Spanish monolingual children (N = 86), however no effect of SES on vocabulary was obtained. Our results emphasize the sensitivity of the language system to minimal changes in the environment in early development. PMID:26957947

  12. Cell-directed-assembly: Directing the formation of nano/bio interfaces and architectures with living cells

    PubMed Central

    Baca, Helen K.; Carnes, Eric C.; Ashley, Carlee E.; Lopez, DeAnna M.; Douthit, Cynthia; Karlin, Shelly; Brinker, C. Jeffrey

    2011-01-01

    Background The desire to immobilize, encapsulate, or entrap viable cells for use in a variety of applications has been explored for decades. Traditionally, the approach is to immobilize cells to utilize a specific functionality of the cell in the system. Scope of Review This review describes our recent discovery that living cells can organize extended nanostructures and nano-objects to create a highly biocompatible nano//bio interface [1]. Major Conclusions We find that short chain phospholipids direct the formation of thin film silica mesophases during evaporation-induced self-assembly (EISA) [2], and that the introduction of cells alter the self-assembly pathway. Cells organize an ordered lipid-membrane that forms a coherent interface with the silica mesophase that is unique in that it withstands drying - yet it maintains accessibility to molecules introduced into the 3D silica host. Cell viability is preserved in the absence of buffer, making these constructs useful as standalone cell-based sensors. In response to hyperosmotic stress, the cells release water, creating a pH gradient which is maintained within the nanostructured host and serves to localize lipids, proteins, plasmids, lipidized nanocrystals, and other components at the cellular surface. This active organization of the bio/nano interface can be accomplished during ink-jet printing or selective wetting - processes allowing patterning of cellular arrays - and even spatially-defined genetic modification. General Significance Recent advances in the understanding of nanotechnology and cell biology encourage the pursuit of more complex endeavors where the dynamic interactions of the cell and host material act symbiotically to obtain new, useful functions. PMID:20933574

  13. Wnt proteins can direct planar cell polarity in vertebrate ectoderm

    PubMed Central

    Chu, Chih-Wen; Sokol, Sergei Y

    2016-01-01

    The coordinated orientation of cells across the tissue plane, known as planar cell polarity (PCP), is manifested by the segregation of core PCP proteins to different sides of the cell. Secreted Wnt ligands are involved in many PCP-dependent processes, yet whether they act as polarity cues has been controversial. We show that in Xenopus early ectoderm, the Prickle3/Vangl2 complex was polarized to anterior cell edges and this polarity was disrupted by several Wnt antagonists. In midgastrula embryos, Wnt5a, Wnt11, and Wnt11b, but not Wnt3a, acted across many cell diameters to orient Prickle3/Vangl2 complexes away from their sources regardless of their positions relative to the body axis. The planar polarity of endogenous Vangl2 in the neuroectoderm was similarly redirected by an ectopic Wnt source and disrupted after depletion of Wnt11b in the presumptive posterior region of the embryo. These observations provide evidence for the instructive role of Wnt ligands in vertebrate PCP. DOI: http://dx.doi.org/10.7554/eLife.16463.001 PMID:27658614

  14. Wnt signalling is a bi-directional vulnerability of cancer cells

    PubMed Central

    Schwarzl, Thomas; Halasz, Melinda; Iljin, Kristiina; Fey, Dirk; Haley, Bridget; Whilde, Jenny; Haapa-Paananen, Saija; Fey, Vidal; Fischer, Matthias; Westermann, Frank; Henrich, Kai-Oliver; Bannert, Steffen; Higgins, Desmond G.; Kolch, Walter

    2016-01-01

    Wnt signalling is involved in the formation, metastasis and relapse of a wide array of cancers. However, there is ongoing debate as to whether activation or inhibition of the pathway holds the most promise as a therapeutic treatment for cancer, with conflicting evidence from a variety of tumour types. We show that Wnt/β-catenin signalling is a bi-directional vulnerability of neuroblastoma, malignant melanoma and colorectal cancer, with hyper-activation or repression of the pathway both representing a promising therapeutic strategy, even within the same cancer type. Hyper-activation directs cancer cells to undergo apoptosis, even in cells oncogenically driven by β-catenin. Wnt inhibition blocks proliferation of cancer cells and promotes neuroblastoma differentiation. Wnt and retinoic acid co-treatments synergise, representing a promising combination treatment for MYCN-amplified neuroblastoma. Additionally, we report novel cross-talks between MYCN and β-catenin signalling, which repress normal β-catenin mediated transcriptional regulation. A β-catenin target gene signature could predict patient outcome, as could the expression level of its DNA binding partners, the TCF/LEFs. This β-catenin signature provides a tool to identify neuroblastoma patients likely to benefit from Wnt-directed therapy. Taken together, we show that Wnt/β-catenin signalling is a bi-directional vulnerability of a number of cancer entities, and potentially a more broadly conserved feature of malignant cells. PMID:27531891

  15. Direct evidence of quantum transport in photosynthetic light-harvesting complexes.

    PubMed

    Panitchayangkoon, Gitt; Voronine, Dmitri V; Abramavicius, Darius; Caram, Justin R; Lewis, Nicholas H C; Mukamel, Shaul; Engel, Gregory S

    2011-12-27

    The photosynthetic light-harvesting apparatus moves energy from absorbed photons to the reaction center with remarkable quantum efficiency. Recently, long-lived quantum coherence has been proposed to influence efficiency and robustness of photosynthetic energy transfer in light-harvesting antennae. The quantum aspect of these dynamics has generated great interest both because of the possibility for efficient long-range energy transfer and because biology is typically considered to operate entirely in the classical regime. Yet, experiments to date show only that coherence persists long enough that it can influence dynamics, but they have not directly shown that coherence does influence energy transfer. Here, we provide experimental evidence that interaction between the bacteriochlorophyll chromophores and the protein environment surrounding them not only prolongs quantum coherence, but also spawns reversible, oscillatory energy transfer among excited states. Using two-dimensional electronic spectroscopy, we observe oscillatory excited-state populations demonstrating that quantum transport of energy occurs in biological systems. The observed population oscillation suggests that these light-harvesting antennae trade energy reversibly between the protein and the chromophores. Resolving design principles evident in this biological antenna could provide inspiration for new solar energy applications.

  16. Direct evidence of quantum transport in photosynthetic light-harvesting complexes

    PubMed Central

    Panitchayangkoon, Gitt; Voronine, Dmitri V.; Abramavicius, Darius; Caram, Justin R.; Lewis, Nicholas H. C.; Mukamel, Shaul; Engel, Gregory S.

    2011-01-01

    The photosynthetic light-harvesting apparatus moves energy from absorbed photons to the reaction center with remarkable quantum efficiency. Recently, long-lived quantum coherence has been proposed to influence efficiency and robustness of photosynthetic energy transfer in light-harvesting antennae. The quantum aspect of these dynamics has generated great interest both because of the possibility for efficient long-range energy transfer and because biology is typically considered to operate entirely in the classical regime. Yet, experiments to date show only that coherence persists long enough that it can influence dynamics, but they have not directly shown that coherence does influence energy transfer. Here, we provide experimental evidence that interaction between the bacteriochlorophyll chromophores and the protein environment surrounding them not only prolongs quantum coherence, but also spawns reversible, oscillatory energy transfer among excited states. Using two-dimensional electronic spectroscopy, we observe oscillatory excited-state populations demonstrating that quantum transport of energy occurs in biological systems. The observed population oscillation suggests that these light-harvesting antennae trade energy reversibly between the protein and the chromophores. Resolving design principles evident in this biological antenna could provide inspiration for new solar energy applications. PMID:22167798

  17. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002

    PubMed Central

    Hong, Yucai; Smischney, Nathan J.; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q.; Honore, Patrick M.; Hofer, Stefan; Caironi, Pietro

    2017-01-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on sepsis, we conducted a systematic review of all randomized controlled EGDT trials. Focus was laid on the setting (emergency department versus ICU) where EGDT was carried out. Early recognition of sepsis, through clinical or automated systems for early alert, together with well-timed initiation of the recommended therapy bundles may improve patients’ outcome. However, the original “EGDT” protocol by Rivers and coworkers has been largely modified in subsequent trials. Currently, many investigators opt for an “expanded” EGDT (as suggested by the Surviving Sepsis Campaign). Evidence is also presented on the effectiveness of automated systems for early sepsis alert. Early recognition of sepsis and well-timed initiation of the SSC bundle may improve patient outcome. PMID:28275488

  18. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002.

    PubMed

    Zhang, Zhongheng; Hong, Yucai; Smischney, Nathan J; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q; Honore, Patrick M; Hofer, Stefan; Caironi, Pietro

    2017-02-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on sepsis, we conducted a systematic review of all randomized controlled EGDT trials. Focus was laid on the setting (emergency department versus ICU) where EGDT was carried out. Early recognition of sepsis, through clinical or automated systems for early alert, together with well-timed initiation of the recommended therapy bundles may improve patients' outcome. However, the original "EGDT" protocol by Rivers and coworkers has been largely modified in subsequent trials. Currently, many investigators opt for an "expanded" EGDT (as suggested by the Surviving Sepsis Campaign). Evidence is also presented on the effectiveness of automated systems for early sepsis alert. Early recognition of sepsis and well-timed initiation of the SSC bundle may improve patient outcome.

  19. Porous silicon-based direct hydrogen sulphide fuel cells.

    PubMed

    Dzhafarov, T D; Yuksel, S Aydin

    2011-10-01

    In this paper, the use of Au/porous silicon/Silicon Schottky type structure, as a direct hydrogen sulphide fuel cell is demonstrated. The porous silicon filled with hydrochlorid acid was developed as a proton conduction membrane. The Au/Porous Silicon/Silicon cells were fabricated by first creating the porous silicon layer in single-crystalline Si using the anodic etching under illumination and then deposition Au catalyst layer onto the porous silicon. Using 80 mM H2S solution as fuel the open circuit voltage of 0.4 V was obtained and maximum power density of 30 W/m2 at room temperature was achieved. These results demonstrate that the Au/Porous Silicon/Silicon direct hydrogen sulphide fuel cell which uses H2S:dH2O solution as fuel and operates at room temperature can be considered as the most promising type of low cost fuel cell for small power-supply units.

  20. Direct carbonate fuel cell power plant operating with logistic fuels

    SciTech Connect

    Abens, S.G.; Steinfeld, G.

    1997-12-31

    In response to the US Department of Defense need for power generators which operate with logistic fuels, Energy Research Corporation and its subcontractors, Haldor Topsoe and Fluor Daniel, have conducted design studies and subscale equipment tests toward the development of fuel cell power plants with multifuel capability. A principal objective of this work was the development of a fixed-base carbonate fuel cell power plant design which can utilize both natural gas and military logistic fuels DF-2 and JP-8. To verify ERC`s technical approach, a 32 kW brassboard logistic fuel preprocessing system was assembled and operated with a Direct Carbonate Fuel Cell (DFC) stack. The project was conducted as part of DARPA`s Fuel Cell Power Plant Initiative Program for the development of dual use fuel cell power plants. The logistic fuel preprocessor consisted of a hydrodesulfurization plant which supplied desulfurized feed to an adiabatic prereformer. The methane-rich product gas provides fuel cell performance similar to that with natural gas. A preliminary design of a 3MW multifuel power plant prepared with input from the 32kW brassboard test confirmed that the thermal efficiency of a DFC power plant is nearly as high with logistic fuel (57%) as it is with natural gas (58%).

  1. Direct chromosome-length haplotyping by single-cell sequencing.

    PubMed

    Porubský, David; Sanders, Ashley D; van Wietmarschen, Niek; Falconer, Ester; Hills, Mark; Spierings, Diana C J; Bevova, Marianna R; Guryev, Victor; Lansdorp, Peter M

    2016-11-01

    Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods to directly chart the unique genetic makeup of each parental chromosome are lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach to phasing diploid genomes along the entire length of all chromosomes. We demonstrate this by building a complete haplotype for a HapMap individual (NA12878) at high accuracy (concordance 99.3%), without using generational information or statistical inference. By use of this approach, we mapped all meiotic recombination events in a family trio with high resolution (median range ∼14 kb) and phased larger structural variants like deletions, indels, and balanced rearrangements like inversions. Lastly, the single-cell resolution of Strand-seq allowed us to observe loss of heterozygosity regions in a small number of cells, a significant advantage for studies of heterogeneous cell populations, such as cancer cells. We conclude that Strand-seq is a unique and powerful approach to completely phase individual genomes and map inheritance patterns in families, while preserving haplotype differences between single cells.

  2. Direct Observation of Nanoparticle-Cancer Cell Nucleus Interactions

    PubMed Central

    Dam, Duncan Hieu M.; Lee, Jung Heon; Sisco, Patrick N.; Co, Dick T.; Zhang, Ming; Wasielewski, Michael R.; Odom, Teri W.

    2012-01-01

    We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultra-fast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy. PMID:22424173

  3. Liquid Tin Anode Direct Coal Fuel Cell Final Program Report

    SciTech Connect

    Tao, Thomas

    2012-01-26

    This SBIR program will result in improved LTA cell technology which is the fundamental building block of the Direct Coal ECL concept. As described below, ECL can make enormous efficiency and cost contributions to utility scale coal power. This program will improve LTA cells for small scale power generation. As described in the Commercialization section, there are important intermediate military and commercial markets for LTA generators that will provide an important bridge to the coal power application. The specific technical information from this program relating to YSZ electrolyte durability will be broadly applicable SOFC developers working on coal based SOFC generally. This is an area about which very little is currently known and will be critical for successfully applying fuel cells to coal power generation.

  4. Catalytic polymeric electrodes for direct borohydride fuel cells

    NASA Astrophysics Data System (ADS)

    Bayatsarmadi, Bita; Peters, Alice; Talemi, Pejman

    2016-08-01

    The direct borohydride fuel cell (DBFC) is a new class of fuel cells that produces non-toxic by-products and has a potential for a high voltage and high energy density. A major challenge in developing efficient DBFCs is the development of an efficient, stable, and economic catalyst for the oxidation of borohydride. In this paper, we report the use of conducting polymer Poly(3,4-ethylenedioxythiophene) (PEDOT) as electrocatalysts in DBFC. PEDOT electrodes prepared by vacuum phase polymerization exhibited electrocatalytic behavior towards oxidation of borohydride and reduction of hydrogen peroxide. Spectroscopic analysis of samples showed that PEDOT can act as an interface for electron transfer from borohydride ions. Comparing the polarization curves of DBFCs with PEDOT coated on graphite electrodes and cells with bare graphite electrodes, demonstrated higher voltage, maximum power density, and stability.

  5. Low contaminant formic acid fuel for direct liquid fuel cell

    DOEpatents

    Masel, Richard I.; Zhu, Yimin; Kahn, Zakia; Man, Malcolm

    2009-11-17

    A low contaminant formic acid fuel is especially suited toward use in a direct organic liquid fuel cell. A fuel of the invention provides high power output that is maintained for a substantial time and the fuel is substantially non-flammable. Specific contaminants and contaminant levels have been identified as being deleterious to the performance of a formic acid fuel in a fuel cell, and embodiments of the invention provide low contaminant fuels that have improved performance compared to known commercial bulk grade and commercial purified grade formic acid fuels. Preferred embodiment fuels (and fuel cells containing such fuels) including low levels of a combination of key contaminants, including acetic acid, methyl formate, and methanol.

  6. Direct observation of nanoparticle-cancer cell nucleus interactions.

    PubMed

    Dam, Duncan Hieu M; Lee, Jung Heon; Sisco, Patrick N; Co, Dick T; Zhang, Ming; Wasielewski, Michael R; Odom, Teri W

    2012-04-24

    We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.

  7. Immunotherapy for small-cell lung cancer: emerging evidence.

    PubMed

    Reck, Martin; Heigener, David; Reinmuth, Niels

    2016-04-01

    Treatment for small-cell lung cancer (SCLC) has changed little over the past few decades; available therapies have failed to extend survival in advanced disease. In recent years, immunotherapy with treatments such as interferons, TNFs, vaccines and immune checkpoint inhibitors has advanced and shown promise in the treatment of several tumor types. Immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab, durvalumab, tremelimumab and ulocuplumab are at the forefront of immunotherapy and have achieved approvals for certain cancer types, including melanoma (ipilimumab, nivolumab and pembrolizumab), non-SCLC (nivolumab and pembrolizumab) and renal cell carcinoma (nivolumab). Clinical trials are investigating different immunotherapies in patients with other solid and hematologic malignancies, including SCLC. We review emerging evidence supporting the use of immunotherapy in SCLC patients.

  8. Direct evidence of lipid rafts by in situ atomic force microscopy.

    PubMed

    Cai, Mingjun; Zhao, Weidong; Shang, Xin; Jiang, Junguang; Ji, Hongbin; Tang, Zhiyong; Wang, Hongda

    2012-04-23

    Lipid rafts are membrane microdomains enriched with cholesterol, glycosphingolipids, and proteins. Although they are broadly presumed to play a pivotal role in various cellular functions, there are still fierce debates about the composition, functions, and even existence of lipid rafts. Here high-resolution and time-lapse in situ atomic force microscopy is used to directly confirm the existence of lipid rafts in native erythrocyte membranes. The results indicate some important aspects of lipid rafts: most of the lipid rafts are in the size range of 100-300 nm and have irregular shape; the detergent-resistant membranes consist of cholesterol microdomains and are not likely the same as the lipid rafts; cholesterol contributes significantly to the formation and stability of the protein domains; and Band III is an important protein of lipid rafts in the inner leaflet of erythrocyte membranes, indicating that lipid rafts are exactly the functional domains in plasma membrane. This work provides direct evidence of the presence, size, and main constitutive protein of lipid rafts at a resolution of a few nanometers, which will pave the way for studying their structure and functions in detail.

  9. No evidence for directional evolution of body mass in herbivorous theropod dinosaurs.

    PubMed

    Zanno, Lindsay E; Makovicky, Peter J

    2013-01-22

    The correlation between large body size and digestive efficiency has been hypothesized to have driven trends of increasing mass in herbivorous clades by means of directional selection. Yet, to date, few studies have investigated this relationship from a phylogenetic perspective, and none, to our knowledge, with regard to trophic shifts. Here, we reconstruct body mass in the three major subclades of non-avian theropod dinosaurs whose ecomorphology is correlated with extrinsic evidence of at least facultative herbivory in the fossil record--all of which also achieve relative gigantism (more than 3000 kg). Ordinary least-squares regressions on natural log-transformed mean mass recover significant correlations between increasing mass and geological time. However, tests for directional evolution in body mass find no support for a phylogenetic trend, instead favouring passive models of trait evolution. Cross-correlation of sympatric taxa from five localities in Asia reveals that environmental influences such as differential habitat sampling and/or taphonomic filtering affect the preserved record of dinosaurian body mass in the Cretaceous. Our results are congruent with studies documenting that behavioural and/or ecological factors may mitigate the benefit of increasing mass in extant taxa, and suggest that the hypothesis can be extrapolated to herbivorous lineages across geological time scales.

  10. No evidence for directional evolution of body mass in herbivorous theropod dinosaurs

    PubMed Central

    Zanno, Lindsay E.; Makovicky, Peter J.

    2013-01-01

    The correlation between large body size and digestive efficiency has been hypothesized to have driven trends of increasing mass in herbivorous clades by means of directional selection. Yet, to date, few studies have investigated this relationship from a phylogenetic perspective, and none, to our knowledge, with regard to trophic shifts. Here, we reconstruct body mass in the three major subclades of non-avian theropod dinosaurs whose ecomorphology is correlated with extrinsic evidence of at least facultative herbivory in the fossil record—all of which also achieve relative gigantism (more than 3000 kg). Ordinary least-squares regressions on natural log-transformed mean mass recover significant correlations between increasing mass and geological time. However, tests for directional evolution in body mass find no support for a phylogenetic trend, instead favouring passive models of trait evolution. Cross-correlation of sympatric taxa from five localities in Asia reveals that environmental influences such as differential habitat sampling and/or taphonomic filtering affect the preserved record of dinosaurian body mass in the Cretaceous. Our results are congruent with studies documenting that behavioural and/or ecological factors may mitigate the benefit of increasing mass in extant taxa, and suggest that the hypothesis can be extrapolated to herbivorous lineages across geological time scales. PMID:23193135

  11. Direct Evidence of the Transition from Weak to Strong Magnetohydrodynamic Turbulence

    NASA Astrophysics Data System (ADS)

    Meyrand, Romain; Galtier, Sébastien; Kiyani, Khurom H.

    2016-03-01

    One of the most important predictions in magnetohydrodynamics is that in the presence of a uniform magnetic field b0e^∥ a transition from weak to strong wave turbulence should occur when going from large to small perpendicular scales. This transition is believed to be a universal property of several anisotropic turbulent systems. We present, for the first time, direct evidence of such a transition using a decaying three-dimensional direct numerical simulation of incompressible balanced magnetohydrodynamic turbulence with a grid resolution of 30722×256 . From large to small scales, the change of regime is characterized by (i) a change of slope in the energy spectrum going from approximately -2 to -3 /2 , (ii) an increase of the ratio between the wave and nonlinear times, with a critical ratio of χc˜1 /3 , (iii) a modification of the isocontours of energy revealing a transition from a purely perpendicular cascade to a cascade compatible with the critical-balance-type phenomenology, and (iv) an absence followed by a dramatic increase of the communication between Alfvén modes. The changes happen at approximately the same transition scale and can be seen as manifest signatures of the transition from weak to strong wave turbulence. Furthermore, we observe a significant nonlocal three-wave coupling between strongly and weakly nonlinear modes resulting in an inverse transfer of energy from small to large scales.

  12. Direct evidence for impact winter following the Cretaceous-Paleogene bolide impact

    NASA Astrophysics Data System (ADS)

    Vellekoop, J.; Sluijs, A.; Smit, J.; Schouten, S.; Sinninghe Damsté, J. S.; Brinkhuis, H.

    2012-12-01

    The Cretaceous/Paleogene (K/Pg) boundary, ~65.5 Ma, marks a mass-extinction event related the impact of a large asteroid on the Yucatan peninsula, Mexico. Model scenarios predict that the explosive injection of dust and sulfate aerosols into the stratosphere blocked incoming solar radiation, resulting in a cooling pulse of months to several decades, a so-called 'impact winter', but thus far, proxy records lack sufficient resolution to evaluate this hypothesis. We report on a major, short-lived drop in sea surface temperatures (SSTs) recorded in an unusually well preserved and stratigraphically expanded K/Pg boundary site in Texas, USA, based on TEX86 paleothermometry. Critically, the cooling directly post-dates impact-related tsunami deposits, and coincides with the deposition of extraterrestrial iridium representing aerosol fall out, restricting the age of the cooling to the first months to decades after impact. We interpret this cooling to reflect the first direct evidence for the "impact winter" at the K/Pg boundary. The combination of darkness and cooling must have been a key contributory element in the extinctions of many biological clades, including the dinosaurs, flying reptiles and marine reptiles.

  13. Direct evidence for distance measurement via flexible stride integration in the fiddler crab.

    PubMed

    Walls, Michael L; Layne, John E

    2009-01-13

    While on foraging excursions, fiddler crabs track their burrow location despite having no visual contact with it . They do this by path integration, a common navigational process in which motion vectors (the direction and distance of animals' movements) are summed to form a single "home vector" linking the current location with the point of origin. Here, we identify the mechanism by which the integrator measures distance, by decoupling motor output from both inertial and visual feedback. Fiddler crabs were passively translated to a position such that the home vector lay across an acetate sheet on the ground. After being frightened, crabs tried to escape but slipped as they did so. Detailed high-speed video analysis reveals that crabs measure distance by integrating strides, rather than linear acceleration or optic flow: the number of steps they took depended on both the length of the home vector and how large their steps were, whether they slipped and fell short or not. This is the most direct evidence to date of a stride integrator that is flexible enough to account for significant variation in stride length and frequency.

  14. Evidence of direct complementary interactions between messenger RNAs and their cognate proteins

    PubMed Central

    Polyansky, Anton A.; Zagrovic, Bojan

    2013-01-01

    Recently, the ability to interact with messenger RNA (mRNA) has been reported for a number of known RNA-binding proteins, but surprisingly also for different proteins without recognizable RNA binding domains including several transcription factors and metabolic enzymes. Moreover, direct binding to cognate mRNAs has been detected for multiple proteins, thus creating a strong impetus to search for functional significance and basic physico-chemical principles behind such interactions. Here, we derive interaction preferences between amino acids and RNA bases by analyzing binding interfaces in the known 3D structures of protein–RNA complexes. By applying this tool to human proteome, we reveal statistically significant matching between the composition of mRNA sequences and base-binding preferences of protein sequences they code for. For example, purine density profiles of mRNA sequences mirror guanine affinity profiles of cognate protein sequences with quantitative accuracy (median Pearson correlation coefficient R = −0.80 across the entire human proteome). Notably, statistically significant anti-matching is seen only in the case of adenine. Our results provide strong evidence for the stereo-chemical foundation of the genetic code and suggest that mRNAs and cognate proteins may in general be directly complementary to each other and associate, especially if unstructured. PMID:23868089

  15. Direct evidence of strong local ferroelectric ordering in a thermoelectric semiconductor

    SciTech Connect

    Aggarwal, Leena; Sekhon, Jagmeet S.; Arora, Ashima; Sheet, Goutam; Guin, Satya N.; Negi, Devendra S.; Datta, Ranjan; Biswas, Kanishka

    2014-09-15

    It is thought that the proposed new family of multi-functional materials, namely, the ferroelectric thermoelectrics may exhibit enhanced functionalities due to the coupling of the thermoelectric parameters with ferroelectric polarization in solids. Therefore, the ferroelectric thermoelectrics are expected to be of immense technological and fundamental significance. As a first step towards this direction, it is most important to identify the existing high performance thermoelectric materials exhibiting ferroelectricity. Herein, through the direct measurement of local polarization switching, we show that the recently discovered thermoelectric semiconductor AgSbSe{sub 2} has local ferroelectric ordering. Using piezo-response force microscopy, we demonstrate the existence of nanometer scale ferroelectric domains that can be switched by external electric field. These observations are intriguing as AgSbSe{sub 2} crystalizes in cubic rock-salt structure with centro-symmetric space group (Fm–3m), and therefore, no ferroelectricity is expected. However, from high resolution transmission electron microscopy measurement, we found the evidence of local superstructure formation which, we believe, leads to local distortion of the centro-symmetric arrangement in AgSbSe{sub 2} and gives rise to the observed ferroelectricity. Stereochemically active 5S{sup 2} lone-pair of Sb may also give rise to local structural distortion thereby creating ferroelectricity in AgSbSe{sub 2}.

  16. Engineered microtopographies and surface chemistries direct cell attachment and function

    NASA Astrophysics Data System (ADS)

    Magin, Chelsea Marie

    topographically modified surface (R2=0.82). Functionalized PEGDMA hydrogels significantly reduced attachment and attachment strength of Navicula and C. marina. These hydrogels also reduced attachment of zoospores of Ulva compared to PDMSe. Attachment of Ulva to microtopographies in PDMSe and PEGDMA-co-HEMA negatively correlated with ERIII*Re (R2 = 0.94 and R2 = 0.99, respectively). Incorporating a surface energy term into this equation created a correlation between the attachment densities of cells from two evolutionarily diverse groups on substrates of two surface chemistries with an equation that describes the various microtopographies and surface chemistries in terms of surface energy (R2 = 0.80). The current Attachment Model can now be used to design engineered antifouling surface microtopographies and chemistries that inhibit the attachment of organisms from three evoluntionarily diverse groups. Hydrogels based on PEGDMA were also chosen as a substratum material for mammalian cell culture. Capturing endothelial progenitor cells (EPCs) and inducing differentiation into the endothelial cell (EC) phenotype is the ideal way to re-endothelialize a small-diameter vascular graft. Substratum elasticity has been reported to direct stem cell differentiation into specific lineages. Functionalized PEGDMA hydrogels provided good compliance, high fidelity of topographic features and sites for surface modification with biomolecules. Fibronectin grafting and topography both increased EC attachment. This combination of adjustable elasticity, surface chemistry and topography has the potential to promote the capture and differentiation of EPCs into a confluent EC monolayer. Engineered microtopographies replicated in PDMSe directed elongation and alignment of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs) compared to smooth surfaces. Engineered cellular micro-environments were created with specific surface energies defined by chemistry

  17. RNA Directed Modulation of Phenotypic Plasticity in Human Cells

    PubMed Central

    Burdach, Jon; Morris, Kevin V.

    2016-01-01

    Natural selective processes have been known to drive phenotypic plasticity, which is the emergence of different phenotypes from one genome following environmental stimulation. Long non-coding RNAs (lncRNAs) have been observed to modulate transcriptional and epigenetic states of genes in human cells. We surmised that lncRNAs are governors of phenotypic plasticity and drive natural selective processes through epigenetic modulation of gene expression. Using heat shocked human cells as a model we find several differentially expressed transcripts with the top candidates being lncRNAs derived from retro-elements. One particular retro-element derived transcripts, Retro-EIF2S2, was found to be abundantly over-expressed in heat shocked cells. Over-expression of Retro-EIF2S2 significantly enhanced cell viability and modulated a predisposition for an adherent cellular phenotype upon heat shock. Mechanistically, we find that this retro-element derived transcript interacts directly with a network of proteins including 40S ribosomal protein S30 (FAU), Eukaryotic translation initiation factor 5A (EIF5A), and Ubiquitin-60S ribosomal protein L40 (UBA52) to affect protein modulated cell adhesion pathways. We find one motif in Retro-EIF2S2 that exhibits binding to FAU and modulates phenotypic cell transitions from adherent to suspension states. The observations presented here suggest that retroviral derived transcripts actively modulate phenotypic plasticity in human cells in response to environmental selective pressures and suggest that natural selection may play out through the action of retro-elements in human cells. PMID:27082860

  18. RNA Directed Modulation of Phenotypic Plasticity in Human Cells.

    PubMed

    Trakman, Laura; Hewson, Chris; Burdach, Jon; Morris, Kevin V

    2016-01-01

    Natural selective processes have been known to drive phenotypic plasticity, which is the emergence of different phenotypes from one genome following environmental stimulation. Long non-coding RNAs (lncRNAs) have been observed to modulate transcriptional and epigenetic states of genes in human cells. We surmised that lncRNAs are governors of phenotypic plasticity and drive natural selective processes through epigenetic modulation of gene expression. Using heat shocked human cells as a model we find several differentially expressed transcripts with the top candidates being lncRNAs derived from retro-elements. One particular retro-element derived transcripts, Retro-EIF2S2, was found to be abundantly over-expressed in heat shocked cells. Over-expression of Retro-EIF2S2 significantly enhanced cell viability and modulated a predisposition for an adherent cellular phenotype upon heat shock. Mechanistically, we find that this retro-element derived transcript interacts directly with a network of proteins including 40S ribosomal protein S30 (FAU), Eukaryotic translation initiation factor 5A (EIF5A), and Ubiquitin-60S ribosomal protein L40 (UBA52) to affect protein modulated cell adhesion pathways. We find one motif in Retro-EIF2S2 that exhibits binding to FAU and modulates phenotypic cell transitions from adherent to suspension states. The observations presented here suggest that retroviral derived transcripts actively modulate phenotypic plasticity in human cells in response to environmental selective pressures and suggest that natural selection may play out through the action of retro-elements in human cells.

  19. Differential response of glioma cells to FOXO1-directed therapy.

    PubMed

    Lau, Cara J; Koty, Zaf; Nalbantoglu, Josephine

    2009-07-01

    Gliomas are the most common adult primary brain tumors, and the most malignant form, glioblastoma multiforme, is invariably fatal. The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is altered in most glioblastoma multiforme. PTEN, an important negative regulator of the PI3K-Akt pathway, is also commonly mutated in glioma, leading to constitutive activation of Akt. One ultimate consequence is phosphorylation and inactivation of FOXO forkhead transcription factors that regulate genes involved in apoptosis, cell cycle arrest, nutrient availability, DNA repair, stress, and angiogenesis. We tested the ability of a mutant FOXO1 factor that is not subject to Akt phosphorylation to overcome dysregulated PI3K-Akt signaling in two PTEN-null glioma cell lines, U87 and U251. Adenovirus-mediated gene transfer of the mutant FOXO1 successfully restored cell cycle arrest and induced cell death in vitro and prolonged survival in vivo in xenograft models of human glioma (33% survival at 1 year of animals bearing U251 tumors). However, U87 were much more resistant than U251 to mutant FOXO1-induced death, showing evidence of increased nuclear export and Akt-independent phosphorylation of FOXO1 at S249. A cyclin-dependent kinase 2 inhibitor decreased phosphorylation of S249 and rendered U87 cells significantly more susceptible to mutant FOXO1-induced death. Our results indicate that targeting FOXO1, which is at the convergence point of several growth factor receptor tyrosine kinase pathways, can effectively induce glioma cell death and inhibit tumor growth. They also highlight the importance of Akt-independent phosphorylation events in the nuclear export of FOXO1.

  20. Efficient direct ZnO/CIS solar cells

    SciTech Connect

    Olsen, L.C.; William Addis, F.; Lei, W.; Li, J.

    1996-01-01

    This paper describes investigations of CIS solar cells with ZnO window layers deposited by MOCVD. These studies have been conducted with graded absorber CIS substrates obtained from Siemens Solar. Cell fabrication involves surface preparation of the Siemens substrate, growth of 200 to 400 A of undoped ZnO by MOCVD, deposition of a highly conducting ZnO top contact layer and deposition of a Ni/Ag collector grid. MOCVD growth of ZnO is accomplished in a SPIRE 500XT reactor by reacting a zinc adduct and tetrahydrofuran. Processing development has been conducted by forming test cells on ZnO/CIS structures by depositing thin, transparent Al contacts 2.8 mm in diameter on top of the ZnO window layer to serve as contacts. Several cells have been completed with a total area efficiency {ge}11.0{percent}, with the best result being 11.3{percent}. The best active area efficiency is approximately 12{percent}. Other topics discussed include current-voltage characteristics of direct ZnO/CIS cells. {copyright} {ital 1996 American Institute of Physics.}

  1. Low Crossover Polymer Electrolyte Membranes for Direct Methanol Fuel Cells

    NASA Technical Reports Server (NTRS)

    Prakash, G. K. Surya; Smart, Marshall; Atti, Anthony R.; Olah, George A.; Narayanan, S. R.; Valdez, T.; Surampudi, S.

    1996-01-01

    Direct Methanol Fuel Cells (DMFC's) using polymer electrolyte membranes are promising power sources for portable and vehicular applications. State of the art technology using Nafion(R) 117 membranes (Dupont) are limited by high methanol permeability and cost, resulting in reduced fuel cell efficiencies and impractical commercialization. Therefore, much research in the fuel cell field is focused on the preparation and testing of low crossover and cost efficient polymer electrolyte membranes. The University of Southern California in cooperation with the Jet Propulsion Laboratory is focused on development of such materials. Interpenetrating polymer networks are an effective method used to blend polymer systems without forming chemical links. They provide the ability to modify physical and chemical properties of polymers by optimizing blend compositions. We have developed a novel interpenetrating polymer network based on poly (vinyl - difluoride)/cross-linked polystyrenesulfonic acid polymer composites (PVDF PSSA). Sulfonation of polystyrene accounts for protonic conductivity while the non-polar, PVDF backbone provides structural integrity in addition to methanol rejection. Precursor materials were prepared and analyzed to characterize membrane crystallinity, stability and degree of interpenetration. USC JPL PVDF-PSSA membranes were also characterized to determine methanol permeability, protonic conductivity and sulfur distribution. Membranes were fabricated into membrane electrode assemblies (MEA) and tested for single cell performance. Tests include cell performance over a wide range of temperatures (20 C - 90 C) and cathode conditions (ambient Air/O2). Methanol crossover values are measured in situ using an in-line CO2 analyzer.

  2. Direct borohydride fuel cell using Ni-based composite anodes

    NASA Astrophysics Data System (ADS)

    Ma, Jia; Sahai, Yogeshwar; Buchheit, Rudolph G.

    In this study, nickel-based composite anode catalysts consisting of Ni with either Pd on carbon or Pt on carbon (the ratio of Ni:Pd or Ni:Pt being 25:1) were prepared for use in direct borohydride fuel cells (DBFCs). Cathode catalysts used were 1 mg cm -2 Pt/C or Pd electrodeposited on activated carbon cloth. The oxidants were oxygen, oxygen in air, or acidified hydrogen peroxide. Alkaline solution of sodium borohydride was used as fuel in the cell. High power performance has been achieved by DBFC using non-precious metal, Ni-based composite anodes with relatively low anodic loading (e.g., 270 mW cm -2 for NaBH 4/O 2 fuel cell at 60 °C, 665 mW cm -2 for NaBH 4/H 2O 2 fuel cell at 60 °C). Effects of temperature, oxidant, and anode catalyst loading on the DBFC performance were investigated. The cell was operated for about 100 h and its performance stability was recorded.

  3. Deterministic direct reprogramming of somatic cells to pluripotency.

    PubMed

    Rais, Yoach; Zviran, Asaf; Geula, Shay; Gafni, Ohad; Chomsky, Elad; Viukov, Sergey; Mansour, Abed AlFatah; Caspi, Inbal; Krupalnik, Vladislav; Zerbib, Mirie; Maza, Itay; Mor, Nofar; Baran, Dror; Weinberger, Leehee; Jaitin, Diego A; Lara-Astiaso, David; Blecher-Gonen, Ronnie; Shipony, Zohar; Mukamel, Zohar; Hagai, Tzachi; Gilad, Shlomit; Amann-Zalcenstein, Daniela; Tanay, Amos; Amit, Ido; Novershtern, Noa; Hanna, Jacob H

    2013-10-03

    Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem (iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.

  4. The differentiation directions of the bone marrow stromal cells under modeling microgravity

    NASA Astrophysics Data System (ADS)

    Nesterenko, Olga; Rodionova, Natalia; Katkova, Olena

    Within experiments on rats simulating microgravity by base load remove from back limbs (duration of the experiment 1,5 months) on marrow stromal cells cultures (ex vivo, in vitro) comprising osteogenic cells-predecessors, extracted from femurs, studied their peculiarities of the colony formation ablity, the cell structure, some cytological and ultra-structural characteristics and differentiation direction. It was found that that under microgravity conditions there is a decline of the stromal cells colony formation intensity, decrease of the colonies size and cells mitotic activity that indicates decrease of their growth potential. Both in control and in experiment the colonies were presented by population of low-differentiated cells, differentiated cells and mature cells. The comparative cytological and morphometric analysis have shown that the studied stromal cells in colonies have the smaller sizes, more elongated shape, and higher nucleocytoplasmic ratio. Cells composition in the experiment colonies is reliably different by the ratio of the low-differentiating to being differentiated cells; a ratio of low-differentiated to already differentiated cells; ratio of differentiated cells to total number of all cells. In comparison with control group, amount of the cells passed trough a differentiation stage and mature cells in colonies is decreased by 3 to 4 times. Among the differentiated stromal cells in colonies increasing amount of adipocytes was revealed. The analysis of electron microscope microphotographs showed that in osteogenic cells differentiated under microgravity conditions, there is a reduction of the specific volume of a granular endoplasmic reticulum, Golgi's complex and quantity of nuclei reduction that indicates depression of the specific biosyntheses process intensity in cells. The increase of lysosomes and myelinic structures quantity is linked to organelles partial reduction. Consolidation of mitochondrias is an evidence of the cells’ energy

  5. Manipulation of neutrophil-like HL-60 cells for the study of directed cell migration.

    PubMed

    Millius, Arthur; Weiner, Orion D

    2010-01-01

    Many cells undergo directed cell migration in response to external cues in a process known as chemotaxis. This ability is essential for many single-celled organisms to hunt and mate, the development of multicellular organisms, and the functioning of the immune system. Because of their relative ease of manipulation and their robust chemotactic abilities, the neutrophil-like cell line (HL-60) has been a powerful system to analyze directed cell migration. In this chapter, we describe the maintenance and transient transfection of HL-60 cells and explain how to analyze their behavior with two standard chemotactic assays (micropipette and EZ-TAXIS). Finally, we demonstrate how to fix and stain the actin cytoskeleton of polarized cells for fluorescent microscopy imaging.

  6. Left-right asymmetric cell intercalation drives directional collective cell movement in epithelial morphogenesis

    NASA Astrophysics Data System (ADS)

    Sato, Katsuhiko; Hiraiwa, Tetsuya; Maekawa, Emi; Isomura, Ayako; Shibata, Tatsuo; Kuranaga, Erina

    2015-12-01

    Morphogenetic epithelial movement occurs during embryogenesis and drives complex tissue formation. However, how epithelial cells coordinate their unidirectional movement while maintaining epithelial integrity is unclear. Here we propose a novel mechanism for collective epithelial cell movement based on Drosophila genitalia rotation, in which epithelial tissue rotates clockwise around the genitalia. We found that this cell movement occurs autonomously and requires myosin II. The moving cells exhibit repeated left-right-biased junction remodelling, while maintaining adhesion with their neighbours, in association with a polarized myosin II distribution. Reducing myosinID, known to cause counter-clockwise epithelial-tissue movement, reverses the myosin II distribution. Numerical simulations revealed that a left-right asymmetry in cell intercalation is sufficient to induce unidirectional cellular movement. The cellular movement direction is also associated with planar cell-shape chirality. These findings support a model in which left-right asymmetric cell intercalation within an epithelial sheet drives collective cellular movement in the same direction.

  7. A novel membrane-less direct alcohol fuel cell

    NASA Astrophysics Data System (ADS)

    Yi, Qingfeng; Chen, Qinghua; Yang, Zheng

    2015-12-01

    Membrane-less fuel cell possesses such advantages as simplified design and lower cost. In this paper, a membrane-less direct alcohol fuel cell is constructed by using multi-walled carbon nanotubes (MWCNT) supported Pd and ternary PdSnNi composites as the anode catalysts and Fe/C-PANI composite, produced by direct pyrolysis of Fe-doped polyaniline precursor, as the oxygen reduction reaction (ORR) catalyst. The alcohols investigated in the present study are methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol and sec-butanol. The cathode catalyst Fe/C-PANI is electrochemically inactive to oxidation of the alcohols. The performance of the cell with various alcohols in 1 mol L-1 NaOH solution on either Pd/MWCNT or PdSnNi/MWCNT catalyst has been evaluated. In any case, the performance of the cell using the anode catalyst PdSnNi/MWCNT is considerably better than Pd/MWCNT. For the PdSnNi/MWCNT, the maximum power densities of the cell using methanol (0.5 mol L-1), ethanol (0.5 mol L-1), n-propanol (0.5 mol L-1), iso-propanol (0.5 mol L-1), n-butanol (0.2 mol L-1), iso-butanol (0.2 mol L-1) and sec-butanol (0.2 mol L-1) are 0.34, 1.03, 1.07, 0.44, 0.50, 0.31 and 0.15 mW cm-2, respectively.

  8. Direct Methanol Fuel Cell Prototype Demonstration for Consumer Electronics Applications

    SciTech Connect

    Carlstrom, Charles, M., Jr.

    2009-07-07

    This report is the final technical report for DOE Program DE-FC36-04GO14301 titled “Direct Methanol Fuel Cell Prototype Demonstration for Consumer Electronics Applications”. Due to the public nature of this report some of the content reported in confidential reports and meetings to the DOE is not covered in detail in this report and some of the content has been normalized to not show actual values. There is a comparison of the projects accomplishments with the objectives, an overview of some of the key subsystem work, and a review of the three levels of prototypes demonstrated during the program. There is also a description of the eventual commercial product and market this work is leading towards. The work completed under this program has significantly increased the understanding of how Direct Methanol Fuel Cells (DMFC) can be deployed successfully to power consumer electronic devices. The prototype testing has demonstrated the benefits a direct methanol fuel cell system has over batteries typically used for powering consumer electronic devices. Three generations of prototypes have been developed and tested for performance, robustness and life. The technologies researched and utilized in the fuel cell stack and related subsystems for these prototypes are leveraged from advances in other industries such as the hydrogen fueled PEM fuel cell industry. The work under this program advanced the state of the art of direct methanol fuel cells. The system developed by MTI micro fuel cells aided by this program differs significantly from conventional DMFC designs and offers compelling advantages in the areas of performance, life, size, and simplicity. The program has progressed as planned resulting in the completion of the scope of work and available funding in December 2008. All 18 of the final P3 prototypes builds have been tested and the results showed significant improvements over P2 prototypes in build yield, initial performance, and durability. The systems have

  9. The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells

    PubMed Central

    Zeidler, R; Mysliwietz, J; Csánady, M; Walz, A; Ziegler, I; Schmitt, B; Wollenberg, B; Lindhofer, H

    2000-01-01

    Bispecific antibodies (bsAb) are considered as promising tools for the elimination of disseminated tumour cells in a minimal residual disease situation. The bsAb-mediated recruitment of an immune effector cell in close vicinity of a tumour cell is thought to induce an antitumoural immune response. However, classical bispecific molecules activate only a single class of immune effector cell that may not yield optimal immune responses. We therefore constructed an intact bispecific antibody, BiUII (anti-CD3 × anti-EpCAM), that not only recognizes tumour cells and T lymphocytes with its two binding arms, but also binds and activates Fcγ-receptor positive accessory cells through its Fc-region. We have demonstrated recently that activated accessory cells contribute to the bsAb-induced antitumoural activity. We now analyse this stimulation in more detail and demonstrate here the BiUll-induced upregulation of activation markers like CD83 and CD95 on accessory cells and the induction of neopterin and biopterin synthesis. Experiments with pure cell subpopulations revealed binding of BiUll to CD64+ accessory cells and CD16+ NK cells, but not to CD32+ B lymphocytes. We provide further evidence for the importance of the Fc-region in that this bispecific molecule stimulates Fcγ-R-positive accessory cells to eliminate tumour cells in vitro by direct phagocytosis. © 2000 Cancer Research Campaign PMID:10901380

  10. Resolving the active versus passive conundrum for head direction cells.

    PubMed

    Shinder, M E; Taube, J S

    2014-06-13

    Head direction (HD) cells have been identified in a number of limbic system structures. These cells encode the animal's perceived directional heading in the horizontal plane and are dependent on an intact vestibular system. Previous studies have reported that the responses of vestibular neurons within the vestibular nuclei are markedly attenuated when an animal makes a volitional head turn compared to passive rotation. This finding presents a conundrum in that if vestibular responses are suppressed during an active head turn how is a vestibular signal propagated forward to drive and update the HD signal? This review identifies and discusses four possible mechanisms that could resolve this problem. These mechanisms are: (1) the ascending vestibular signal is generated by more than just vestibular-only neurons, (2) not all vestibular-only neurons contributing to the HD pathway have firing rates that are attenuated by active head turns, (3) the ascending pathway may be spared from the affects of the attenuation in that the HD system receives information from other vestibular brainstem sites that do not include vestibular-only cells, and (4) the ascending signal is affected by the inhibited vestibular signal during an active head turn, but the HD circuit compensates and uses the altered signal to accurately update the current HD. Future studies will be needed to decipher which of these possibilities is correct.

  11. Directing the assembly of nanostructured films with living cells

    NASA Astrophysics Data System (ADS)

    Brinker, C. Jeffrey

    2007-03-01

    This talk describes our recent discovery of the ability of living cells to organize extended nanostructures and nano-objects in a manner that creates a unique, highly biocompatible nano//bio interface (Science 313, 337-340, 2006). We find that, using short chain phospholipids to direct the formation of thin film silica mesophases during evaporation-induced self-assembly, the introduction of cells (so far yeast and bacteria) alters profoundly the inorganic self-assembly pathway. Cells actively organize around themselves an ordered, multilayered lipid-membrane that interfaces coherently with a lipid-templated silica mesophase. This bio/nano interface is unique in that it withstands drying (even evacuation) without cracking or the development of tensile stresses -- yet it maintains accessibility to molecules, proteins/antibodies, plasmids, etc - introduced into the 3D silica host. Additionally cell viability is preserved for weeks to months in the absence of buffer, making these constructs useful as standalone cell-based sensors. The bio/nano interfaces we describe do not form `passively' -- rather they are a consequence of the cell's ability to sense and actively respond to external stimuli. During EISA, solvent evaporation concentrates the extracellular environment in osmolytes. In response to this hyperosmotic stress, the cells release water, creating a gradient in pH, which is maintained within the adjoining nanostructured host and serves to localize lipids, proteins, plasmids, lipidized nanocrystals, and a variety of other components at the cellular surface. This active organization of the bio/nano interface can be accomplished during ink-jet printing or selective wetting -- processes allowing patterning of cellular arrays - and even spatially-defined genetic modification.

  12. Spatially patterned matrix elasticity directs stem cell fate

    NASA Astrophysics Data System (ADS)

    Yang, Chun; DelRio, Frank W.; Ma, Hao; Killaars, Anouk R.; Basta, Lena P.; Kyburz, Kyle A.; Anseth, Kristi S.

    2016-08-01

    There is a growing appreciation for the functional role of matrix mechanics in regulating stem cell self-renewal and differentiation processes. However, it is largely unknown how subcellular, spatial mechanical variations in the local extracellular environment mediate intracellular signal transduction and direct cell fate. Here, the effect of spatial distribution, magnitude, and organization of subcellular matrix mechanical properties on human mesenchymal stem cell (hMSCs) function was investigated. Exploiting a photodegradation reaction, a hydrogel cell culture substrate was fabricated with regions of spatially varied and distinct mechanical properties, which were subsequently mapped and quantified by atomic force microscopy (AFM). The variations in the underlying matrix mechanics were found to regulate cellular adhesion and transcriptional events. Highly spread, elongated morphologies and higher Yes-associated protein (YAP) activation were observed in hMSCs seeded on hydrogels with higher concentrations of stiff regions in a dose-dependent manner. However, when the spatial organization of the mechanically stiff regions was altered from a regular to randomized pattern, lower levels of YAP activation with smaller and more rounded cell morphologies were induced in hMSCs. We infer from these results that irregular, disorganized variations in matrix mechanics, compared with regular patterns, appear to disrupt actin organization, and lead to different cell fates; this was verified by observations of lower alkaline phosphatase (ALP) activity and higher expression of CD105, a stem cell marker, in hMSCs in random versus regular patterns of mechanical properties. Collectively, this material platform has allowed innovative experiments to elucidate a novel spatial mechanical dosing mechanism that correlates to both the magnitude and organization of spatial stiffness.

  13. Spatially patterned matrix elasticity directs stem cell fate

    PubMed Central

    Yang, Chun; DelRio, Frank W.; Ma, Hao; Killaars, Anouk R.; Basta, Lena P.; Kyburz, Kyle A.; Anseth, Kristi S.

    2016-01-01

    There is a growing appreciation for the functional role of matrix mechanics in regulating stem cell self-renewal and differentiation processes. However, it is largely unknown how subcellular, spatial mechanical variations in the local extracellular environment mediate intracellular signal transduction and direct cell fate. Here, the effect of spatial distribution, magnitude, and organization of subcellular matrix mechanical properties on human mesenchymal stem cell (hMSCs) function was investigated. Exploiting a photodegradation reaction, a hydrogel cell culture substrate was fabricated with regions of spatially varied and distinct mechanical properties, which were subsequently mapped and quantified by atomic force microscopy (AFM). The variations in the underlying matrix mechanics were found to regulate cellular adhesion and transcriptional events. Highly spread, elongated morphologies and higher Yes-associated protein (YAP) activation were observed in hMSCs seeded on hydrogels with higher concentrations of stiff regions in a dose-dependent manner. However, when the spatial organization of the mechanically stiff regions was altered from a regular to randomized pattern, lower levels of YAP activation with smaller and more rounded cell morphologies were induced in hMSCs. We infer from these results that irregular, disorganized variations in matrix mechanics, compared with regular patterns, appear to disrupt actin organization, and lead to different cell fates; this was verified by observations of lower alkaline phosphatase (ALP) activity and higher expression of CD105, a stem cell marker, in hMSCs in random versus regular patterns of mechanical properties. Collectively, this material platform has allowed innovative experiments to elucidate a novel spatial mechanical dosing mechanism that correlates to both the magnitude and organization of spatial stiffness. PMID:27436901

  14. The directed differentiation of human iPS cells into kidney podocytes.

    PubMed

    Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D

    2012-01-01

    The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.

  15. Anode catalysts for direct ethanol fuel cells utilizing directly solar light illumination.

    PubMed

    Chu, Daobao; Wang, Shuxi; Zheng, Peng; Wang, Jian; Zha, Longwu; Hou, Yuanyuan; He, Jianguo; Xiao, Ying; Lin, Huashui; Tian, Zhaowu

    2009-01-01

    Shine a light: A PtNiRu/TiO(2) anode catalyst for direct ethanol fuel cells shows photocatalytic activity. The peak current density for ethanol oxidation under solar light illumination is 2-3 times greater than that in the absence of solar light. Ethanol is oxidized by light-generated holes, and the electrons are collected by the TiO(2) support to generate the oxidation current.Novel PtNiRu/TiO(2) anode catalysts for direct ethanol fuel cells (DEFCs) were prepared from PtNiRu nanoparticles (1:1:1 atomic ratios) and a nanoporous TiO(2) film by a sol-gel and electrodeposition method. The performances of the catalysts for ethanol oxidation were investigated by cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy. The results indicate a remarkable enhancement of activity for ethanol oxidation under solar light illumination. Under solar light illumination, the generated oxidation peak current density is 24.6 mA cm(-2), which is about 2.5 times higher than that observed without solar light (9.9 mA cm(-2)). The high catalytic activity of the PtNiRu/TiO(2) complex catalyst for the electrooxidation of ethanol may be attributed to the modified metal/nanoporous TiO(2) film, and the enhanced electrooxidation of ethanol under solar light may be due to the photogeneration of holes in the modified nanoporous TiO(2) film.

  16. Tuning cell adhesion by direct nanostructuring silicon into cell repulsive/adhesive patterns.

    PubMed

    Premnath, Priyatha; Tavangar, Amirhossein; Tan, Bo; Venkatakrishnan, Krishnan

    2015-09-10

    Developing platforms that allow tuning cell functionality through incorporating physical, chemical, or mechanical cues onto the material surfaces is one of the key challenges in research in the field of biomaterials. In this respect, various approaches have been proposed and numerous structures have been developed on a variety of materials. Most of these approaches, however, demand a multistep process or post-chemical treatment. Therefore, a simple approach would be desirable to develop bio-functionalized platforms for effectively modulating cell adhesion and consequently programming cell functionality without requiring any chemical or biological surface treatment. This study introduces a versatile yet simple laser approach to structure silicon (Si) chips into cytophobic/cytophilic patterns in order to modulate cell adhesion and proliferation. These patterns are fabricated on platforms through direct laser processing of Si substrates, which renders a desired computer-generated configuration into patterns. We investigate the morphology, chemistry, and wettability of the platform surfaces. Subsequently, we study the functionality of the fabricated platforms on modulating cervical cancer cells (HeLa) behaviour. The results from in vitro studies suggest that the nanostructures efficiently repel HeLa cells and drive them to migrate onto untreated sites. The study of the morphology of the cells reveals that cells evade the cytophobic area by bending and changing direction. Additionally, cell patterning, cell directionality, cell channelling, and cell trapping are achieved by developing different platforms with specific patterns. The flexibility and controllability of this approach to effectively structure Si substrates to cell-repulsive and cell-adhesive patterns offer perceptible outlook for developing bio-functionalized platforms for a variety of biomedical devices. Moreover, this approach could pave the way for developing anti-cancer platforms that selectively repel

  17. Tree ring evidence for limited direct CO2 fertilization of forests over the 20th century

    NASA Astrophysics Data System (ADS)

    Gedalof, Ze'ev; Berg, Aaron A.

    2010-09-01

    The effect that rising atmospheric CO2 levels will have on forest productivity and water use efficiency remains uncertain, yet it has critical implications for future rates of carbon sequestration and forest distributions. Efforts to understand the effect that rising CO2 will have on forests are largely based on growth chamber studies of seedlings, and the relatively small number of FACE sites. Inferences from these studies are limited by their generally short durations, artificial growing conditions, unnatural step-increases in CO2 concentrations, and poor replication. Here we analyze the global record of annual radial tree growth, derived from the International Tree ring Data Bank (ITRDB), for evidence of increasing growth rates that cannot be explained by climatic change alone, and for evidence of decreasing sensitivity to drought. We find that approximately 20 percent of sites globally exhibit increasing trends in growth that cannot be attributed to climatic causes, nitrogen deposition, elevation, or latitude, which we attribute to a direct CO2 fertilization effect. No differences were found between species in their likelihood to exhibit growth increases attributable to CO2 fertilization, although Douglas-fir (Pseudotsuga menziesii) and ponderosa pine (Pinus ponderosa), the two most commonly sampled species in the ITRDB, exhibit a CO2 fertilization signal at frequencies very near their upper and lower confidence limits respectively. Overall these results suggest that CO2 fertilization of forests will not counteract emissions or slow warming in any substantial fashion, but do suggest that future forest dynamics may differ from those seen today depending on site conditions and individual species' responses to elevated CO2.

  18. First Direct Evidence for Matter Enhanced Neutrino Oscillation, Using Super-Kamiokande Solar Neutrino Data

    NASA Astrophysics Data System (ADS)

    Renshaw, Andrew Lee

    Super-Kamiokande-IV has proven to be the largest and most precise SK data set yet. The data from this fourth phase of SK are combined with data from the previous three phases to give an extracted solar neutrino flux between 4.0 and 19.5 MeV (recoil electron kinetic energy) as (2.37+/-0.015(stat.)+/-0.04(syst.)) x 106cm-2sec-1. The SK combined recoil electron energy spectrum slightly favors a distorted shape over a flat shape. Comparing the day and night solar neutrino interactions rates separately, SK measures the day/night asymmetry as (-4.2+/-1.2+/-0.8)%. A maximum likelihood fit to the amplitude of the expected solar zenith angle variation of the neutrino-electron elastic scattering rate in SK, results in a day/night asymmetry of (-3.2+/-1.1+/-0.5)%. These results give 2.8 and 2.7 sigma significance for a non-zero day/night asymmetry. This is not only the first evidence for the regeneration of electron type solar neutrinos as they travel through Earth's matter, but the first direct evidence for matter enhanced neutrino oscillation of any kind. SK solar neutrino data measures the solar mixing angle as sin2theta12 = 0.341+0.029/-0.025, and the solar neutrino mass squared splitting as Deltam2/21=(4.8 +1.8/-0.9) x 10-5 eV2. When these results are combined with data from other solar neutrino experiments and the KamLAND experiment, sin2theta12 = 0.304+/-0.013 and Deltam2/21 = (7.45 +0.20/-0.19) x 10-5 eV2 give the most precise measurements to date.

  19. Novel Materials for High Efficiency Direct Methanol Fuel Cells

    SciTech Connect

    Carson, Stephen; Mountz, David; He, Wensheng; Zhang, Tao

    2013-12-31

    Direct methanol fuel cell membranes were developed using blends of different polyelectrolytes with PVDF. The membranes showed complex relationships between polyelectrolyte chemistry, morphology, and processing. Although the PVDF grade was found to have little effect on the membrane permselectivity, it does impact membrane conductivity and methanol permeation values. Other factors, such as varying the polyelectrolyte polarity, using varying crosslinking agents, and adjusting the equivalent weight of the membranes impacted methanol permeation, permselectivity, and areal resistance. We now understand, within the scope of the project work completed, how these inter-related performance properties can be tailored to achieve a balance of performance.

  20. Starting characteristics of direct current motors powered by solar cells

    NASA Technical Reports Server (NTRS)

    Singer, S.; Appelbaum, J.

    1989-01-01

    Direct current motors are used in photovoltaic systems. Important characteristics of electric motors are the starting to rated current and torque ratios. These ratios are dictated by the size of the solar cell array and are different for the various dc motor types. Discussed here is the calculation of the starting to rated current ratio and starting to rated torque ratio of the permanent magnet, and series and shunt excited motors when powered by solar cells for two cases: with and without a maximum-power-point-tracker (MPPT) included in the system. Comparing these two cases, one gets a torque magnification of about 3 for the permanent magnet motor and about 7 for other motor types. The calculation of the torques may assist the PV system designer to determine whether or not to include an MPPT in the system.

  1. Complex Roles of Microglial Cells in Ischemic Stroke Pathobiology: New Insights and Future Directions

    PubMed Central

    Guruswamy, Revathy; ElAli, Ayman

    2017-01-01

    Ischemic stroke constitutes the major cause of death and disability in the industrialized world. The interest in microglia arose from the evidence outlining the role of neuroinflammation in ischemic stroke pathobiology. Microglia constitute the powerhouse of innate immunity in the brain. Microglial cells are highly ramified, and use these ramifications as sentinels to detect changes in brain homeostasis. Once a danger signal is recognized, cells become activated and mount specialized responses that range from eliminating cell debris to secreting inflammatory signals and trophic factors. Originally, it was suggested that microglia play essentially a detrimental role in ischemic stroke. However, recent reports are providing evidence that the role of these cells is more complex than what was originally thought. Although these cells play detrimental role in the acute phase, they are required for tissue regeneration in the post-acute phases. This complex role of microglia in ischemic stroke pathobiology constitutes a major challenge for the development of efficient immunomodulatory therapies. This review aims at providing an overview regarding the role of resident microglia and peripherally recruited macrophages in ischemic pathobiology. Furthermore, the review will highlight future directions towards the development of novel fine-tuning immunomodulatory therapeutic interventions. PMID:28245599

  2. The core planar cell polarity gene, Vangl2, directs adult corneal epithelial cell alignment and migration

    PubMed Central

    Findlay, Amy S.; Panzica, D. Alessio; Walczysko, Petr; Holt, Amy B.; Henderson, Deborah J.; West, John D.; Rajnicek, Ann M.

    2016-01-01

    This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro. Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration. PMID:27853583

  3. Direct determination of phosphatase activity from physiological substrates in cells.

    PubMed

    Ren, Zhongyuan; Do, Le Duy; Bechkoff, Géraldine; Mebarek, Saida; Keloglu, Nermin; Ahamada, Saandia; Meena, Saurabh; Magne, David; Pikula, Slawomir; Wu, Yuqing; Buchet, René

    2015-01-01

    A direct and continuous approach to determine simultaneously protein and phosphate concentrations in cells and kinetics of phosphate release from physiological substrates by cells without any labeling has been developed. Among the enzymes having a phosphatase activity, tissue non-specific alkaline phosphatase (TNAP) performs indispensable, multiple functions in humans. It is expressed in numerous tissues with high levels detected in bones, liver and neurons. It is absolutely required for bone mineralization and also necessary for neurotransmitter synthesis. We provided the proof of concept that infrared spectroscopy is a reliable assay to determine a phosphatase activity in the osteoblasts. For the first time, an overall specific phosphatase activity in cells was determined in a single step by measuring simultaneously protein and substrate concentrations. We found specific activities in osteoblast like cells amounting to 116 ± 13 nmol min(-1) mg(-1) for PPi, to 56 ± 11 nmol min(-1) mg(-1) for AMP, to 79 ± 23 nmol min(-1) mg(-1) for beta-glycerophosphate and to 73 ± 15 nmol min(-1) mg(-1) for 1-alpha-D glucose phosphate. The assay was also effective to monitor phosphatase activity in primary osteoblasts and in matrix vesicles. The use of levamisole--a TNAP inhibitor--served to demonstrate that a part of the phosphatase activity originated from this enzyme. An IC50 value of 1.16 ± 0.03 mM was obtained for the inhibition of phosphatase activity of levamisole in osteoblast like cells. The infrared assay could be extended to determine any type of phosphatase activity in other cells. It may serve as a metabolomic tool to monitor an overall phosphatase activity including acid phosphatases or other related enzymes.

  4. Direct fuel cells: Putting power where you need it!

    SciTech Connect

    Glenn, D.R.

    1996-12-31

    The world`s largest capacity carbonate fuel cell power plant is expected to commence operation at a substation located in California on the City of Santa Clara`s electric system in the first half of 1996. With a nominal capacity of two megawatts (1.8-MW delivered), the plant is a first-of-a-kind demonstration of a power system based on an internally-reforming fuel cell technology called the Direct Fuel Cell (DFC), developed by the Energy Research Corporation (ERC). As important as the introduction of the technology itself, is its use in a distributed generation strategy. The power plant being demonstrated at Santa Clara is an enabling technology to advance the applicability of locally-sited generation usually at smaller scales, say 1-6 megawatts, near served loads. This is not a new idea as it relates to previous incarnations as total energy systems or cogenerators, where the by-product heat from the usually inefficient combustion-driven generator is recovered and applied for spaceheating, raising steam, etc. What makes the fuel cell-based system special is that it operates quietly, emits virtually no pollution, and converts the energy value of the inlet gaseous fuel(s) to electricity electrochemically (non-Carnot cycle limited). For the ERC technology, this translates to attainable electric efficiencies of over 50%, or heat rates of less than 6800 BTU/kWh, even in smaller size equipment.

  5. Performance of direct methanol polymer electrolyte fuel cell

    SciTech Connect

    Shin, Dong Ryul; Jung, Doo Hwan; Lee, Chang Hyeong; Chun, Young Gab

    1996-12-31

    Direct methanol fuel cells (DMFC) using polymer electrolyte membrane are promising candidate for application of portable power sources and transportation applications because they do not require any fuel processing equipment and can be operated at low temperature of 60{degrees}C - 130{degrees}C. Elimination of the fuel processor results in simpler design, higher operation reliability, lower weight volume, and lower capital and operating cost. However, methanol as a fuel is relatively electrochemical inert, so that kinetics of the methanol oxidation is too slow. Platinum and Pt-based binary alloy electrodes have been extensively studied for methanol electro-oxidation in acid electrolyte at ambient and elevated temperatures. Particularly, unsupported carbon Pt-Ru catalyst was found to be superior to the anode of DMFC using a proton exchange membrane electrolyte (Nafion). The objective of this study is to develop the high performance DNTC. This paper summarizes the results from half cell and single cell tests, which focus on the electrode manufacturing process, catalyst selection, and operating conditions of single cell such as methanol concentration, temperature and pressure.

  6. Anionic-cationic bi-cell design for direct methanol fuel cell stack

    NASA Astrophysics Data System (ADS)

    Kim, Hyea; Ünlü, Murat; Zhou, Junfeng; Anestis-Richard, Irene; Kohl, Paul A.

    A new fuel cell stack design is described using an anion exchange membrane (AEM) fuel cell and a proton exchange membrane (PEM) fuel cell in series with a single fuel tank servicing both anodes in a passive direct methanol fuel cell configuration. The anionic-cationic bi-cell stack has alkaline and acid fuel cells in series (twice the voltage), one fuel tank, and simplified water management. The series connection between the two cells involves shorting the cathode of the anionic cell to the anode of the acidic cell. It is shown that these two electrodes are at essentially the same potential which avoids an undesired potential difference and resulting loss in current between the two electrodes. Further, the complimentary direction of water transport in the two kinds of fuel cells simplifies water management at both the anodes and cathodes. The effect of ionomer content on the AEM electrode potential and the activity of methanol oxidation were investigated. The individual performance of AEM and PEM fuel cells were evaluated. The effect of ion-exchange capacity in the alkaline electrodes was studied. A fuel wicking material in the methanol fuel tank was used to provide orientation-independent operation. The open circuit potential of the bi-cell was 1.36 V with 2.0 M methanol fuel and air at room temperature.

  7. Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions.

    PubMed

    Boss, Anna; Bishop, Karen S; Marlow, Gareth; Barnett, Matthew P G; Ferguson, Lynnette R

    2016-08-19

    The traditional Mediterranean diet (MD) is associated with long life and lower prevalence of cardiovascular disease and cancers. The main components of this diet include high intake of fruit, vegetables, red wine, extra virgin olive oil (EVOO) and fish, low intake of dairy and red meat. Olive oil has gained support as a key effector of health benefits and there is evidence that this relates to the polyphenol content. Olive leaf extract (OLE) contains a higher quantity and variety of polyphenols than those found in EVOO. There are also important structural differences between polyphenols from olive leaf and those from olive fruit that may improve the capacity of OLE to enhance health outcomes. Olive polyphenols have been claimed to play an important protective role in cancer and other inflammation-related diseases. Both inflammatory and cancer cell models have shown that olive leaf polyphenols are anti-inflammatory and protect against DNA damage initiated by free radicals. The various bioactive properties of olive leaf polyphenols are a plausible explanation for the inhibition of progression and development of cancers. The pathways and signaling cascades manipulated include the NF-κB inflammatory response and the oxidative stress response, but the effects of these bioactive components may also result from their action as a phytoestrogen. Due to the similar structure of the olive polyphenols to oestrogens, these have been hypothesized to interact with oestrogen receptors, thereby reducing the prevalence and progression of hormone related cancers. Evidence for the protective effect of olive polyphenols for cancer in humans remains anecdotal and clinical trials are required to substantiate these claims idea. This review aims to amalgamate the current literature regarding bioavailability and mechanisms involved in the potential anti-cancer action of olive leaf polyphenols.

  8. Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions

    PubMed Central

    Boss, Anna; Bishop, Karen S.; Marlow, Gareth; Barnett, Matthew P. G.; Ferguson, Lynnette R.

    2016-01-01

    The traditional Mediterranean diet (MD) is associated with long life and lower prevalence of cardiovascular disease and cancers. The main components of this diet include high intake of fruit, vegetables, red wine, extra virgin olive oil (EVOO) and fish, low intake of dairy and red meat. Olive oil has gained support as a key effector of health benefits and there is evidence that this relates to the polyphenol content. Olive leaf extract (OLE) contains a higher quantity and variety of polyphenols than those found in EVOO. There are also important structural differences between polyphenols from olive leaf and those from olive fruit that may improve the capacity of OLE to enhance health outcomes. Olive polyphenols have been claimed to play an important protective role in cancer and other inflammation-related diseases. Both inflammatory and cancer cell models have shown that olive leaf polyphenols are anti-inflammatory and protect against DNA damage initiated by free radicals. The various bioactive properties of olive leaf polyphenols are a plausible explanation for the inhibition of progression and development of cancers. The pathways and signaling cascades manipulated include the NF-κB inflammatory response and the oxidative stress response, but the effects of these bioactive components may also result from their action as a phytoestrogen. Due to the similar structure of the olive polyphenols to oestrogens, these have been hypothesized to interact with oestrogen receptors, thereby reducing the prevalence and progression of hormone related cancers. Evidence for the protective effect of olive polyphenols for cancer in humans remains anecdotal and clinical trials are required to substantiate these claims idea. This review aims to amalgamate the current literature regarding bioavailability and mechanisms involved in the potential anti-cancer action of olive leaf polyphenols. PMID:27548217

  9. First evidence for a direct inhibitory effect of kisspeptins on LH expression in the eel, Anguilla anguilla.

    PubMed

    Pasquier, J; Lafont, A-G; Leprince, J; Vaudry, H; Rousseau, K; Dufour, S

    2011-08-01

    The kisspeptin system has emerged as one of the main puberty gatekeepers among vertebrates. The European eel (Anguilla anguilla) is a remarkable model due to its phylogenetical position at the basis of teleosts, and its unique life cycle with a blockade of puberty before reproductive migration. We cloned the full-length coding sequence of a kisspeptin receptor (Kissr) in the eel. Comparison of Kissr sequences assigned the eel Kissr to a basal position in a clade including most of the known teleost Kissr, in agreement with the eel phylogenetical position. Eel Kissr tissue distribution was analyzed by quantitative real-time PCR. Eel Kissr was highly expressed in the brain, especially in the telencephalon and di-/mes-encephalon, while a very low or undetectable expression was observed in various peripheral organs. A high expression of Kissr was also found in the pituitary indicating a possible direct pituitary role of kisspeptin. Primary cultures of eel pituitary cells were performed to investigate the direct effects of kisspeptin on pituitary hormone expression. Human/lamprey kisspeptin exerted a time- and dose-dependent inhibitory effect on LHβ expression. All other tested kisspeptins had a similar inhibitory effect on LHβ expression. The inhibitory effect of kisspeptins was exerted specifically on LHβ as no change was induced on the expression of other glycoprotein hormone subunits (GPα, FSHβ and TSHβ) nor of growth hormone. These data provide the first evidence for the existence, in the European eel, of a kisspeptin system, which may play a direct inhibitory role on pituitary LHβ expression.

  10. Nanotopography guides and directs cell migration in amoeboid and epithelial cells

    NASA Astrophysics Data System (ADS)

    Lee, Rachel; Das, Satarupa; Hourwitz, Matthew; Sun, Xiaoyu; Parent, Carole; Fourkas, John; Losert, Wolfgang

    Cell migration plays a critical role in development, angiogenesis, immune response, wound healing, and cancer metastasis. In many cases, cells also move in the context of a matrix of collagen fibers, and the alignment of these fibers can both affect the migration phenotype and guide cells. Here we show that both fast and slow migrating cells - amoeboid HL-60 and epithelial MCF10A - are affected in similar ways by micro/nanostructures with dimensions similar to those of collagen fibers. Cell alignment enhances the efficiency of migration by increasing directional persistence.

  11. Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders

    PubMed Central

    Hou, Shaoping; Lu, Paul

    2016-01-01

    Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders. PMID:26981072

  12. Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells

    PubMed Central

    Cieślar-Pobuda, Artur; Rafat, Mehrdad; Knoflach, Viktoria; Skonieczna, Magdalena; Hudecki, Andrzej; Małecki, Andrzej; Urasińska, Elżbieta; Ghavami, Seaid; Łos, Marek J.

    2016-01-01

    The corneal epithelium is maintained by a small pool of tissue stem cells located at the limbus. Through certain injuries or diseases this pool of stem cells may get depleted. This leads to visual impairment. Standard treatment options include autologous or allogeneic limbal stem cell (LSC) transplantation, however graft rejection and chronic inflammation lowers the success rate over long time. Induced pluripotent stem (iPS) cells have opened new possibilities for treating various diseases with patient specific cells, eliminating the risk of immune rejection. In recent years, several protocols have been developed, aimed at the differentiation of iPS cells into the corneal epithelial lineage by mimicking the environmental niche of limbal stem cells. However, the risk of teratoma formation associated with the use of iPS cells hinders most applications from lab into clinics. Here we show that the differentiation of iPS cells into corneal epithelial cells results in the expression of corneal epithelial markers showing a successful differentiation, but the process is long and the level of gene expression for the pluripotency markers does not vanish completely. Therefore we set out to determine a direct transdifferentiation approach to circumvent the intermediate state of pluripotency (iPS-stage). The resulting cells, obtained by direct transdifferentiation of fibroblasts into limbal cells, exhibited corneal epithelial cell morphology and expressed corneal epithelial markers. Hence we shows for the first time a direct transdifferentiation of human dermal fibroblasts into the corneal epithelial lineage that may serve as source for corneal epithelial cells for transplantation approaches. PMID:27275539

  13. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions.

    PubMed

    Lee, Dae-Won; Lee, Kyung-Hun; Kim, Jin Wook; Keam, Bhumsuk

    2016-07-05

    Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.

  14. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions

    PubMed Central

    Lee, Dae-Won; Lee, Kyung-Hun; Kim, Jin Wook; Keam, Bhumsuk

    2016-01-01

    Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC. PMID:27399673

  15. Improved Anode for a Direct Methanol Fuel Cell

    NASA Technical Reports Server (NTRS)

    Valdez, Thomas; Narayanan, Sekharipuram

    2005-01-01

    A modified chemical composition has been devised to improve the performance of the anode of a direct methanol fuel cell. The main feature of the modified composition is the incorporation of hydrous ruthenium oxide into the anode structure. This modification can reduce the internal electrical resistance of the cell and increase the degree of utilization of the anode catalyst. As a result, a higher anode current density can be sustained with a smaller amount of anode catalyst. These improvements can translate into a smaller fuel-cell system and higher efficiency of conversion. Some background information is helpful for understanding the benefit afforded by the addition of hydrous ruthenium oxide. The anode of a direct methanol fuel cell sustains the electro-oxidation of methanol to carbon dioxide in the reaction CH3OH + H2O--->CO2 + 6H(+) + 6e(-). An electrocatalyst is needed to enable this reaction to occur. The catalyst that offers the highest activity is an alloy of approximately equal numbers of atoms of the noble metals platinum and ruthenium. The anode is made of a composite material that includes high-surface-area Pt/Ru alloy particles and a proton-conducting ionomeric material. This composite is usually deposited onto a polymer-electrolyte (proton-conducting) membrane and onto an anode gas-diffusion/current-collector sheet that is subsequently bonded to the proton-conducting membrane by hot pressing. Heretofore, the areal density of noble-metal catalyst typically needed for high performance has been about 8 mg/cm2. However, not all of the catalyst has been utilized in the catalyzed electro-oxidation reaction. Increasing the degree of utilization of the catalyst would make it possible to improve the performance of the cell for a given catalyst loading and/or reduce the catalyst loading (thereby reducing the cost of the cell). The use of carbon and possibly other electronic conductors in the catalyst layer has been proposed for increasing the utilization of the

  16. Evidence for the direct oxidation of organic nitrogen to N2 gas in the Arabian Sea.

    PubMed

    Trimmer, Mark; Purdy, Kevin J

    2012-09-01

    We performed a suite of (15)N incubations ((15)NO(2)(-), (15)NO(3)(-) and (15)NH(4)(+)) with and without the organic-nitrogen (N) compound allylthiourea (ATU), in the suboxic waters of the Arabian Sea. Production of (29)N(2) in control (-ATU) incubations with either (15)NH(4)(+)+(14)NO(2)(-), or their analogues, (15)NO(2)(-)+(14)NH(4)(+), though small, confirmed the presence of anammox. In contrast, when we added ATU, along with (15)NO(2)(-) and (14)NH(4)(+), there was a much greater production of (29)N(2), with 92% of the (15)N-label being recovered as (29)N(2) on average. Such stimulated production of (29)N(2) could not be due to anammox, as the addition of ATU, along with (15)NH(4)(+)+(14)NO(2)(-), only produced (29)N(2) equivalent to that in the controls. The ratios of (29)N(2) to (30)N(2) produced also precluded stimulation of denitrification. We present this as evidence for a hitherto uncharacterised metabolism potentially capable of oxidising organic-N (e.g. NH(2) groups) directly to N(2) gas at the expense of NO(2)(-).

  17. Molecular Evidence for a Natural Primary Triple Hybrid in Plants Revealed from Direct Sequencing

    PubMed Central

    Kaplan, Zdenek; Fehrer, Judith

    2007-01-01

    Background and Aims Molecular evidence for natural primary hybrids composed of three different plant species is very rarely reported. An investigation was therefore carried out into the origin and a possible scenario for the rise of a sterile plant clone showing a combination of diagnostic morphological features of three separate, well-defined Potamogeton species. Methods The combination of sequences from maternally inherited cytoplasmic (rpl20-rps12) and biparentally inherited nuclear ribosomal DNA (ITS) was used to identify the exact identity of the putative triple hybrid. Key Results Direct sequencing showed ITS variants of three parental taxa, P. gramineus, P. lucens and P. perfoliatus, whereas chloroplast DNA identified P. perfoliatus as the female parent. A scenario for the rise of the triple hybrid through a fertile binary hybrid P. gramineus × P. lucens crossed with P. perfoliatus is described. Conclusions Even though the triple hybrid is sterile, it possesses an efficient strategy for its existence and became locally successful even in the parental environment, perhaps as a result of heterosis. The population investigated is the only one known of this hybrid, P. × torssanderi, worldwide. Isozyme analysis indicated the colony to be genetically uniform. The plants studied represented a single clone that seems to have persisted at this site for a long time. PMID:17478544

  18. PLASMA OXYTOCIN CONCENTRATION AND DEPRESSIVE SYMPTOMS: A REVIEW OF CURRENT EVIDENCE AND DIRECTIONS FOR FUTURE RESEARCH.

    PubMed

    Massey, Suena H; Backes, Katherine A; Schuette, Stephanie A

    2016-04-01

    There is substantial recent interest in the role of oxytocin in social and affiliative behaviors-animal models of depression have suggested a link between oxytocin and mood. We reviewed literature to date for evidence of a potential relationship between peripheral oxytocin concentration and depressive symptoms in humans. Pubmed(®) and PsychINFO(®) were searched for biomedical and social sciences literature from 1960 to May 19, 2015 for empirical articles in English involving human subjects focused on the relationship between peripheral oxytocin concentration and depressive symptoms, excluding articles on the oxytocin receptor gene, or involving exogenous (i.e. intranasal) administration of oxytocin. Eight studies meeting criteria were identified and formally reviewed. Studies of pregnant women suggested an inverse relationship between oxytocin level and depressive symptom severity. Findings in nonpregnant women were broadly consistent with the role of oxytocin release in response to stress supported by animal studies. The relationship between oxytocin and depression in men appeared to be in the opposite direction, possibly reflecting the influence of gonadal hormones on oxytocinergic functioning found in other mammalian species. Overall, small sample sizes, heterogeneity in study designs, and other methodological limitations may account for inconsistent findings. Future research utilizing reliable oxytocin measurement protocols including measurements across time, larger sample sizes, and sample homogeneity with respect to multiple possible confounders (age, gender, race and ethnicity, ovarian status among women, and psychosocial context) are needed to elucidate the role of oxytocin in the pathogenesis of depression, and could guide the design of novel pharmacologic agents.

  19. Direct evidence for the adaptive role of copy number variation on antifolate susceptibility in Plasmodium falciparum

    PubMed Central

    Heinberg, Adina; Siu, Edwin; Stern, Chaya; Lawrence, Elizabeth A; Ferdig, Michael T; Deitsch, Kirk W; Kirkman, Laura A

    2013-01-01

    Summary Resistance to antimalarials targeting the folate pathway is widespread. GTP-cyclohydrolase (gch1), the first enzyme in this pathway, exhibits extensive copy number variation (CNV) in parasite isolates from areas with a history of longstanding antifolate use. Increased CN of gch1 is associated with a greater number of point mutations in enzymes targeted by the antifolates, pyrimethamine and sulfadoxine. While these observations suggest that increases in gch1 CN are an adaptation to drug pressure, changes in CN have not been experimentally demonstrated to directly alter drug susceptibility. To determine if changes in gch1 expression alone modify pyrimethamine sensitivity, we manipulated gch1 CN in several parasite lines to test the effect on drug sensitivity. We report that increases in gch1 CN alter pyrimethamine resistance in most parasites lines. However we find evidence of a detrimental effect of very high levels of gch1 overexpression in parasite lines with high endogenous levels of gch1 expression, revealing the importance of maintaining balance in the folate pathway and implicating changes in gch1 expression in preserving proper metabolic flux. This work expands our understanding of parasite adaptation to drug pressure and provides a possible mechanism for how specific mutations become fixed within parasite populations. PMID:23347134

  20. Kodiak brown bears surf the salmon red wave: direct evidence from GPS collared individuals.

    PubMed

    Deacy, William; Leacock, William; Armstrong, Jonathan B; Stanford, Jack A

    2016-05-01

    A key constraint faced by consumers is achieving a positive energy balance in the face of temporal variation in foraging opportunities. Recent work has shown that spatial heterogeneity in resource phenology can buffer mobile consumers from this constraint by allowing them to track changes in resource availability across space. For example, salmon populations spawn asynchronously across watersheds, causing high-quality foraging opportunities to propagate across the landscape, prolonging the availability of salmon at the regional scale. However, we know little about how individual consumers integrate across phenological variation or the benefits they receive by doing so. Here, we present direct evidence that individual brown bears track spatial variation in salmon phenology. Data from 40 GPS collared brown bears show that bears visited multiple spawning sites in synchrony with the order of spawning phenology. The number of sites used was correlated with the number of days a bear exploited salmon, suggesting the phenological variation in the study area influenced bear access to salmon, a resource which strongly influences bear fitness. Fisheries managers attempting to maximize harvest while maintaining ecosystem function should strive to protect the population diversity that underlies the phenological variation used by wildlife consumers.

  1. Direct Evidence for AGN-Driven Winds in a z = 1.5 Radio Galaxy

    NASA Astrophysics Data System (ADS)

    Steinbring, Eric

    2010-05-01

    Feedback from AGN is a key component in most current models of galaxy formation and evolution. For the most massive galaxies, heating and removal of gas by the AGN could precipitate an abrupt quenching of star formation during a dramatic blow-out phase. The “smoking gun” for such a scenario would be direct evidence of powerful outflows associated with the jet. I present some preliminary results of a program to look for these in high-z radio galaxies (HzRGs). Recent observations of the z = 1.5 radio galaxy 3C 230 obtained with the NIFS integral-field spectrograph and Altair laser adaptive optics facility on Gemini North are shown. These reveal with unprecedented resolution the complex kinematics of this system in redshifted Hα and [N ii] emission. The bi-polar velocity field is aligned with the jet axis, with a kinematic center associated with the radio core itself, and turbulent edges approaching the galaxy's escape velocity. This suggests a gas mass of roughly 1011 M⊙ has been propagating outwards for 107 to 108 years, corresponding to a mass loss of roughly 102-3 M⊙ yr-1, based on its velocity and spatial extent. This is in good agreement with the energetics and typical ages of radio jets, and likely heralds the onset of the “red and dead” stage for this HzRG.

  2. Direct evidence for the semipersistent transmission of Cucurbit chlorotic yellows virus by a whitefly vector

    PubMed Central

    Li, Jingjing; Liang, Xiangzhi; Wang, Xueli; Shi, Yan; Gu, Qinsheng; Kuo, Yen-Wen; Falk, Bryce W.; Yan, Fengming

    2016-01-01

    Cucurbit chlorotic yellows virus (CCYV) (genus Crinivirus, family Closteroviridae) is an emerging plant virus, and is now spreading and causing severe economic losses to cucurbit crops in many Asian countries. CCYV is believed to be transmitted specifically by the sweetpotato whitefly, Bemisia tabaci, in a semipersistent manner. In the present study, we provide direct evidence for the semipersistent transmission of CCYV by Mediterranean (MED) cryptic species of B. tabaci complex. We investigated CCYV transmission characteristics, and immunofluorescently labeled and localized the virus retention site within the vector by laser confocal microscopy. Whiteflies required ≥1 h of acquisition access period (AAP) to successfully acquire CCYV, and the proportion of RT-PCR positive whitefly individuals reached to 100% at 48 h of AAP. CCYV virons could be retained within vectors as long as 12 d, but the proportion of RT-PCR positive whiteflies dropped to 55% by 3 d. Groups of thirty whiteflies given a 24 h of inoculation access period (IAP) to inoculate CCYV on cucumber plants showed a transmission efficiency rate of 72.73%. The retention site of CCYV virons was located in the foregut of virion-fed vectors. These results definitely indicated the semipersistent transmission mode of CCYV by B. tabaci MED. PMID:27812032

  3. Direct evidence of octupole deformation in neutron-rich 144Ba

    SciTech Connect

    Bucher, B.; Zhu, S.; Wu, C. Y.; Janssens, R. V. F.; Cline, D.; Hayes, A. B.; Albers, M.; Ayangeakaa, A. D.; Butler, P. A.; Campbell, C. M.; Carpenter, M. P.; Chiara, C. J.; Clark, J.; Crawford, H. L.; Cromaz, M.; David, H. M.; Gregor, E. T.; Kondev, F. G.; Harker, J.; Hoffman, C. R.; Kay, B. P.; Korichi, A.; Lauritsen, T.; Macchiavelli, A. O.; Pardo, R. C.; Richard, A.; Riley, M. A.; Savard, G.; Scheck, M.; Seweryniak, D.; Smith, M. K.; Wiens, A.; Vondrasek, R.

    2016-03-17

    Here, the neutron-rich nucleus 144Ba (t1/2 = 11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV 144Ba beam on a 1.0–mg/cm2 208Pb target. The measured value of the matrix element, < 31–∥M(E3)∥01+ >= 0.65(+17–23) eb3/2, corresponds to a reduced B(E3) transition probability of 48(+25–34) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.

  4. Direct evidence of meddy formation off the southwestern coast of Portugal

    NASA Astrophysics Data System (ADS)

    Bower, Amy S.; Armi, Laurence; Ambar, Isabel

    1995-09-01

    The formation of a Mediterranean Water eddy, or meddy, was observed directly for the first time off the southwestern coast of Portugal near Cape St. Vincent. The formation event is revealed in the 30-day trajectory of a RAFOS float deployed in the lower core of the Mediterranean Undercurrent in the Gulf of Cadiz. For the first several days after deployment, this float was advected westward in the Undercurrent at a speed of about 0.4 m s -1, generally paralleling the topography. Just after passing Cape St. Vincent, where the coast turns abruptly northward, the float began looping anticyclonically, indicating that it had become trapped in the core of a new meddy. The meddy translated first westward, then southwestward along the southern flank of Gorringe Bank. The float rotated around the meddy center with azimuthal speeds of 0.20-0.25 m s -1 at a radius of about 10 km. The rotation period was on the order of three days, and the average translation speed of the meddy over 25 days was 0.08 m s -1. Observations of this and four additional 30-day trajectories indicate (1) persistent westward flow of the Undercurrent along the south coast of Portugal, (2) a tendency for the lower core of the Undercurrent to separate from the continental boundary after passing Cape St. Vincent, and (3) evidence of anticyclonic looping west of Cape St. Vincent. These preliminary results confirm the speculation that the region off Cape St. Vincent is one site of meddy generation.

  5. Direct evidence of octupole deformation in neutron-rich 144Ba

    DOE PAGES

    Bucher, B.; Zhu, S.; Wu, C. Y.; ...

    2016-03-17

    Here, the neutron-rich nucleus 144Ba (t1/2 = 11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV 144Ba beam on a 1.0–mg/cm2 208Pb target. The measured value of the matrix element, < 31–∥M(E3)∥01+ >= 0.65(+17–23) eb3/2, corresponds to a reduced B(E3) transition probabilitymore » of 48(+25–34) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.« less

  6. Direct experimental evidence for a multiparticle-hole ground state configuration of deformed 33Mg

    NASA Astrophysics Data System (ADS)

    Datta, Ushasi; Rahaman, A.; Aumann, T.; Beceiro-Novo, S.; Boretzky, K.; Caesar, C.; Carlson, B. V.; Catford, W. N.; Chakraborty, S.; Chartier, M.; Cortina-Gil, D.; de Angelis, G.; Diaz Fernandez, P.; Emling, H.; Ershova, O.; Fraile, L. M.; Geissel, H.; Gonzalez-Diaz, D.; Jonson, B.; Johansson, H.; Kalantar-Nayestanaki, N.; Kröll, T.; Krücken, R.; Kurcewicz, J.; Langer, C.; Le Bleis, T.; Leifels, Y.; Marganiec, J.; Münzenberg, G.; Najafi, M. A.; Nilsson, T.; Nociforo, C.; Panin, V.; Paschalis, S.; Plag, R.; Reifarth, R.; Ricciardi, V.; Rossi, D.; Scheit, H.; Scheidenberger, C.; Simon, H.; Taylor, J. T.; Togano, Y.; Typel, S.; Volkov, V.; Wagner, A.; Wamers, F.; Weick, H.; Weigand, M.; Winfield, J. S.; Yakorev, D.; Zoric, M.

    2016-09-01

    The first direct experimental evidence of a multiparticle-hole ground state configuration of the neutron-rich 33Mg isotope has been obtained via intermediate energy (400 A MeV) Coulomb dissociation measurement. The major part ˜(70 ±13 )% of the cross section is observed to populate the excited states of 32Mg after the Coulomb breakup of 33Mg. The shapes of the differential Coulomb dissociation cross sections in coincidence with different core excited states favor that the valence neutron occupies both the s1 /2 and p3 /2 orbitals. These experimental findings suggest a significant reduction and merging of s d -p f shell gaps at N ˜20 and 28. The ground state configuration of 33Mg is predominantly a combination of 32Mg(3.0 ,3.5 MeV ;2-,1-) ⨂νs1/2 , 32Mg(2.5 MeV ;2+) ⨂νp3/2 , and 32Mg(0 ;0+) ⨂νp3/2 . The experimentally obtained quantitative spectroscopic information for the valence neutron occupation of the s and p orbitals, coupled with different core states, is in agreement with Monte Carlo shell model (MCSM) calculation using 3 MeV as the shell gap at N =20 .

  7. Directed Forgetting in Direct and Indirect Tests of Memory: Seeking Evidence of Retrieval Inhibition Using Electrophysiological Measures

    ERIC Educational Resources Information Center

    Van Hooff, Johanna C.; Whitaker, T. Aisling; Ford, Ruth M.

    2009-01-01

    We investigated whether directed forgetting as elicited by the item-cueing method results solely from "differential rehearsal" of to-be-remembered vs. to-be-forgotten words or, additionally, from "inhibitory" processes that actively impair retrieval of to-be-forgotten words. During study, participants (N = 24) were instructed to remember half of a…

  8. Tuning cell adhesion by direct nanostructuring silicon into cell repulsive/adhesive patterns

    SciTech Connect

    Premnath, Priyatha; Venkatakrishnan, Krishnan

    2015-09-10

    Developing platforms that allow tuning cell functionality through incorporating physical, chemical, or mechanical cues onto the material surfaces is one of the key challenges in research in the field of biomaterials. In this respect, various approaches have been proposed and numerous structures have been developed on a variety of materials. Most of these approaches, however, demand a multistep process or post-chemical treatment. Therefore, a simple approach would be desirable to develop bio-functionalized platforms for effectively modulating cell adhesion and consequently programming cell functionality without requiring any chemical or biological surface treatment. This study introduces a versatile yet simple laser approach to structure silicon (Si) chips into cytophobic/cytophilic patterns in order to modulate cell adhesion and proliferation. These patterns are fabricated on platforms through direct laser processing of Si substrates, which renders a desired computer-generated configuration into patterns. We investigate the morphology, chemistry, and wettability of the platform surfaces. Subsequently, we study the functionality of the fabricated platforms on modulating cervical cancer cells (HeLa) behaviour. The results from in vitro studies suggest that the nanostructures efficiently repel HeLa cells and drive them to migrate onto untreated sites. The study of the morphology of the cells reveals that cells evade the cytophobic area by bending and changing direction. Additionally, cell patterning, cell directionality, cell channelling, and cell trapping are achieved by developing different platforms with specific patterns. The flexibility and controllability of this approach to effectively structure Si substrates to cell-repulsive and cell-adhesive patterns offer perceptible outlook for developing bio-functionalized platforms for a variety of biomedical devices. Moreover, this approach could pave the way for developing anti-cancer platforms that selectively repel

  9. Effects of Physician-directed Pharmaceutical Promotion on Prescription Behaviors: Longitudinal Evidence.

    PubMed

    Datta, Anusua; Dave, Dhaval

    2017-04-01

    Spending on prescription drugs (Rx) represents one of the fastest growing components of US healthcare spending and has coincided with an expansion of pharmaceutical promotional spending. Most (83%) of Rx promotion is directed at physicians in the form of visits by pharmaceutical representatives (known as detailing) and drug samples provided to physicians' offices. Such promotion has come under increased public scrutiny, with critics contending that physician-directed promotion may play a role in raising healthcare costs and may unduly affect physicians' prescribing habits towards more expensive, and possibly less cost-effective, drugs. In this study, we bring longitudinal evidence to bear upon the question of how detailing impacts physicians' prescribing behaviors. Specifically, we examine prescriptions and promotion for a particular drug class based on a nationally representative sample of 150,000 physicians spanning 24 months. The use of longitudinal physician-level data allows us to tackle some of the empirical concerns in the extant literature, virtually all of which have relied on aggregate national data. We estimate fixed-effects specifications that bypass stable unobserved physician-specific heterogeneity and address potential targeting bias. In addition, we also assess differential effects at both the extensive and intensive margins of prescribing behaviors and differential effects across physician-level and market-level characteristics, questions that have not been explored in prior work. The estimates suggest that detailing has a significant and positive effect on the number of new scripts written for the detailed drug, with an elasticity magnitude of 0.06. This effect is substantially smaller than those in the literature based on aggregate information, suggesting that most of the observed relationship between physician-directed promotion and drug sales is driven by selection bias. We find that detailing impacts selective brand-specific demand but does

  10. Motor-language coupling: direct evidence from early Parkinson's disease and intracranial cortical recordings.

    PubMed

    Ibáñez, Agustín; Cardona, Juan F; Dos Santos, Yamil Vidal; Blenkmann, Alejandro; Aravena, Pía; Roca, María; Hurtado, Esteban; Nerguizian, Mirna; Amoruso, Lucía; Gómez-Arévalo, Gonzalo; Chade, Anabel; Dubrovsky, Alberto; Gershanik, Oscar; Kochen, Silvia; Glenberg, Arthur; Manes, Facundo; Bekinschtein, Tristán

    2013-04-01

    Language and action systems are functionally coupled in the brain as demonstrated by converging evidence using Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS), and lesion studies. In particular, this coupling has been demonstrated using the action-sentence compatibility effect (ACE) in which motor activity and language interact. The ACE task requires participants to listen to sentences that described actions typically performed with an open hand (e.g., clapping), a closed hand (e.g., hammering), or without any hand action (neutral); and to press a large button with either an open hand position or closed hand position immediately upon comprehending each sentence. The ACE is defined as a longer reaction time (RT) in the action-sentence incompatible conditions than in the compatible conditions. Here we investigated direct motor-language coupling in two novel and uniquely informative ways. First, we measured the behavioural ACE in patients with motor impairment (early Parkinson's disease - EPD), and second, in epileptic patients with direct electrocorticography (ECoG) recordings. In experiment 1, EPD participants with preserved general cognitive repertoire, showed a much diminished ACE relative to non-EPD volunteers. Moreover, a correlation between ACE performance and action-verb processing (kissing and dancing test - KDT) was observed. Direct cortical recordings (ECoG) in motor and language areas (experiment 2) demonstrated simultaneous bidirectional effects: motor preparation affected language processing (N400 at left inferior frontal gyrus and middle/superior temporal gyrus), and language processing affected activity in movement-related areas (motor potential at premotor and M1). Our findings show that the ACE paradigm requires ongoing integration of preserved motor and language coupling (abolished in EPD) and engages motor-temporal cortices in a bidirectional way. In addition, both experiments

  11. Electrical stimulation via a biocompatible conductive polymer directs retinal progenitor cell differentiation.

    PubMed

    Saigal, Rajiv; Cimetta, Elisa; Tandon, Nina; Zhou, Jing; Langer, Robert; Young, Michael; Vunjak-Novakovic, Gordana; Redenti, Stephen

    2013-01-01

    The goal of this study was to simulate in vitro the spontaneous electrical wave activity associated with retinal development and investigate if such biometrically designed signals can enhance differentiation of mouse retinal progenitor cells (mRPC). To this end, we cultured cells on an electroconductive transplantable polymer, polypyrrole (PPy) and measured gene expression and morphology of the cells. Custom-made 8-well cell culture chambers were designed to accommodate PPy deposited onto indium tin oxide-coated (ITO) glass slides, with precise control of the PPy film thickness. mRPCs were isolated from post-natal day 1 (P1) green fluorescent protein positive (GFP+) mice, expanded, seeded onto PPY films, allowed to adhere for 24 hours, and then subjected to electrical stimulation (100 µA pulse trains, 5 s in duration, once per minute) for 4 days. Cultured cells and non-stimulated controls were processed for immunostaining and confocal analysis, and for RNA extraction and quantitative PCR. Stimulated cells expressed significantly higher levels of the early photoreceptor marker cone-rod homebox (CRX, the earliest known marker of photoreceptor identity), and protein kinase-C (PKC), and significantly lower levels of the glial fibrillary acidic protein (GFAP). Consistently, stimulated cells developed pronounced neuronal morphologies with significantly longer dendritic processes and larger cell bodies than non-stimulated controls. Taken together, the experimental evidence shows that the application of an electrical stimulation designed based on retinal development can be implemented to direct and enhance retinal differentiation of mRPCs, suggesting a role for biomimetic electrical stimulation in directing progenitor cells toward neural fates.

  12. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection

    PubMed Central

    Gorman, Jacob V.; Starbeck-Miller, Gabriel; Pham, Nhat-Long L.; Traver, Geri L.; Rothman, Paul B.; Harty, John T.; Colgan, John D.

    2014-01-01

    Tim-3 is a surface molecule expressed throughout the immune system that can mediate both stimulatory and inhibitory effects. Previous studies have provided evidence that Tim-3 functions to enforce CD8 T cell exhaustion, a dysfunctional state associated with chronic stimulation. In contrast, the role of Tim-3 in the regulation of CD8 T cell responses to acute and transient stimulation remains undefined. To address this knowledge gap, we examined how Tim-3 affects CD8 T cell responses to acute Listeria monocytogenes (LM) infection. Analysis of wild-type (WT) mice infected with LM revealed that Tim-3 was transiently expressed by activated CD8 T cells and was associated primarily with acquisition of an effector phenotype. Comparison of responses to LM by WT and Tim-3 KO mice showed that the absence of Tim-3 significantly reduced the magnitudes of both primary and secondary CD8 T cell responses, which correlated with decreased IFN-γ production and degranulation by Tim-3 KO cells stimulated with peptide antigen ex vivo. To address the T cell-intrinsic role of Tim-3, we analyzed responses to LM infection by WT and Tim-3 KO TCR-transgenic CD8 T cells following adoptive transfer into a shared WT host. In this setting, the accumulation of CD8 T cells and the generation of cytokine-producing cells were significantly reduced by the lack of Tim-3, demonstrating that this molecule has a direct effect on CD8 T cell function. Combined, our results suggest that Tim-3 can mediate a stimulatory effect on CD8 T cell responses to an acute infection. PMID:24567532

  13. Direct Carbon Fuel Cell System Utilizing Solid Carbonaceous Fuels

    SciTech Connect

    Turgut Gur

    2010-04-30

    This 1-year project has achieved most of its objective and successfully demonstrated the viability of the fluidized bed direct carbon fuel cell (FB-DCFC) approach under development by Direct Carbon technologies, LLC, that utilizes solid carbonaceous fuels for power generation. This unique electrochemical technology offers high conversion efficiencies, produces proportionately less CO{sub 2} in capture-ready form, and does not consume or require water for gasification. FB-DCFC employs a specialized solid oxide fuel cell (SOFC) arrangement coupled to a Boudouard gasifier where the solid fuel particles are fluidized and reacted by the anode recycle gas CO{sub 2}. The resulting CO is electrochemically oxidized at the anode. Anode supported SOFC structures employed a porous Ni cermet anode layer, a dense yttria stabilized zirconia membrane, and a mixed conducting porous perovskite cathode film. Several kinds of untreated solid fuels (carbon and coal) were tested in bench scale FBDCFC prototypes for electrochemical performance and stability testing. Single cells of tubular geometry with active areas up to 24 cm{sup 2} were fabricated. The cells achieved high power densities up to 450 mW/cm{sup 2} at 850 C using a low sulfur Alaska coal char. This represents the highest power density reported in the open literature for coal based DCFC. Similarly, power densities up to 175 mW/cm{sup 2} at 850 C were demonstrated with carbon. Electrical conversion efficiencies for coal char were experimentally determined to be 48%. Long-term stability of cell performance was measured under galvanostatic conditions for 375 hours in CO with no degradation whatsoever, indicating that carbon deposition (or coking) does not pose any problems. Similar cell stability results were obtained in coal char tested for 24 hours under galvanostatic conditions with no sign of sulfur poisoning. Moreover, a 50-cell planar stack targeted for 1 kW output was fabricated and tested in 95% CO (balance CO{sub 2

  14. Evidence for 'silicon' within the cell walls of suspension-cultured rice cells.

    PubMed

    He, Congwu; Wang, Lijun; Liu, Jian; Liu, Xin; Li, Xiuli; Ma, Jie; Lin, Yongjun; Xu, Fangsen

    2013-11-01

    Despite the ubiquity and beneficial role of silicon (Si) in plant biology, structural and chemical mechanisms operating at the single-cell level have not been extensively studied. To obtain insights regarding the effect of Si on individual cells, we cultivated suspended rice (Oryza sativa) cells in the absence and presence of Si and analyzed single cells using a combination of physical techniques including atomic force microscopy (AFM). Si is naturally present as a constituent of the cell walls, where it is firmly bound to the cell wall matrix rather than occurring within intra- or extracellular silica deposition, as determined by using inductively coupled plasma mass spectrometry (ICP-MS) and X-ray photoelectron spectroscopy (XPS). This species of Si, linked with the cell wall matrix, improves the structural stability of cell walls during their expansion and subsequent cell division. Maintaining cell shape is thereby enhanced, which may be crucial for the function and survival of cells. This study provides further evidence that organosilicon is present in plant cell walls, which broadens our understanding of the chemical nature of 'anomalous Si' in plant biology.

  15. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    PubMed

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  16. Direct demonstration of murine thymus-dependent cell surface endogenous immunoglobin.

    PubMed Central

    Szenberg, A; Marchalonis, J J; Warner, N L

    1977-01-01

    Antisera raised in mammals to murine immunoglobulin (Ig) do not detect surface Ig on thymus-dependent (T) lymphoma cells as assessed by immunofluorescence analysis. In contrast, chicken antibodies, produced against the (Fab)2 fragment of normal mouse IgG and purified by binding to and elution from IgG-Sepharose 4B, give strong indirect fluorescence with murine T cells and cultured T lymphoma cells. The surface Ig caps, is shed, and reappears, indicating that it is of endogenous origin. Nonlymphoid tumor cells of various myeloid types do not bind this reagent, even though they bear avid Fc receptors. The capacity of chicken antibodies to bind to both bone-marrow-dependent and T cell lymphomas was abolished by adsorption with myeloma-derived kappa chains coupled to Sepharose. The kappa antigenic determinant recognized by the chicken antibodies may thus be different from that seen by mammalian antibodies, and the degree of exposure of Ig on the T lymphoma surface might also affect ease of detectability with these reagents. These data provide direct evidence that T lymphocytes and T lymphoma cells express and synthesize a surface Ig containing determinants that at least 'crossreact with bone-marrow-cell-derived kappa chains. Images PMID:405673

  17. Directionally Solidified Biopolymer Scaffolds: Mechanical Properties and Endothelial Cell Responses

    PubMed Central

    Meghri, Nichols W.; Donius, Amalie E.; Riblett, Benjamin W.; Martin, Elizabeth J.; Clyne, Alisa Morss; Wegst, Ulrike G.K.

    2011-01-01

    Vascularization is a primary challenge in tissue engineering. To achieve it in a tissue scaffold, an environment with the appropriate structural, mechanical, and biochemical cues must be provided enabling endothelial cells to direct blood vessel growth. While biochemical stimuli such as growth factors can be added through the scaffold material, the culture medium, or both, a well-designed tissue engineering scaffold is required to provide the necessary local structural and mechanical cues. As chitosan is a well-known carrier for biochemical stimuli, the focus of this study was on structure-property correlations, to evaluate the effects of composition and processing conditions on the three-dimensional architecture and properties of freeze-cast scaffolds; to establish whether freeze-cast scaffolds are promising candidates as constructs promoting vascularization; and to conduct initial tissue culture studies with endothelial cells on flat substrates of identical compositions as those of the scaffolds to test whether these are biocompatible and promote cell attachment and proliferation. PMID:21544225

  18. Directionally solidified biopolymer scaffolds: Mechanical properties and endothelial cell responses

    NASA Astrophysics Data System (ADS)

    Meghri, Nicholas W.; Donius, Amalie E.; Riblett, Benjamin W.; Martin, Elizabeth J.; Clyne, Alisa Morss; Wegst, Ulrike G. K.

    2010-07-01

    Vascularization is a primary challenge in tissue engineering. To achieve it in a tissue scaffold, an environment with the appropriate structural, mechanical, and biochemical cues must be provided enabling endothelial cells to direct blood vessel growth. While biochemical stimuli such as growth factors can be added through the scaffold material, the culture medium, or both, a well-designed tissue engineering scaffold is required to provide the necessary local structural and mechanical cues. As chitosan is a well-known carrier for biochemical stimuli, the focus of this study was on structure-property correlations, to evaluate the effects of composition and processing conditions on the three-dimensional architecture and properties of freeze-cast scaffolds; to establish whether freeze-east scaffolds are promising candidates as constructs promoting vascularization; and to conduct initial tissue culture studies with endothelial cells on flat substrates of identical compositions as those of the scaffolds to test whether these are biocompatible and promote cell attachment and proliferation.

  19. Directionally Solidified Biopolymer Scaffolds: Mechanical Properties and Endothelial Cell Responses.

    PubMed

    Meghri, Nichols W; Donius, Amalie E; Riblett, Benjamin W; Martin, Elizabeth J; Clyne, Alisa Morss; Wegst, Ulrike G K

    2010-07-01

    Vascularization is a primary challenge in tissue engineering. To achieve it in a tissue scaffold, an environment with the appropriate structural, mechanical, and biochemical cues must be provided enabling endothelial cells to direct blood vessel growth. While biochemical stimuli such as growth factors can be added through the scaffold material, the culture medium, or both, a well-designed tissue engineering scaffold is required to provide the necessary local structural and mechanical cues. As chitosan is a well-known carrier for biochemical stimuli, the focus of this study was on structure-property correlations, to evaluate the effects of composition and processing conditions on the three-dimensional architecture and properties of freeze-cast scaffolds; to establish whether freeze-cast scaffolds are promising candidates as constructs promoting vascularization; and to conduct initial tissue culture studies with endothelial cells on flat substrates of identical compositions as those of the scaffolds to test whether these are biocompatible and promote cell attachment and proliferation.

  20. A microfluidic direct formate fuel cell on paper.

    PubMed

    Copenhaver, Thomas S; Purohit, Krutarth H; Domalaon, Kryls; Pham, Linda; Burgess, Brianna J; Manorothkul, Natalie; Galvan, Vicente; Sotez, Samantha; Gomez, Frank A; Haan, John L

    2015-08-01

    We describe the first direct formate fuel cell on a paper microfluidic platform. In traditional membrane-less microfluidic fuel cells (MFCs), external pumping consumes power produced by the fuel cell in order to maintain co-laminar flow of the anode stream and oxidant stream to prevent mixing. However, in paper microfluidics, capillary action drives flow while minimizing stream mixing. In this work, we demonstrate a paper MFC that uses formate and hydrogen peroxide as the anode fuel and cathode oxidant, respectively. Using these materials we achieve a maximum power density of nearly 2.5 mW/mg Pd. In a series configuration, our MFC achieves an open circuit voltage just over 1 V, and in a parallel configuration, short circuit of 20 mA absolute current. We also demonstrate that the MFC does not require continuous flow of fuel and oxidant to produce power. We found that we can pre-saturate the materials on the paper, stop the electrolyte flow, and still produce approximately 0.5 V for 15 min. This type of paper MFC has potential applications in point-of-care diagnostic devices and other electrochemical sensors.

  1. Studies on an ultrasonic atomization feed direct methanol fuel cell.

    PubMed

    Wu, Chaoqun; Liu, Linghao; Tang, Kai; Chen, Tao

    2017-01-01

    Direct methanol fuel cell (DMFC) is promising as an energy conversion device for the replacement of conventional chemical cell in future, owing to its convenient fuel storage, high energy density and low working temperature. The development of DMFC technology is currently limited by catalyst poison and methanol crossover. To alleviate the methanol crossover, a novel fuel supply system based on ultrasonic atomization is proposed. Experimental investigations on this fuel supply system to evaluate methanol permeation rates, open circuit voltages (OCVs) and polarization curves under a series of conditions have been carried out and reported in this paper. In comparison with the traditional liquid feed DMFC system, it can be found that the methanol crossover under the ultrasonic atomization feed system was significantly reduced because the DMFC reaches a large stable OCV value. Moreover, the polarization performance does not vary significantly with the liquid feed style. Therefore, the cell fed by ultrasonic atomization can be operated with a high concentration methanol to improve the energy density of DMFC. Under the supply condition of relatively high concentration methanol such as 4M and 8M, the maximum power density fed by ultrasonic atomization is higher than liquid by 6.05% and 12.94% respectively.

  2. SHAPE SELECTIVE NANOCATALYSTS FOR DIRECT METHANOL FUEL CELL APPLICATIONS

    SciTech Connect

    Murph, S.

    2012-09-12

    While gold and platinum have long been recognized for their beauty and value, researchers at the Savannah River National Laboratory (SRNL) are working on the nano-level to use these elements for creative solutions to our nation's energy and security needs. Multiinterdisciplinary teams consisting of chemists, materials scientists, physicists, computational scientists, and engineers are exploring unchartered territories with shape-selective nanocatalysts for the development of novel, cost effective and environmentally friendly energy solutions to meet global energy needs. This nanotechnology is vital, particularly as it relates to fuel cells.SRNL researchers have taken process, chemical, and materials discoveries and translated them for technological solution and deployment. The group has developed state-of-the art shape-selective core-shell-alloy-type gold-platinum nanostructures with outstanding catalytic capabilities that address many of the shortcomings of the Direct Methanol Fuel Cell (DMFC). The newly developed nanostructures not only busted the performance of the platinum catalyst, but also reduced the material cost and overall weight of the fuel cell.

  3. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia of the Lung (DIPNECH): Current Best Evidence.

    PubMed

    Wirtschafter, Eric; Walts, Ann E; Liu, Sandy T; Marchevsky, Alberto M

    2015-10-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.

  4. Biodegradation of benzidine based azodyes Direct red and Direct blue by the immobilized cells of Pseudomonas fluorescens D41.

    PubMed

    Puvaneswari, N; Muthukrishnan, J; Gunasekaran, P

    2002-10-01

    Benzidine based azodyes are proven carcinogens, mutagens and have been linked to bladder cancer of human beings and laboratory animals. The textile and dyestuff manufacturing industry are the two major sources that released azodyes in their effluents. The dye, Direct blue contains two carcinogenic compounds namely benzidine (BZ), 4-amino biphenyl (4-ABP), while the dye Direct red has benzidine (BZ). Among 40 isolates of Pseudomonas fluorescens screened, one isolate designated as D41 was found to be capable of extensively degrading the dyes Direct blue and Direct red. Immobilized cells of P. fluorescens D41 efficiently degraded Direct red (82%) and Direct blue (71%) in the presence of glucose.

  5. Direct Differentiation of Human Pluripotent Stem Cells into Haploid Spermatogenic Cells

    PubMed Central

    Easley, Charles A.; Phillips, Bart T.; McGuire, Megan M.; Barringer, Jennifer M.; Valli, Hanna; Hermann, Brian P.; Simerly, Calvin R.; Rajkovic, Aleksander; Miki, Toshio; Orwig, Kyle E.; Schatten, Gerald P.

    2013-01-01

    Summary Human embryonic (hESCs) and induced pluripotent stem cells (hiPSCs) have been shown to differentiate into primordial germ cells (PGCs) but not into spermatogonia nor haploid spermatocytes or spermatids. Here we show that hESCs and hiPSCs differentiate directly into advanced male germ cell lineages including post-meiotic, spermatid-like cells in vitro without genetic manipulation. Furthermore, our procedure mirrors spermatogenesis in vivo by differentiating pluripotent stem cells into UTF1, PLZF and CDH1-positive spermatogonia-like cells, HIWI and HILI-positive spermatocyte-like cells, and haploid cells expressing acrosin, transition protein 1 and protamine 1, proteins found uniquely in either spermatids and/or sperm. These spermatids show uniparental genomic imprints similar to human sperm on two loci: H19 and IGF2. These results demonstrate that male pluripotent stem cells have the capability to directly differentiate into advanced germ cell lineages and may represent a novel strategy for studying spermatogenesis in vitro. PMID:22921399

  6. Engineering the human pluripotent stem cell microenvironment to direct cell fate.

    PubMed

    Hazeltine, Laurie B; Selekman, Joshua A; Palecek, Sean P

    2013-11-15

    Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, offer a potential cell source for research, drug screening, and regenerative medicine applications due to their unique ability to self-renew or differentiate to any somatic cell type. Before the full potential of hPSCs can be realized, robust protocols must be developed to direct their fate. Cell fate decisions are based on components of the surrounding microenvironment, including soluble factors, substrate or extracellular matrix, cell-cell interactions, mechanical forces, and 2D or 3D architecture. Depending on their spatio-temporal context, these components can signal hPSCs to either self-renew or differentiate to cell types of the ectoderm, mesoderm, or endoderm. Researchers working at the interface of engineering and biology have identified various factors which can affect hPSC fate, often based on lessons from embryonic development, and they have utilized this information to design in vitro niches which can reproducibly direct hPSC fate. This review highlights culture systems that have been engineered to promote self-renewal or differentiation of hPSCs, with a focus on studies that have elucidated the contributions of specific microenvironmental cues in the context of those culture systems. We propose the use of microsystem technologies for high-throughput screening of spatial-temporal presentation of cues, as this has been demonstrated to be a powerful approach for differentiating hPSCs to desired cell types.

  7. Human metapneumovirus Induces Reorganization of the Actin Cytoskeleton for Direct Cell-to-Cell Spread

    PubMed Central

    El Najjar, Farah; Cifuentes-Muñoz, Nicolás; Zhu, Haining; Buchholz, Ursula J.; Moncman, Carole L.; Dutch, Rebecca Ellis

    2016-01-01

    Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. In contrast, inhibition of actin polymerization or alterations to Rho GTPase signaling pathways significantly decreased cell-to-cell spread. Furthermore, viral proteins and viral RNA were detected in intercellular extensions, suggesting direct transfer of viral genetic material to new target cells. While roles for paramyxovirus matrix and fusion proteins in membrane deformation have been previously demonstrated, we show that the HMPV phosphoprotein extensively co-localized with actin and induced formation of cellular extensions when transiently expressed, supporting a new model in which a paramyxovirus phosphoprotein is a key player in assembly and spread. Our results reveal a novel mechanism for HMPV direct cell-to-cell spread and provide insights into dissemination of respiratory viruses. PMID:27683250

  8. Directing cell migration and organization via nanocrater-patterned cell-repellent interfaces

    NASA Astrophysics Data System (ADS)

    Jeon, Hojeong; Koo, Sangmo; Reese, Willie Mae; Loskill, Peter; Grigoropoulos, Costas P.; Healy, Kevin E.

    2015-09-01

    Although adhesive interactions between cells and nanostructured interfaces have been studied extensively, there is a paucity of data on how nanostructured interfaces repel cells by directing cell migration and cell-colony organization. Here, by using multiphoton ablation lithography to pattern surfaces with nanoscale craters of various aspect ratios and pitches, we show that the surfaces altered the cells’ focal-adhesion size and distribution, thus affecting cell morphology, migration and ultimately localization. We also show that nanocrater pitch can disrupt the formation of mature focal adhesions to favour the migration of cells towards higher-pitched regions, which present increased planar area for the formation of stable focal adhesions. Moreover, by designing surfaces with variable pitch but constant nanocrater dimensions, we were able to create circular and striped cellular patterns. Our surface-patterning approach, which does not involve chemical treatments and can be applied to various materials, represents a simple method to control cell behaviour on surfaces.

  9. Evidence of asymmetric cell division and centrosome inheritance in human neuroblastoma cells.

    PubMed

    Izumi, Hideki; Kaneko, Yasuhiko

    2012-10-30

    Asymmetric cell division (ACD) is believed to be a physiological event that occurs during development and tissue homeostasis in a large variety of organisms. ACD produces two unequal daughter cells, one of which resembles a multipotent stem and/or progenitor cell, whereas the other has potential for differentiation. Although recent studies have shown that the balance between self-renewal and differentiation potentials is precisely controlled and that alterations in the balance may lead to tumorigenesis in Drosophila neuroblasts, it is largely unknown whether human cancer cells directly show ACD in an evolutionarily conserved manner. Here, we show that the conserved polarity/spindle protein NuMA is preferentially localized to one side of the cell cortex during cell division, generating unequal inheritance of fate-altering molecules in human neuroblastoma cell lines. We also show that the cells with a single copy of MYCN showed significantly higher percentages of ACD than those with MYCN amplification. Moreover, suppression of MYCN in MYCN-amplified cells caused ACD, whereas expression of MYCN in MYCN-nonamplified cells enhanced symmetric cell division. Furthermore, we demonstrate that centrosome inheritance follows a definite rule in ACD: The daughter centrosome with younger mother centriole is inherited to the daughter cell with NuMA preferentially localized to the cell cortex, whereas the mother centrosome with the older mother centriole migrates to the other daughter cell. Thus, the mechanisms of cell division of ACD or symmetric cell division and centrosome inheritance are recapitulated in human cancer cells, and these findings may facilitate studies on cancer stem cells.

  10. The interplay between sleep and emotion regulation: conceptual framework empirical evidence and future directions.

    PubMed

    Gruber, Reut; Cassoff, Jamie

    2014-11-01

    Emotions are biologically-based responses that help an organism meet challenges and opportunities, and involve changes in subjective experience, behavior, and physiology. Emotions arise when something important to us is at stake. Although many factors have been associated with healthy emotional regulation, the role of sleep in this process has been largely ignored. Recent studies, however, have begun to delineate how sleep critically affects emotional functioning. Nighttime sleep affects daytime mood, emotional reactivity and the capacity to regulate positive and negative emotions; conversely, daytime experiences affect sleep. Hence, there is a complex interplay between sleep and emotional regulation. The objective of this article is to examine this interplay in adults. This objective is addressed by utilizing a framework that identifies key aspects of the relationship between sleep and emotion. We propose that the connectivity between the emotional centers of the brain--the prefontal cortex and the amygdala--is in part dependent on the homeostatic sleep system such that connectivity between these brain networks is higher when rested and lower when sleep deprived. High connectivity drives more efficient executive functioning, while a disconnect leads to poor executive functioning capacity including emotional reactivity and impulsivity. The cognitive effects of the homeostatic system are couple with the mood regulation effects of the circadian system together dictating the degree to which one experiences emotional regulation or dysregulation. Further, the affective brain systems of individuals with clinical symptomology and/or pathology are suggested to be more vulnerable to homeostatic pressure and circadian lows or misalignment resulting in increased affective clinical symptomology. We review empirical evidence that supports this framework and explore the implications of this framework. Finally, we describe future directions for this type of work.

  11. Direct phylogenetic evidence for lateral transfer of elongation factor-like gene.

    PubMed

    Kamikawa, Ryoma; Inagaki, Yuji; Sako, Yoshihiko

    2008-05-13

    Genes encoding elongation factor-like (EFL) proteins, which show high similarity to elongation factor-1alpha (EF-1alpha), have been found in phylogenetically distantly related eukaryotes. The sporadic distribution of "EFL-containing" lineages within "EF-1alpha-containing" lineages indirectly, but strongly, suggests lateral gene transfer as the principal driving force in EFL evolution. However, one of the most critical aspects in the above hypothesis, the donor lineages in any putative cases of lateral EFL gene transfer, remained unclear. In this study, we provide direct evidence for lateral transfer of an EFL gene through the analyses of 10 diatom EFL genes. All diatom EFL homologues tightly clustered in phylogenetic analyses, suggesting acquisition of the exogenous EFL gene early in diatom evolution. Our survey additionally identified Thalassiosira pseudonana as a eukaryote bearing EF-1alpha and EFL genes and secondary EFL gene loss in Phaeodactylum tricornutum, the complete genome of which encodes only the EF-1alpha gene. Most importantly, the EFL phylogeny recovered a robust grouping of homologues from diatoms, the cercozoan Bigelowiella natans, and the foraminifer Planoglabratella opecularis, with the diatoms nested within the Bigelowiella plus Planoglabratella (Rhizaria) grouping. The particular relationships recovered are further consistent with two characteristic sequence motifs. The best explanation of our data analyses is an EFL gene transfer from a foraminifer to a diatom, the first case in which the donor-recipient relationship was clarified. Finally, based on a reverse transcriptase quantitative PCR assay and the genome information of Thalassiosira and Phaeodactylum, we propose the loss of elongation factor function in Thalassiosira EF-1alpha.

  12. Evidence for Cryptic Speciation in Directly Transmitted Gyrodactylid Parasites of Trinidadian Guppies

    PubMed Central

    Xavier, Raquel; Faria, Patricia J.; Paladini, Giuseppe; van Oosterhout, Cock; Johnson, Mireille; Cable, Jo

    2015-01-01

    Cryptic species complexes are common among parasites, which tend to have large populations and are subject to rapid evolution. Such complexes may arise through host-parasite co-evolution and/or host switching. For parasites that reproduce directly on their host, there might be increased opportunities for sympatric speciation, either by exploiting different hosts or different micro-habitats within the same host. The genus Gyrodactylus is a specious group of viviparous monogeneans. These ectoparasites transfer between teleosts during social contact and cause significant host mortality. Their impact on the guppy (Poecilia reticulata), an iconic evolutionary and ecological model species, is well established and yet the population genetics and phylogenetics of these parasites remains understudied. Using mtDNA sequencing of the host and its parasites, we provide evidence of cryptic speciation in Gyrodactylus bullatarudis, G. poeciliae and G. turnbulli. For the COII gene, genetic divergence of lineages within each parasite species ranged between 5.7 and 17.2%, which is typical of the divergence observed between described species in this genus. Different lineages of G. turnbulli and G. poeciliae appear geographically isolated, which could imply allopatric speciation. In addition, for G. poeciliae, co-evolution with a different host species cannot be discarded due to its host range. This parasite was originally described on P. caucana, but for the first time here it is also recorded on the guppy. The two cryptic lineages of G. bullatarudis showed considerable geographic overlap. G. bullatarudis has a known wide host range and it can also utilize a killifish (Anablepsoides hartii) as a temporary host. This killifish is capable of migrating overland and it could act as a transmission vector between otherwise isolated populations. Additional genetic markers are needed to confirm the presence of these cryptic Gyrodactylus species complexes, potentially leading to more in

  13. Direct evidence for a Coulombic phase in monopole-suppressed SU(2) lattice gauge theory

    NASA Astrophysics Data System (ADS)

    Grady, Michael

    2013-11-01

    Further evidence is presented for the existence of a non-confining phase at weak coupling in SU(2) lattice gauge theory. Using Monte Carlo simulations with the standard Wilson action, gauge-invariant SO(3)-Z2 monopoles, which are strong-coupling lattice artifacts, have been seen to undergo a percolation transition exactly at the phase transition previously seen using Coulomb gauge methods, with an infinite lattice critical point near β=3.2. The theory with both Z2 vortices and monopoles and SO(3)-Z2 monopoles eliminated is simulated in the strong-coupling (β=0) limit on lattices up to 604. Here, as in the high-β phase of the Wilson-action theory, finite size scaling shows it spontaneously breaks the remnant symmetry left over after Coulomb gauge fixing. Such a symmetry breaking precludes the potential from having a linear term. The monopole restriction appears to prevent the transition to a confining phase at any β. Direct measurement of the instantaneous Coulomb potential shows a Coulombic form with moderately running coupling possibly approaching an infrared fixed point of α˜1.4. The Coulomb potential is measured to 50 lattice spacings and 2 fm. A short-distance fit to the 2-loop perturbative potential is used to set the scale. High precision at such long distances is made possible through the use of open boundary conditions, which was previously found to cut random and systematic errors of the Coulomb gauge fixing procedure dramatically. The Coulomb potential agrees with the gauge-invariant interquark potential measured with smeared Wilson loops on periodic lattices as far as the latter can be practically measured with similar statistics data.

  14. Direct phylogenetic evidence for lateral transfer of elongation factor-like gene

    PubMed Central

    Kamikawa, Ryoma; Inagaki, Yuji; Sako, Yoshihiko

    2008-01-01

    Genes encoding elongation factor-like (EFL) proteins, which show high similarity to elongation factor-1α (EF-1α), have been found in phylogenetically distantly related eukaryotes. The sporadic distribution of “EFL-containing” lineages within “EF-1α-containing” lineages indirectly, but strongly, suggests lateral gene transfer as the principal driving force in EFL evolution. However, one of the most critical aspects in the above hypothesis, the donor lineages in any putative cases of lateral EFL gene transfer, remained unclear. In this study, we provide direct evidence for lateral transfer of an EFL gene through the analyses of 10 diatom EFL genes. All diatom EFL homologues tightly clustered in phylogenetic analyses, suggesting acquisition of the exogenous EFL gene early in diatom evolution. Our survey additionally identified Thalassiosira pseudonana as a eukaryote bearing EF-1α and EFL genes and secondary EFL gene loss in Phaeodactylum tricornutum, the complete genome of which encodes only the EF-1α gene. Most importantly, the EFL phylogeny recovered a robust grouping of homologues from diatoms, the cercozoan Bigelowiella natans, and the foraminifer Planoglabratella opecularis, with the diatoms nested within the Bigelowiella plus Planoglabratella (Rhizaria) grouping. The particular relationships recovered are further consistent with two characteristic sequence motifs. The best explanation of our data analyses is an EFL gene transfer from a foraminifer to a diatom, the first case in which the donor–recipient relationship was clarified. Finally, based on a reverse transcriptase quantitative PCR assay and the genome information of Thalassiosira and Phaeodactylum, we propose the loss of elongation factor function in Thalassiosira EF-1α. PMID:18458344

  15. No Evidence That RFamide-Related Peptide 3 Directly Modulates LH Secretion in the Ewe.

    PubMed

    Decourt, C; Anger, K; Robert, V; Lomet, D; Bartzen-Sprauer, J; Caraty, A; Dufourny, L; Anderson, G; Beltramo, M

    2016-04-01

    The neuropeptide RFamide-related peptide 3 (RFRP-3) has been implicated in the control of gonadotropin secretion in both birds and mammals. However, in mammals, depending on species, sex and photoperiod, inhibitory, excitatory, or no effect of RFRP-3 on the plasma concentration of LH has been reported. In the ewe, treatment with RFRP-3 either reduced LH concentration or had no effect, and treatment with an RFRP-3 receptor antagonist (ie, RF9) resulted in increased concentration of plasma LH. To clarify these conflicting results in the present study, a set of experiments was performed in ewes. Multiple iv injections of RFRP-3 (6 × 50 μg) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 μg) or an injection (250, 500, or 1000 μg) followed by a 4-hour perfusion (250, 500, or 1000 μg · h(-1)) of RFRP-3 had no effect on the LH pulse induced by kisspeptin (6.5 μg). In ovariectomized, estrogen-replaced ewes, the LH surge induced by estradiol benzoate was not modified by a 24-hour perfusion of RFRP-3 (500 μg h(-1)). Finally, although treatment with RF9 induced a robust release of LH, treatment with a more selective RFRP-3 receptor antagonist, GJ14, resulted in no evident increase of LH. In contrast to the inhibitory effect previously suggested, our data are more consistent with the concept that RFRP-3 has no direct effect on LH secretion in ewes and that RF9 effect on LH release is likely not RFRP-3 receptor mediated. Hence, RFRP-3 probably has a minor role on the control of LH secretion in the ewe.

  16. First evidence of pep solar neutrinos by direct detection in Borexino.

    PubMed

    Bellini, G; Benziger, J; Bick, D; Bonetti, S; Bonfini, G; Bravo, D; Buizza Avanzini, M; Caccianiga, B; Cadonati, L; Calaprice, F; Carraro, C; Cavalcante, P; Chavarria, A; Chepurnov, A; D'Angelo, D; Davini, S; Derbin, A; Etenko, A; Fomenko, K; Franco, D; Galbiati, C; Gazzana, S; Ghiano, C; Giammarchi, M; Goeger-Neff, M; Goretti, A; Grandi, L; Guardincerri, E; Hardy, S; Ianni, Aldo; Ianni, Andrea; Korablev, D; Korga, G; Koshio, Y; Kryn, D; Laubenstein, M; Lewke, T; Litvinovich, E; Loer, B; Lombardi, F; Lombardi, P; Ludhova, L; Machulin, I; Manecki, S; Maneschg, W; Manuzio, G; Meindl, Q; Meroni, E; Miramonti, L; Misiaszek, M; Montanari, D; Mosteiro, P; Muratova, V; Oberauer, L; Obolensky, M; Ortica, F; Otis, K; Pallavicini, M; Papp, L; Perasso, L; Perasso, S; Pocar, A; Quirk, J; Raghavan, R S; Ranucci, G; Razeto, A; Re, A; Romani, A; Sabelnikov, A; Saldanha, R; Salvo, C; Schönert, S; Simgen, H; Skorokhvatov, M; Smirnov, O; Sotnikov, A; Sukhotin, S; Suvorov, Y; Tartaglia, R; Testera, G; Vignaud, D; Vogelaar, R B; von Feilitzsch, F; Winter, J; Wojcik, M; Wright, A; Wurm, M; Xu, J; Zaimidoroga, O; Zavatarelli, S; Zuzel, G

    2012-02-03

    We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6{stat}±0.3{syst}  counts/(day·100  ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of <7.9  counts/(day·100  ton) (95% C.L.). The absence of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved by adopting data analysis techniques for the rejection of cosmogenic {11}C, the dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×10{8}  cm{-2} s^{-1} and <7.7×10{8}  cm{-2} s{-1} (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

  17. Donor human milk for preterm infants: current evidence and research directions.

    PubMed

    Arslanoglu, Sertac; Corpeleijn, Willemijn; Moro, Guido; Braegger, Christian; Campoy, Cristina; Colomb, Virginie; Decsi, Tamas; Domellöf, Magnus; Fewtrell, Mary; Hojsak, Iva; Mihatsch, Walter; Mølgaard, Christian; Shamir, Raanan; Turck, Dominique; van Goudoever, Johannes

    2013-10-01

    The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

  18. Direct Evidence for an Enhancement of Helium in Giant Stars in Omega Centauri

    NASA Astrophysics Data System (ADS)

    Dupree, A. K.; Strader, Jay; Smith, Graeme H.

    2011-02-01

    The double main sequence identified in the globular cluster Omega Centauri has been interpreted using isochrones to indicate a large variation in the abundance of helium. If true, a helium enhancement carries strong implications for the chemical and stellar evolutionary history of this cluster. However, only indirect measures currently support this conjecture. We report the discovery of a variation in the line strength of the near-infrared He I 10830 Å transition in 12 similar red giants in Omega Centauri observed with PHOENIX on Gemini-S. Abundances of these stars derived from Magellan/MIKE spectra taken at the Las Campanas Observatory show that the helium transition is not detected in the most metal-poor population ([Fe/H] < -1.8), yet is present in the majority of stars with [Fe/H] >= -1.8. These observations give the first direct evidence for an enhancement of helium in Omega Centauri. The appearance of helium appears better correlated with increased [Al/Fe] and [Na/Fe] abundances than as a function of [Fe/H], giving observational support to the presence of high-temperature H burning in a prior generation of stars. Data presented herein were obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the Science and Technology Facilities Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência e Tecnologia (Brazil), and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina). This paper also includes spectra gathered with the 6.5 m Magellan Telescope/CLAY located at Las Campanas Observatory, Chile.

  19. Future treatment directions for HPV-associated head and neck cancer based on radiobiological rationale and current clinical evidence.

    PubMed

    Marcu, Loredana G

    2016-07-01

    A relatively new entity of head and neck squamous cell carcinoma located in the oropharynx and associated to the human papillomavirus (HPV) is on the rise. This cancer represents a distinct entity from the non-HPV tumours, holds different biological characteristics and responds differently to treatment. An outcome analysis of locoregionally-advanced oropharyngeal versus non-oropharyngeal cancers treated with chemo-radiotherapy revealed a statistically significant improvement for oropharyngeal cancers, which are thought to be due to their HPV-association. Consequently, more attention is paid to HPV-related head and neck cancers, given that HPV status serves as prognostic marker in oropharyngeal cancer patients. Yet, HPV positivity is a simplistic approach for risk stratification, thus more robust biomarkers are needed to fulfil this task. Despite differences in clinical response, HPV-related oral cancers undergo similar therapy to their non-HPV counterparts. This review discusses future treatment directions for HPV-related oropharyngeal cancers based on radiobiological rationale and current clinical evidence.

  20. Evidence for Direct Control of Virulence and Defense Gene Circuits by the Pseudomonas aeruginosa Quorum Sensing Regulator, MvfR

    PubMed Central

    Maura, Damien; Hazan, Ronen; Kitao, Tomoe; Ballok, Alicia E.; Rahme, Laurence G.

    2016-01-01

    Pseudomonas aeruginosa defies eradication by antibiotics and is responsible for acute and chronic human infections due to a wide variety of virulence factors. Currently, it is believed that MvfR (PqsR) controls the expression of many of these factors indirectly via the pqs and phnAB operons. Here we provide strong evidence that MvfR may also bind and directly regulate the expression of additional 35 loci across the P. aeruginosa genome, including major regulators and virulence factors, such as the quorum sensing (QS) regulators lasR and rhlR, and genes involved in protein secretion, translation, and response to oxidative stress. We show that these anti-oxidant systems, AhpC-F, AhpB-TrxB2 and Dps, are critical for P. aeruginosa survival to reactive oxygen species and antibiotic tolerance. Considering that MvfR regulated compounds generate reactive oxygen species, this indicates a tightly regulated QS self-defense anti-poisoning system. These findings also challenge the current hierarchical regulation model of P. aeruginosa QS systems by revealing new interconnections between them that suggest a circular model. Moreover, they uncover a novel role for MvfR in self-defense that favors antibiotic tolerance and cell survival, further demonstrating MvfR as a highly desirable anti-virulence target. PMID:27678057

  1. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    SciTech Connect

    Li, Wen-Zhong; Ai, Zhi-Ying; Wang, Zhi-Wei; Chen, Lin-Lin; Guo, Ze-Kun; Zhang, Yong

    2015-09-25

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.

  2. Bi-directional electrical characterisation of microbial fuel cell.

    PubMed

    Degrenne, N; Ledezma, P; Bevilacqua, P; Buret, F; Allard, B; Greenman, J; Ieropoulos, I A

    2013-01-01

    The electrical performance of microbial fuel cells in steady-state is usually investigated by standard characterisation methods that reveal many important parameters e.g. maximum power. This paper introduces a novel "bi-directional" method to study how the acquisition parameters (i.e. sweep rate and sweep regime) can influence measurements and consequently performance estimations. The investigation exhibited considerable differences (hysteresis) between the forward and backward characterisation regimes, indicating a difficulty to reach steady-state under certain conditions. Moreover, it is found that fast sweep rates (time-step of 2 min) can lead to an overestimation of the short-circuit currents, while prolonged operation with high external loads leads to maximum power overestimation and extended conditioning at high currents can result in its underestimation.

  3. Thin Film Catalyst Layers for Direct Methanol Fuel Cells

    NASA Technical Reports Server (NTRS)

    Witham, C. K.; Chun, W.; Ruiz, R.; Valdez, T. I.; Narayanan, S. R.

    2000-01-01

    One of the primary obstacles to the widespread use of the direct methanol fuel cell (DMFC) is the high cost of the catalyst. Therefore, reducing the catalyst loading well below the current level of 8-12 mg/cm 2 would be important to commercialization. The current methods for preparation of catalyst layers consisting of catalyst, ionomer and sometimes a hydrophobic additive are applied by either painting, spraying, decal transfer or screen printing processes. Sputter deposition is a coating technique widely used in manufacturing and therefore particularly attractive. In this study we have begun to explore sputtering as a method for catalyst deposition. Present experiments focus on Pt-Ru catalyst layers for the anode.

  4. Surface modification of carbon fuels for direct carbon fuel cells

    NASA Astrophysics Data System (ADS)

    Li, Xiang; Zhu, Zhonghua; Chen, Jiuling; De Marco, Roland; Dicks, Andrew; Bradley, John; Lu, Gaoqing

    The direct carbon fuel cell (DCFC) is a promising power-generation device that has much higher efficiency (80%) and less emissions than conventional coal-fired power plants. Two commercial carbons (activated carbon and carbon black) pre-treated with HNO 3, HCl or air plasma are tested in a DCFC. The correlation between the surface properties and electrochemical performance of the carbon fuels is explored. The HNO 3-treated carbon fuels have the highest electrochemical reactivity in the DCFC due to the largest degree of surface oxygen functional groups. The overall effect on changing the electrochemical reactivity of carbon fuels is in the order HNO 3 > air plasma ≈ HCl. Product gas analysis indicates that complete oxidation of carbon to CO 2 can be achieved at 600-700 °C.

  5. Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

    NASA Technical Reports Server (NTRS)

    Jorgensen, Charles C.

    1997-01-01

    A Dynamic Cell Structure (DCS) Neural Network was developed which learns topology representing networks (TRNS) of F-15 aircraft aerodynamic stability and control derivatives. The network is integrated into a direct adaptive tracking controller. The combination produces a robust adaptive architecture capable of handling multiple accident and off- nominal flight scenarios. This paper describes the DCS network and modifications to the parameter estimation procedure. The work represents one step towards an integrated real-time reconfiguration control architecture for rapid prototyping of new aircraft designs. Performance was evaluated using three off-line benchmarks and on-line nonlinear Virtual Reality simulation. Flight control was evaluated under scenarios including differential stabilator lock, soft sensor failure, control and stability derivative variations, and air turbulence.

  6. Maintenance of the enteric stem cell niche by bacterial lipopolysaccharides? Evidence and perspectives.

    PubMed

    Schuster, Anne; Klotz, Markus; Schwab, Tanja; Di Liddo, Rosa; Bertalot, Thomas; Schrenk, Sandra; Martin, Monika; Nguyen, The Duy; Nguyen, Thi Nha Quyen; Gries, Manuela; Faßbender, Klaus; Conconi, Maria Teresa; Parnigotto, Pier Paolo; Schäfer, Karl-Herbert

    2014-07-01

    The enteric nervous system (ENS) has to respond to continuously changing microenvironmental challenges within the gut and is therefore dependent on a neural stem cell niche to keep the ENS functional throughout life. In this study, we hypothesize that this stem cell niche is also affected during inflammation and therefore investigated lipopolysaccharides (LPS) effects on enteric neural stem/progenitor cells (NSPCs). NSPCs were derived from the ENS and cultured under the influence of different LPS concentrations. LPS effects upon proliferation and differentiation of enteric NSPC cultures were assessed using immunochemistry, flow cytometry, western blot, Multiplex ELISA and real-time PCR. LPS enhances the proliferation of enteric NSPCs in a dose-dependent manner. It delays and modifies the differentiation of these cells. The expression of the LPS receptor toll-like receptor 4 on NSPCs could be demonstrated. Moreover, LPS induces the secretion of several cytokines. Flow cytometry data gives evidence for individual subgroups within the NSPC population. ENS-derived NSPCs respond to LPS in maintaining at least partially their stem cell character. In the case of inflammatory disease or trauma where the liberation and exposure to LPS will be increased, the expansion of NSPCs could be a first step towards regeneration of the ENS. The reduced and altered differentiation, as well as the induction of cytokine signalling, demonstrates that the stem cell niche may take part in the LPS-transmitted inflammatory processes in a direct and defined way.

  7. Low direct cytotoxicity of nabumetone on gastric mucosal cells.

    PubMed

    Arai, Yasuhiro; Tanaka, Ken-Ichiro; Ushijima, Hironori; Tomisato, Wataru; Tsutsumi, Shinji; Aburaya, Mayuko; Hoshino, Tatsuya; Yokomizo, Kazumi; Suzuki, Keitarou; Katsu, Takashi; Tsuchiya, Tomofusa; Mizushima, Tohru

    2005-09-01

    Prodrugs of non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for clinical purposes because they are not harmful to the gastrointestinal mucosa. We recently showed that NSAIDs have direct cytotoxicity in NSAID-induced gastric lesions. We show here that under conditions where the NSAIDs indomethacin and celecoxib clearly induce cell death, an NSAID prodrug, nabumetone, and its active metabolite 6-methoxy-2-naphthylacetic acid (6MNA), did not have such effects. Moreover, nabumetone and 6MNA exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We recently reported that when an orally administered NSAID was used in combination with a low dose of intravenously administered indomethacin, the severity of gastric lesions produced in rats depended on the cytotoxicity of the orally administered NSAID. Using a similar protocol, we show here that gastric lesions were produced when the orally administered NSAID was celecoxib, but not when nabumetone was used. We thus propose that the low direct cytotoxicity of nabumetone observed in vitro is maintained in vivo, and that the use of nabumetone does not harm the gastric mucosa.

  8. Erythropoietin protects against diabetes through direct effects on pancreatic β cells

    PubMed Central

    Choi, Diana; Schroer, Stephanie A.; Lu, Shun Yan; Wang, Linyuan; Wu, Xiaohong; Liu, Yunfeng; Zhang, Yi; Gaisano, Herbert Y.; Wagner, Kay-Uwe; Wu, Hong; Retnakaran, Ravi

    2010-01-01

    A common feature among all forms of diabetes mellitus is a functional β-cell mass insufficient to maintain euglycemia; therefore, the promotion of β-cell growth and survival is a fundamental goal for diabetes prevention and treatment. Evidence has suggested that erythropoietin (EPO) exerts cytoprotective effects on nonerythroid cells. However, the influence of EPO on pancreatic β cells and diabetes has not been evaluated to date. In this study, we report that recombinant human EPO treatment can protect against diabetes development in streptozotocin-induced and db/db mouse models of type 1 and type 2 diabetes, respectively. EPO exerts antiapoptotic, proliferative, antiinflammatory, and angiogenic effects within the islets. Using β-cell–specific EPO receptor and JAK2 knockout mice, we show that these effects of EPO result from direct biological effects on β cells and that JAK2 is an essential intracellular mediator. Thus, promotion of EPO signaling in β cells may be a novel therapeutic strategy for diabetes prevention and treatment. PMID:21149549

  9. Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing

    SciTech Connect

    Fletcher, James H.; Cox, Philip; Harrington, William J; Campbell, Joseph L

    2013-09-03

    ABSTRACT Project Title: Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing PROJECT OBJECTIVE The objective of the project was to advance portable fuel cell system technology towards the commercial targets of power density, energy density and lifetime. These targets were laid out in the DOE’s R&D roadmap to develop an advanced direct methanol fuel cell power supply that meets commercial entry requirements. Such a power supply will enable mobile computers to operate non-stop, unplugged from the wall power outlet, by using the high energy density of methanol fuel contained in a replaceable fuel cartridge. Specifically this project focused on balance-of-plant component integration and miniaturization, as well as extensive component, subassembly and integrated system durability and validation testing. This design has resulted in a pre-production power supply design and a prototype that meet the rigorous demands of consumer electronic applications. PROJECT TASKS The proposed work plan was designed to meet the project objectives, which corresponded directly with the objectives outlined in the Funding Opportunity Announcement: To engineer the fuel cell balance-of-plant and packaging to meet the needs of consumer electronic systems, specifically at power levels required for mobile computing. UNF used existing balance-of-plant component technologies developed under its current US Army CERDEC project, as well as a previous DOE project completed by PolyFuel, to further refine them to both miniaturize and integrate their functionality to increase the system power density and energy density. Benefits of UNF’s novel passive water recycling MEA (membrane electrode assembly) and the simplified system architecture it enabled formed the foundation of the design approach. The package design was hardened to address orientation independence, shock, vibration, and environmental requirements. Fuel cartridge and fuel subsystems were improved to ensure effective fuel

  10. Evidence of dysregulation of dendritic cells in primary HIV infection

    PubMed Central

    Sabado, Rachel Lubong; O'Brien, Meagan; Subedi, Abhignya; Qin, Li; Hu, Nan; Taylor, Elizabeth; Dibben, Oliver; Stacey, Andrea; Fellay, Jacques; Shianna, Kevin V.; Siegal, Frederick; Shodell, Michael; Shah, Kokila; Larsson, Marie; Lifson, Jeffrey; Nadas, Arthur; Marmor, Michael; Hutt, Richard; Margolis, David; Garmon, Donald; Markowitz, Martin; Valentine, Fred; Borrow, Persephone

    2010-01-01

    Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV in-fection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation. PMID:20693428

  11. Evidence of dysregulation of dendritic cells in primary HIV infection.

    PubMed

    Sabado, Rachel Lubong; O'Brien, Meagan; Subedi, Abhignya; Qin, Li; Hu, Nan; Taylor, Elizabeth; Dibben, Oliver; Stacey, Andrea; Fellay, Jacques; Shianna, Kevin V; Siegal, Frederick; Shodell, Michael; Shah, Kokila; Larsson, Marie; Lifson, Jeffrey; Nadas, Arthur; Marmor, Michael; Hutt, Richard; Margolis, David; Garmon, Donald; Markowitz, Martin; Valentine, Fred; Borrow, Persephone; Bhardwaj, Nina

    2010-11-11

    Myeloid and plasmacytoid dendritic cells (DCs) are important mediators of both innate and adaptive immunity against pathogens such as HIV. During the course of HIV infection, blood DC numbers fall substantially. In the present study, we sought to determine how early in HIV infection the reduction occurs and whether the remaining DC subsets maintain functional capacity. We find that both myeloid DC and plasmacytoid DC levels decline very early during acute HIV infection. Despite the initial reduction in numbers, those DCs that remain in circulation retain their function and are able to stimulate allogeneic T-cell responses, and up-regulate maturation markers plus produce cytokines/chemokines in response to stimulation with TLR7/8 agonists. Notably, DCs from HIV-infected subjects produced significantly higher levels of cytokines/chemokines in response to stimulation with TLR7/8 agonists than DCs from uninfected controls. Further examination of gene expression profiles indicated in vivo activation, either directly or indirectly, of DCs during HIV infection. Taken together, our data demonstrate that despite the reduction in circulating DC numbers, those that remain in the blood display hyperfunctionality and implicates a possible role for DCs in promoting chronic immune activation.

  12. Fabric-based alkaline direct formate microfluidic fuel cells.

    PubMed

    Domalaon, Kryls; Tang, Catherine; Mendez, Alex; Bernal, Franky; Purohit, Krutarth; Pham, Linda; Haan, John; Gomez, Frank A

    2017-01-12

    Fabric-based microfluidic fuel cells (MFCs) serve as a novel, cost-efficient alternative to traditional FCs and batteries, since fluids naturally travel across fabric via capillary action, eliminating the need for an external pump and lowering production and operation costs. Building on previous research with Y-shaped paper-based MFCs, fabric-based MFCs mitigate fragility and durability issues caused by long periods of fuel immersion. In this study, we describe a microfluidic fabric-based direct formate fuel cell, with 5 M potassium formate and 30% hydrogen peroxide as the anode fuel and cathode oxidant, respectively. Using a two-strip, stacked design, the optimized parameters include the type of encasement, the barrier, and the fabric type. Surface contact of the fabric and laminate sheet expedited flow and respective chemical reactions. The maximum current (22.83 mA/cm(2) ) and power (4.40 mW/cm(2) ) densities achieved with a 65% cotton/35% polyester blend material are a respective 8.7% and 32% higher than previous studies with Y-shaped paper-based MFCs. In series configuration, the MFCs generate sufficient energy to power a handheld calculator, a thermometer, and a spectrum of light-emitting diodes.

  13. Improved Flow-Field Structures for Direct Methanol Fuel Cells

    SciTech Connect

    Gurau, Bogdan

    2013-05-31

    The direct methanol fuel cell (DMFC) is ideal if high energy-density liquid fuels are required. Liquid fuels have advantages over compressed hydrogen including higher energy density and ease of handling. Although state-of-the-art DMFCs exhibit manageable degradation rates, excessive fuel crossover diminishes system energy and power density. Although use of dilute methanol mitigates crossover, the concomitant lowering of the gross fuel energy density (GFED) demands a complex balance-of-plant (BOP) that includes higher flow rates, external exhaust recirculation, etc. An alternative approach is redesign of the fuel delivery system to accommodate concentrated methanol. NuVant Systems Inc. (NuVant) will maximize the GFED by design and assembly of a DMFC that uses near neat methanol. The approach is to tune the diffusion of highly concentrated methanol (to the anode catalytic layer) to the back-diffusion of water formed at the cathode (i.e. in situ generation of dilute methanol at the anode layer). Crossover will be minimized without compromising the GFED by innovative integration of the anode flow-field and the diffusion layer. The integrated flow-field-diffusion-layers (IFDLs) will widen the current and potential DMFC operating ranges and enable the use of cathodes optimized for hydrogen-air fuel cells.

  14. Towards operating direct methanol fuel cells with highly concentrated fuel

    NASA Astrophysics Data System (ADS)

    Zhao, T. S.; Yang, W. W.; Chen, R.; Wu, Q. X.

    A significant advantage of direct methanol fuel cells (DMFCs) is the high specific energy of the liquid fuel, making it particularly suitable for portable and mobile applications. Nevertheless, conventional DMFCs have to be operated with excessively diluted methanol solutions to limit methanol crossover and the detrimental consequences. Operation with diluted methanol solutions significantly reduces the specific energy of the power pack and thereby prevents it from competing with advanced batteries. In view of this fact, there exists a need to improve conventional DMFC system designs, including membrane electrode assemblies and the subsystems for supplying/removing reactants/products, so that both the cell performance and the specific energy can be simultaneously maximized. This article provides a comprehensive review of past efforts on the optimization of DMFC systems that operate with concentrated methanol. Based on the discussion of the key issues associated with transport of the reactants/products, the strategies to manage the supply/removal of the reactants/products in DMFC operating with highly concentrated methanol are identified. With these strategies, the possible approaches to achieving the goal of concentrated fuel operation are then proposed. Past efforts in the management of the reactants/products for implementing each of the approaches are also summarized and reviewed.

  15. Direct fuel cell - A high proficiency power generator for biofuels

    SciTech Connect

    Patel, P.S.; Steinfeld, G.; Baker, B.S.

    1994-12-31

    Conversion of renewable bio-based resources into energy offers significant benefits for our environment and domestic economic activity. It also improves national security by displacing fossil fuels. However, in the current economic environment, it is difficult for biofuel systems to compete with other fossil fuels. The biomass-fired power plants are typically smaller than 50 MW, lower in electrical efficiencies (<25%) and experience greater costs for handling and transporting the biomass. When combined with fuel cells such as the Direct Fuel Cell (DFC), biofuels can produce power more efficiently with negligible environmental impact. Agricultural and other waste biomass can be converted to ethanol or methane-rich biofuels for power generation use in the DFC. These DFC power plants are modular and factory assembled. Due to their electrochemical (non-combustion) conversion process, these plants are environmentally friendly, highly efficient and potentially cost effective, even in sizes as small as a few meagawatts. They can be sited closer to the source of the biomass to minimize handling and transportation costs. The high-grade waste heat available from DFC power plants makes them attractive in cogeneration applications for farming and rural communities. The DFC potentially opens up new markets for biofuels derived from wood, grains and other biomass waste products.

  16. A Direct Carbon Fuel Cell with a Molten Antimony Anode

    SciTech Connect

    Jayakumar, Abhimanyu; Kungas, Rainer; Roy, Sounak; Javadekar, Ashay; Buttrey, Douglas J.; Vohs, John M.; Gorte, Raymond J.

    2011-01-01

    The direct utilization of carbonaceous fuels is examined in a solid oxide fuel cell (SOFC) with a molten Sb anode at 973 K. It is demonstrated that the anode operates by oxidation of metallic Sb at the electrolyte interface, with the resulting Sb₂O₃ being reduced by the fuel in a separate step. Although the Nernst Potential for the Sb-Sb₂O₃ mixture is only 0.75 V, the electrode resistance associated with molten Sb is very low, approximately 0.06 Ωcm², so that power densities greater than 350 mW cm⁻² were achieved with an electrolyte-supported cell made from Sc-stabilized zirconia (ScSZ). Temperature programmed reaction measurements of Sb₂O₃ with sugar char, rice starch, carbon black, and graphite showed that the Sb₂O₃ is readily reduced by a range of carbonaceous solids at typical SOFC operating conditions. Finally, stable operation with a power density of 300 mW cm⁻² at a potential of 0.5 V is demonstrated for operation on sugar char.

  17. Improved Cathode Structure for a Direct Methanol Fuel Cell

    NASA Technical Reports Server (NTRS)

    Valdez, Thomas; Narayanan, Sekharipuram

    2005-01-01

    An improved cathode structure on a membrane/electrode assembly has been developed for a direct methanol fuel cell, in a continuing effort to realize practical power systems containing such fuel cells. This cathode structure is intended particularly to afford better cell performance at a low airflow rate. A membrane/electrode assembly of the type for which the improved cathode structure was developed (see Figure 1) is fabricated in a process that includes brush painting and spray coating of catalyst layers onto a polymer-electrolyte membrane and onto gas-diffusion backings that also act as current collectors. The aforementioned layers are then dried and hot-pressed together. When completed, the membrane/electrode assembly contains (1) an anode containing a fine metal black of Pt/Ru alloy, (2) a membrane made of Nafion 117 or equivalent (a perfluorosulfonic acid-based hydrophilic, proton-conducting ion-exchange polymer), (3) a cathode structure (in the present case, the improved cathode structure described below), and (4) the electrically conductive gas-diffusion backing layers, which are made of Toray 060(TradeMark)(or equivalent) carbon paper containing between 5 and 6 weight percent of poly(tetrafluoroethylene). The need for an improved cathode structure arises for the following reasons: In the design and operation of a fuel-cell power system, the airflow rate is a critical parameter that determines the overall efficiency, cell voltage, and power density. It is desirable to operate at a low airflow rate in order to obtain thermal and water balance and to minimize the size and mass of the system. The performances of membrane/electrode assemblies of prior design are limited at low airflow rates. Methanol crossover increases the required airflow rate. Hence, one way to reduce the required airflow rate is to reduce the effect of methanol crossover. Improvement of the cathode structure - in particular, addition of hydrophobic particles to the cathode - has been

  18. SWI/SNF-directed stem cell lineage specification: dynamic composition regulates specific stages of skeletal myogenesis

    PubMed Central

    Toto, Paula Coutinho; Puri, Pier Lorenzo; Albini, Sonia

    2016-01-01

    SWI/SNF chromatin-remodeling complexes are key regulators of the epigenetic modifications that determine whether stem cells maintain pluripotency or commit toward specific lineages through development and during postnatal life. Dynamic combinatorial assembly of multiple variants of SWI/SNF subunits is emerging as the major determinant of the functional versatility of SWI/SNF. Here, we summarize the current knowledge on the structural and functional properties of the alternative SWI/SNF complexes that direct stem cell fate toward skeletal muscle lineage and control distinct stages of skeletal myogenesis. In particular, we will refer to recent evidence pointing to the essential role of two SWI/SNF components not expressed in embryonic stem cells—the catalytic subunit BRM and the structural component BAF60C—whose induction in muscle progenitors coincides with the expansion of their transcriptional repertoire. PMID:27207468

  19. Direct glycerol fuel cell with polytetrafluoroethylene (PTFE) thin film separator

    DOE PAGES

    Benipal, Neeva; Qi, Ji; Gentile, Jacob C.; ...

    2017-01-04

    Here, anion-exchange membrane-based direct glycerol fuel cells (AEM-DGFCs) can yield high power density, however challenges exist in developing chemically stable AEMs. Here, we demonstrate a porous PTFE thin film, a well-known chemical, electro-chemical, and thermal robust material that can serve as a separator between anode and cathode, thus achieving high DGFC’s performance. A simple aqueous-phase reduction method was used to prepare carbon nanotube supported PdAg nanoparticles (PdAg/CNT) with an average particle size of 2.9 nm. A DGFC using a PTFE thin film without any further modification with PdAg/CNT anode catalyst exhibits a peak power density of 214.7 mW cm–2 atmore » 80 °C, about 22.6% lower than a DGFC using a state-of-the-art AEM. We report a 5.8% decrease and 11.1% decrease in cell voltage for a PTFE thin film and AEM; similarly, the cell voltage degradation rate decreases from 1.2 to 0.8 mV h–1 for PTFE thin film, while for AEM, it decreases from 9.6 to 3.0 mV h–1 over an 80 h durability test period. Transmission electron microscopy results indicate that the average particle size of PdAg/CNT increases from 2.9 to 3.7 nm after 80 h discharge; this suggests that PdAg particle growth may be the main reason for the performance drop.« less

  20. Novel APC-like properties of human NK cells directly regulate T cell activation

    PubMed Central

    Hanna, Jacob; Gonen-Gross, Tsufit; Fitchett, Jonathan; Rowe, Tony; Daniels, Mark; Arnon, Tal I.; Gazit, Roi; Joseph, Aviva; Schjetne, Karoline W.; Steinle, Alexander; Porgador, Angel; Mevorach, Dror; Goldman-Wohl, Debra; Yagel, Simcha; LaBarre, Michael J.; Buckner, Jane H.; Mandelboim, Ofer

    2004-01-01

    Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane–enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell–mediated cytotoxicity and specific ligand recognition by cell surface–activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell–activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV-infected uterine decidual samples, and from transporter-associated processing antigen 2–deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell–activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells. PMID:15578093

  1. Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

    SciTech Connect

    Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B. Palo Alto Veterans Administration Medical Center, CA ); Rubin, D.H. )

    1988-04-01

    Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 (VP3); 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time of 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated {sup 51}Cr, ({sup 14}C)choline, and ({sup 3}H)inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration.

  2. Evidence-Based Practice in the United States: Challenges, Progress, and Future Directions

    PubMed Central

    Correa-de-Araujo, Rosaly

    2016-01-01

    Scientific literature demonstrates that advances in evidence-based nursing have improved systems of care and women’s health outcomes. Experts agree that nurses worldwide can play a key role in building such evidence and working with interdisciplinary health care teams and systems to accelerate its implementation. PMID:26473771

  3. The direct effect of estrogen on cell viability and apoptosis in human gastric cancer cells.

    PubMed

    Qin, Jian; Liu, Min; Ding, Qianshan; Ji, Xiang; Hao, Yarong; Wu, Xiaomin; Xiong, Jie

    2014-10-01

    Epidemiology researches indicated that gastric cancer is a male-predominant disease; both expression level of estrogen and expression pattern of estrogen receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen on gastric cancer cells is still unclear. This study aimed to explore the direct effect of β-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were treated with a serial of concentrations of E2. The survival rates of both the cell lines were significantly reduced, and the reduction of viability was due to apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3 fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were reduced. Apoptosis was further confirmed by flow cytometry. The expression level of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both ERα and ERβ were expressed in these cell lines, and the result of bioinformatics analysis of gastric cancer from GEO datasets indicated that the expression levels of both ERα and ERβ were significantly higher in noncancerous gastric tissues than in gastric cancer tissues. Our research indicated that estrogen can reduce cell viability and promote apoptosis in gastric cancer cells directly; ERs expression level is associated with gastric cancer. Our research will help to understand the mechanism of gender disparity in gastric cancer.

  4. A Review of E-Learning in Canada: A Rough Sketch of the Evidence, Gaps and Promising Directions: A Commentary

    ERIC Educational Resources Information Center

    Kanuka, Heather

    2006-01-01

    The purpose of the "Review of E-Learning in Canada", conducted by Abrami and associates (which is referred to as "the team"), was to provide evidence and gaps on the topic of e-learning, and based on this data provide promising directions for e-learning. Funded by the Canadian Council on Learning, the stated objectives of the…

  5. A Review of e-Learning in Canada: A Rough Sketch of the Evidence, Gaps and Promising Directions

    ERIC Educational Resources Information Center

    Abrami, Philip C.; Bernard, Robert M.; Wade, Anne; Schmid, Richard F.; Borokhovski, Eugene; Tamim, Rana; Surkes, Michael; Lowerison, Gretchen; Zhang, Dai; Nicolaidou, Iolie; Newman, Sherry; Wozney, Lori; Peretiatkowicz, Anna

    2006-01-01

    This review provides a rough sketch of the evidence, gaps and promising directions in e-learning from 2000 onwards, with a particular focus on Canada. The authors searched a wide range of sources and document types to ensure that we represented, comprehensively, the arguments surrounding e-learning. Overall, there were 2,042 entries in their…

  6. Temperature structures in Galactic center clouds. Direct evidence for gas heating via turbulence

    NASA Astrophysics Data System (ADS)

    Immer, K.; Kauffmann, J.; Pillai, T.; Ginsburg, A.; Menten, K. M.

    2016-11-01

    The central molecular zone at the center of our Galaxy is the best template to study star formation processes under extreme conditions, similar to those in high-redshift galaxies. We observed on-the-fly maps of para-H2CO transitions at 218 GHz and 291 GHz towards seven Galactic center clouds. From the temperature-sensitive integrated intensity line ratios of H2CO(32,1 -22,0)/H2CO(30,3 -20,2) and H2CO(42,2 -32,1)/H2CO(40,4 -30,3) in combination with radiative transfer models, we produce gas temperature maps of our targets. These transitions are sensitive to gas with densities of 105 cm-3 and temperatures <150 K. The measured gas temperatures in our sources are all higher (>40 K) than their dust temperatures ( 25 K). Our targets have a complex velocity structure that requires a careful disentanglement of the different components. We produce temperature maps for each of the velocity components and show that the temperatures of the components differ, revealing temperature gradients in the clouds. Combining the temperature measurements with the integrated intensity line ratio of H2CO(40,4 -30,3)/H2CO(30,3 -20,2), we constrain the density of this warm gas to 104 -106 cm-3. We find a positive correlation between the line width of the main H2CO lines and the temperature of the gas, direct evidence for gas heating via turbulence. Our data is consistent with a turbulence heating model with a density of n = 105 cm-3. Integrated intensity maps of the H2CO lines (Figs. E.1-E.7), ratio and uncertainty maps (Figs. F.1-F.7), and temperature and uncertainty maps (Figs. H.1-H.7) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/595/A94

  7. Direct effects of music in non-auditory cells in culture.

    PubMed

    Lestard, Nathalia Dos Reis; Valente, Raphael C; Lopes, Anibal G; Capella, Márcia A M

    2013-01-01

    The biological effects of electromagnetic waves are widely studied, especially due to their harmful effects, such as radiation-induced cancer and to their application in diagnosis and therapy. However, the biological effects of sound, another physical agent to which we are frequently exposed have been considerably disregarded by the scientific community. Although a number of studies suggest that emotions evoked by music may be useful in medical care, alleviating stress and nociception in patients undergoing surgical procedures as well as in cancer and burned patients, little is known about the mechanisms by which these effects occur. It is generally accepted that the mechanosensory hair cells in the ear transduce the sound-induced mechanical vibrations into neural impulses, which are interpreted by the brain and evoke the emotional effects. In the last decade; however, several studies suggest that the response to music is even more complex. Moreover, recent evidence comes out that cell types other than auditory hair cells could response to audible sound. However, what is actually sensed by the hair cells, and possible by other cells in our organism, are physical differences in fluid pressure induced by the sound waves. Therefore, there is no reasonable impediment for any cell type of our body to respond to a pure sound or to music. Hence, the aim of the present study was to evaluate the response of a human breast cancer cell line, MCF7, to music. The results' obtained suggest that music can alter cellular morpho-functional parameters, such as cell size and granularity in cultured cells. Moreover, our results suggest for the 1 st time that music can directly interfere with hormone binding to their targets, suggesting that music or audible sounds could modulate physiological and pathophysiological processes.

  8. Endothelial cells direct mesenchymal stem cells toward a smooth muscle cell fate.

    PubMed

    Lin, Cho-Hao; Lilly, Brenda

    2014-11-01

    Under defined conditions, mesenchymal stem cells can differentiate into unique cell types, making them attractive candidates for cell-based disease therapies. Ischemic diseases would greatly benefit from treatments that include the formation of new blood vessels from mesenchymal stem cells. However, blood vessels are complex structures composed of endothelial cells and smooth muscle cells, and their assembly and function in a diseased environment is reliant upon joining with the pre-existing vasculature. Although endothelial cell/smooth muscle cell interactions are well known, how endothelial cells may influence mesenchymal stem cells and facilitate their differentiation has not been defined. Therefore, we sought to explore how endothelial cells might drive mesenchymal stem cells toward a smooth muscle fate. Our data show that cocultured endothelial cells induce smooth muscle cell differentiation in mesenchymal stem cells. Endothelial cells can promote a contractile phenotype, reduce proliferation, and enhance collagen synthesis and secretion. Our data show that Notch signaling is essential for endothelial cell-dependent differentiation, and this differentiation pathway is largely independent of growth factor signaling mechanisms.

  9. Direct fuel cell power plants: the final steps to commercialization

    NASA Astrophysics Data System (ADS)

    Glenn, Donald R.

    Since the last paper presented at the Second Grove Fuel Cell Symposium, the Energy Research Corporation (ERC) has established two commercial subsidiaries, become a publically-held firm, expanded its facilities and has moved the direct fuel cell (DFC) technology and systems significantly closer to commercial readiness. The subsidiaries, the Fuel Cell Engineering Corporation (FCE) and Fuel Cell Manufacturing Corporation (FCMC) are perfecting their respective roles in the company's strategy to commercialize its DFC technology. FCE is the prime contractor for the Santa Clara Demonstration and is establishing the needed marketing, sales, engineering, and servicing functions. FCMC in addition to producing the stacks and stack modules for the Santa Clara demonstration plant is now upgrading its production capability and product yields, and retooling for the final stack scale-up for the commercial unit. ERC has built and operated the tallest and largest capacities-to-date carbonate fuel cell stacks as well as numerous short stacks. While most of these units were tested at ERC's Danbury, Connecticut (USA) R&D Center, others have been evaluated at other domestic and overseas facilities using a variety of fuels. ERC has supplied stacks to Elkraft and MTU for tests with natural gas, and RWE in Germany where coal-derived gas were used. Additional stack test activities have been performed by MELCO and Sanyo in Japan. Information from some of these activities is protected by ERC's license arrangements with these firms. However, permission for limited data releases will be requested to provide the Grove Conference with up-to-date results. Arguably the most dramatic demonstration of carbonate fuel cells in the utility-scale, 2 MW power plant demonstration unit, located in the City of Santa Clara, California. Construction of the unit's balance-of-plant (BOP) has been completed and the installed equipment has been operationally checked. Two of the four DFC stack sub-modules, each

  10. Translating research for evidence-based public health: key concepts and future directions.

    PubMed

    Rychetnik, Lucie; Bauman, Adrian; Laws, Rachel; King, Lesley; Rissel, Chris; Nutbeam, Don; Colagiuri, Stephen; Caterson, Ian

    2012-12-01

    Applying research to guide evidence-based practice is an ongoing and significant challenge for public health. Developments in the emerging field of 'translation' have focused on different aspects of the problem, resulting in competing frameworks and terminology. In this paper the scope of 'translation' in public health is defined, and four related but conceptually different 'translation processes' that support evidence-based practice are outlined: (1) reviewing the transferability of evidence to new settings, (2) translation research, (3) knowledge translation, and (4) knowledge translation research. Finally, an integrated framework is presented to illustrate the relationship between these domains, and priority areas for further development and empirical research are identified.

  11. Extending Assertive Community Treatment to criminal justice settings: origins, current evidence, and future directions.

    PubMed

    Morrissey, Joseph; Meyer, Piper; Cuddeback, Gary

    2007-10-01

    This paper presents an overview of Assertive Community Treatment (ACT) as an evidence-based practice in mental health care. We then consider current evidence for FACT (ACT for forensic populations) and FICM (intensive case management for forensic populations) and the ways these models have been extended and adapted to serve mentally ill persons in a variety of criminal justice settings. The available evidence about the effectiveness of these models towards preventing recidivism among criminally-justice involved persons with mental illness is weak. We conclude with several suggestions for how the clinical model of FACT needs to be expanded to incorporate interventions aimed at reducing criminal behavior and recidivism.

  12. A goal-directed spatial navigation model using forward trajectory planning based on grid cells.

    PubMed

    Erdem, Uğur M; Hasselmo, Michael

    2012-03-01

    A goal-directed navigation model is proposed based on forward linear look-ahead probe of trajectories in a network of head direction cells, grid cells, place cells and prefrontal cortex (PFC) cells. The model allows selection of new goal-directed trajectories. In a novel environment, the virtual rat incrementally creates a map composed of place cells and PFC cells by random exploration. After exploration, the rat retrieves memory of the goal location, picks its next movement direction by forward linear look-ahead probe of trajectories in several candidate directions while stationary in one location, and finds the one activating PFC cells with the highest reward signal. Each probe direction involves activation of a static pattern of head direction cells to drive an interference model of grid cells to update their phases in a specific direction. The updating of grid cell spiking drives place cells along the probed look-ahead trajectory similar to the forward replay during waking seen in place cell recordings. Directions are probed until the look-ahead trajectory activates the reward signal and the corresponding direction is used to guide goal-finding behavior. We report simulation results in several mazes with and without barriers. Navigation with barriers requires a PFC map topology based on the temporal vicinity of visited place cells and a reward signal diffusion process. The interaction of the forward linear look-ahead trajectory probes with the reward diffusion allows discovery of never-before experienced shortcuts towards a goal location.

  13. Left–right asymmetric cell intercalation drives directional collective cell movement in epithelial morphogenesis

    PubMed Central

    Sato, Katsuhiko; Hiraiwa, Tetsuya; Maekawa, Emi; Isomura, Ayako; Shibata, Tatsuo; Kuranaga, Erina

    2015-01-01

    Morphogenetic epithelial movement occurs during embryogenesis and drives complex tissue formation. However, how epithelial cells coordinate their unidirectional movement while maintaining epithelial integrity is unclear. Here we propose a novel mechanism for collective epithelial cell movement based on Drosophila genitalia rotation, in which epithelial tissue rotates clockwise around the genitalia. We found that this cell movement occurs autonomously and requires myosin II. The moving cells exhibit repeated left–right-biased junction remodelling, while maintaining adhesion with their neighbours, in association with a polarized myosin II distribution. Reducing myosinID, known to cause counter-clockwise epithelial-tissue movement, reverses the myosin II distribution. Numerical simulations revealed that a left–right asymmetry in cell intercalation is sufficient to induce unidirectional cellular movement. The cellular movement direction is also associated with planar cell-shape chirality. These findings support a model in which left–right asymmetric cell intercalation within an epithelial sheet drives collective cellular movement in the same direction. PMID:26656655

  14. Transduction of the scorpion toxin maurocalcine into cells. Evidence that the toxin crosses the plasma membrane

    PubMed Central

    Estève, Eric; Mabrouk, Kamel; Dupuis, Alain; Smida-Rezgui, Sophia; Altafaj, Xavier; Grunwald, Didier; Platel, Jean-Claude; Andreotti, Nicolas; Marty, Isabelle; Sabatier, Jean-Marc; Ronjat, Michel; De Waard, Michel

    2005-01-01

    Maurocalcine (MCa) is a 33 amino acid residue peptide toxin isolated from the scorpion Scorpio maurus palmatus. External application of MCa to cultured myotubes is known to produce Ca2+ release from intracellular stores. MCa binds directly to the skeletal muscle isoform of the ryanodine receptor, an intracellular channel target of the endoplasmic reticulum, and induces long-lasting channel openings in a mode of smaller conductance. Here, we investigated the way MCa proceeds to cross biological membranes in order to reach its target. A biotinylated derivative of MCa was produced (MCab) and complexed with a fluorescent indicator (streptavidine-cyanine 3) in order to follow the cell penetration of the toxin. The toxin complex efficiently penetrated in various cell types without requiring metabolic energy (low temperature) or implicating an endocytosis mechanism. MCa appeared to share the same features as the so-called Cell-Penetrating Peptides (CPP). Our results provide evidence that MCa has the ability to act as a molecular carrier and to cross cell membranes in a rapid manner (1–2 min) making this toxin the first demonstrated example of a scorpion toxin that translocates into cells. PMID:15653689

  15. MiR-200c promotes bladder cancer cell migration and invasion by directly targeting RECK

    PubMed Central

    Cheng, Yidong; Zhang, Xiaolei; Li, Peng; Yang, Chengdi; Tang, Jinyuan; Deng, Xiaheng; Yang, Xiao; Tao, Jun; Lu, Qiang; Li, Pengchao

    2016-01-01

    Background Increasing evidence suggests that the dysregulation of certain microRNAs plays an important role in tumorigenesis and metastasis. MiR-200c exhibits a disordered expression in many tumors and presents dual roles in bladder cancer (BC). Therefore, the definite role of miR-200c in BC needs to be investigated further. Materials and methods Quantitative reverse transcription polymerase chain reaction was used to assess miR-200c expression. Cell invasion and migration were evaluated using wound healing and transwell assays. The luciferase reporter assay was used to identify the direct target of miR-200c. The expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK) in BC tissues and adjacent nontumor tissues, as well as in BC cell lines, was detected through quantitative reverse transcription polymerase chain reaction, Western blot assay, and immunohistochemistry. Results The miR-200c expression was significantly upregulated in the BC tissues compared with the adjacent nontumor tissues. The downregulation of miR-200c significantly inhibited cell migration and invasion in the BC cell lines. The luciferase reporter assay showed that RECK was a direct target of miR-200c. The knockdown of RECK in the BC cell lines treated with anti-miR-200c elevated the previously attenuated cell migration and invasion. Conclusion Our findings indicated that miR-200c functions as oncogenes in BC and may provide a novel therapeutic strategy for the treatment of BC. PMID:27574450

  16. Nano-Engineered Catalysts for Direct Methanol Fuel Cells

    NASA Technical Reports Server (NTRS)

    Myung, Nosang; Narayanan, Sekharipuram; Wiberg, Dean

    2008-01-01

    Nano-engineered catalysts, and a method of fabricating them, have been developed in a continuing effort to improve the performances of direct methanol fuel cells as candidate power sources to supplant primary and secondary batteries in a variety of portable electronic products. In order to realize the potential for high energy densities (as much as 1.5 W h/g) of direct methanol fuel cells, it will be necessary to optimize the chemical compositions and geometric configurations of catalyst layers and electrode structures. High performance can be achieved when catalyst particles and electrode structures have the necessary small feature sizes (typically of the order of nanometers), large surface areas, optimal metal compositions, high porosity, and hydrophobicity. The present method involves electrodeposition of one or more catalytic metal(s) or a catalytic-metal/polytetrafluoroethylene nanocomposite on an alumina nanotemplate. The alumina nanotemplate is then dissolved, leaving the desired metal or metal/polytetrafluoroethylene-composite catalyst layer. Unlike some prior methods of making fine metal catalysts, this method does not involve processing at elevated temperature; all processing can be done at room temperature. In addition, this method involves fewer steps and is more amenable to scaling up for mass production. Alumina nanotemplates are porous alumina membranes that have been fabricated, variously, by anodizing either pure aluminum or aluminum that has been deposited on silicon by electronbeam evaporation. The diameters of the pores (7 to 300 nm), areal densities of pores (as much as 7 x 10(exp 10)sq cm), and lengths of pores (up to about 100 nm) can be tailored by selection of fabrication conditions. In a given case, the catalytic metal, catalytic metal alloy, or catalytic metal/ polytetrafluoroethylene composite is electrodeposited in the pores of the alumina nanotemplate. The dimensions of the pores, together with the electrodeposition conditions

  17. Evidence-Based Interventions in School Psychology: State of the Art and Directions for the Future.

    ERIC Educational Resources Information Center

    Gutkin, Terry B.

    2002-01-01

    Presents an overview of this special journal issue, designed to provide a current snapshot of the accomplishments and controversies pertaining to evidence-based intervention in school psychology. (GCP)

  18. Computational modeling of a direct propane fuel cell

    NASA Astrophysics Data System (ADS)

    Khakdaman, H.; Bourgault, Y.; Ternan, M.

    2011-03-01

    The first two dimensional mathematical model of a complete direct propane fuel cell (DPFC) is described. The governing equations were solved using FreeFem software that uses finite element methods. Robin boundary conditions were used to couple the anode, membrane, and cathode sub-domains successfully. The model showed that a polytetrafluoroethylene membrane having its pores filled with zirconium phosphate (ZrP-PTFE), in a DPFC at 150 °C performed much the same as other electrolytes; Nafion, aqueous H3PO4, and H2SO4 doped polybenzimidazole, when they were used in DPFCs. One advantage of a ZrP-PTFE at 150 °C is that it operates without liquid phase water. As a result corrosion will be much less severe and it may be possible for non-precious metal catalysts to be used. Computational results showed that the thickness of the catalyst layer could be increased sufficiently so that the pressure drop between the reactant and product channels of the interdigitated flow fields is small. By increasing the width of the land and therefore the reactant's contact time with the catalyst it was possible to approach 100% propane conversion. Therefore fuel cell operation with a minimum concentration of propane in the product stream should be possible. Finally computations of the electrical potential in the ZrP phase, the electron flux in the Pt/C phase, and the overpotential in both the anode and cathode catalyst layers showed that serious errors in the model occurred because proton diffusion, caused by the proton concentration gradient, was neglected in the equation for the conservation of protons.

  19. Hippocampal place cell instability after lesions of the head direction cell network

    NASA Technical Reports Server (NTRS)

    Calton, Jeffrey L.; Stackman, Robert W.; Goodridge, Jeremy P.; Archey, William B.; Dudchenko, Paul A.; Taube, Jeffrey S.; Oman, C. M. (Principal Investigator)

    2003-01-01

    The occurrence of cells that encode spatial location (place cells) or head direction (HD cells) in the rat limbic system suggests that these cell types are important for spatial navigation. We sought to determine whether place fields of hippocampal CA1 place cells would be altered in animals receiving lesions of brain areas containing HD cells. Rats received bilateral lesions of anterodorsal thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell recording. Although place cells from lesioned animals did not differ from controls on many place-field characteristics, such as place-field size and infield firing rate, the signal was significantly degraded with respect to measures of outfield firing rate, spatial coherence, and information content. Surprisingly, place cells from lesioned animals were more likely modulated by the directional heading of the animal. Rotation of the landmark cue showed that place fields from PoS-lesioned animals were not controlled by the cue and shifted unpredictably between sessions. Although fields from ADN-lesioned animals tended to have less landmark control than fields from control animals, this impairment was mild compared with cells recorded from PoS-lesioned animals. Removal of the prominent visual cue also led to instability of place-field representations in PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest that an intact HD system is not necessary for the maintenance of place fields, but lesions of brain areas that convey the HD signal can degrade this signal, and lesions of the PoS might lead to perceptual or mnemonic deficits, leading to place-field instability between sessions.

  20. Directed Induction of Functional Motor Neuron-Like Cells from Genetically Engineered Human Mesenchymal Stem Cells

    PubMed Central

    Park, Hwan-Woo; Cho, Jung-Sun; Park, Chul-Kyu; Jung, Sung Jun; Park, Chang-Hwan; Lee, Shin-Jae; Oh, Seog Bae; Park, Young-Seok; Chang, Mi-Sook

    2012-01-01

    Cell replacement using stem cells is a promising therapeutic approach to treat degenerative motor neuron (MN) disorders, such as amyotrophic lateral sclerosis and spinal cord injury. Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell source for autologous cell replacement therapy to treat nervous system injury due to their plasticity, low immunogenicity, and a lower risk of tumor formation than embryonic stem cells. However, hMSCs are inefficient with regards to differentiating into MN-like cells. To solve this limitation, we genetically engineered hMSCs to express MN-associated transcription factors, Olig2 and Hb9, and then treat the hMSCs expressing Olig2 and Hb9 with optimal MN induction medium (MNIM). This method of induction led to higher expression (>30% of total cells) of MN markers. Electrophysiological data revealed that the induced hMSCs had the excitable properties of neurons and were able to form functional connections with muscle fibers in vitro. Furthermore, when the induced hMSCs were transplanted into an injured organotypic rat spinal cord slice culture, an ex vivo model of spinal cord injury, they exhibited characteristics of MNs. The data strongly suggest that induced Olig2/Hb9-expressing hMSCs were clearly reprogrammed and directed toward a MN-like lineage. We propose that methods to induce Olig2 and Hb9, followed by further induction with MNIM have therapeutic potential for autologous cell replacement therapy to treat degenerative MN disorders. PMID:22496912

  1. Novel anode catalyst for direct methanol fuel cells.

    PubMed

    Basri, S; Kamarudin, S K; Daud, W R W; Yaakob, Z; Kadhum, A A H

    2014-01-01

    PtRu catalyst is a promising anodic catalyst for direct methanol fuel cells (DMFCs) but the slow reaction kinetics reduce the performance of DMFCs. Therefore, this study attempts to improve the performance of PtRu catalysts by adding nickel (Ni) and iron (Fe). Multiwalled carbon nanotubes (MWCNTs) are used to increase the active area of the catalyst and to improve the catalyst performance. Electrochemical analysis techniques, such as energy dispersive X-ray spectrometry (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS), are used to characterize the kinetic parameters of the hybrid catalyst. Cyclic voltammetry (CV) is used to investigate the effects of adding Fe and Ni to the catalyst on the reaction kinetics. Additionally, chronoamperometry (CA) tests were conducted to study the long-term performance of the catalyst for catalyzing the methanol oxidation reaction (MOR). The binding energies of the reactants and products are compared to determine the kinetics and potential surface energy for methanol oxidation. The FESEM analysis results indicate that well-dispersed nanoscale (2-5 nm) PtRu particles are formed on the MWCNTs. Finally, PtRuFeNi/MWCNT improves the reaction kinetics of anode catalysts for DMFCs and obtains a mass current of 31 A g(-1) catalyst.

  2. Novel Anode Catalyst for Direct Methanol Fuel Cells

    PubMed Central

    Basri, S.; Kamarudin, S. K.; Daud, W. R. W.; Yaakob, Z.; Kadhum, A. A. H.

    2014-01-01

    PtRu catalyst is a promising anodic catalyst for direct methanol fuel cells (DMFCs) but the slow reaction kinetics reduce the performance of DMFCs. Therefore, this study attempts to improve the performance of PtRu catalysts by adding nickel (Ni) and iron (Fe). Multiwalled carbon nanotubes (MWCNTs) are used to increase the active area of the catalyst and to improve the catalyst performance. Electrochemical analysis techniques, such as energy dispersive X-ray spectrometry (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS), are used to characterize the kinetic parameters of the hybrid catalyst. Cyclic voltammetry (CV) is used to investigate the effects of adding Fe and Ni to the catalyst on the reaction kinetics. Additionally, chronoamperometry (CA) tests were conducted to study the long-term performance of the catalyst for catalyzing the methanol oxidation reaction (MOR). The binding energies of the reactants and products are compared to determine the kinetics and potential surface energy for methanol oxidation. The FESEM analysis results indicate that well-dispersed nanoscale (2–5 nm) PtRu particles are formed on the MWCNTs. Finally, PtRuFeNi/MWCNT improves the reaction kinetics of anode catalysts for DMFCs and obtains a mass current of 31 A g−1 catalyst. PMID:24883406

  3. New Catalysts for Direct Methanol Oxidation Fuel Cells

    SciTech Connect

    Adzic, Radoslav

    1998-08-01

    A new class of efficient electrocatalytic materials based on platinum - metal oxide systems has been synthetized and characterized by several techniques. Best activity was found with NiWO{sub 4}-, CoWO{sub 4}-, and RuO{sub 2}- sr¡pported platinum catalysts. A very similar activity at room temperature was observed with the electrodes prepared with the catalyst obtained from International Fuel Cells Inc. for the same Pt loading. Surprisingly, the two tungstates per se show a small activity for methanol oxidation without any Pt loading. Synthesis of NiWO{sub 4} and CoWO{sub 4} were carried out by solid-state reactions. FTIR spectroscopy shows that the tungstates contain a certain amount of physically adsorbed water even after heating samples at 200{degrees}C. A direct relationship between the activity for methanol oxidation and the amount of adsorbed water on those oxides has been found. The Ru(0001) single crystal shows a very small activity for CO adsorption and oxidation, in contrast to the behavior of polycrystalline Ru. In situ extended x-ray absorption fine structure spectroscopy (EXAFS) and x-ray absorption near edge spectroscopy (XANES) showed that the OH adsorption on Ru in the Pt-Ru alloy appears to be the limiting step in methanol oxidation. This does not occur for Pt-RuO{SUB 2} electrocatalyst, which explains its advantages over the Pt-Ru alloys. The IFCC electrocatalyst has the properties of the Pt-Ru alloy.

  4. Modified SPEEK membranes for direct ethanol fuel cell

    NASA Astrophysics Data System (ADS)

    Maab, Husnul; Nunes, Suzana Pereira

    Membranes with low ethanol crossover were prepared aiming their application for direct ethanol fuel cell (DEFC). They were based on (1) sulfonated poly(ether ether ketone) (SPEEK) coated with carbon molecular sieves (CMS) and (2) on SPEEK/PI homogeneous blends. The membranes were characterized concerning their water and ethanol solution uptake, water and ethanol permeability in pervaporation experiments and their performance in DEFC tests. The ethanol permeabilities for the CMS-coated (180 nm and 400 nm thick layers) SPEEK were 8.5 and 3.1 × 10 -10 kg m s -1 m -2 and for the homogeneous SPEEK/PI blends membranes with 10, 20 and 30 wt.% of PI were 4.4, 1.0 and 0.4 × 10 -10 kg m s -1 m -2 respectively, which is 2- to 50-fold lower than that for plain SPEEK (19 × 10 -10 kg m s -1 m -2). Particularly the SPEEK/PI membranes had substantially better performance than Nafion 117 ® membranes in DEFC tests at 60 °C and 90 °C.

  5. An improved alkaline direct formate paper microfluidic fuel cell.

    PubMed

    Galvan, Vicente; Domalaon, Kryls; Tang, Catherine; Sotez, Samantha; Mendez, Alex; Jalali-Heravi, Mehdi; Purohit, Krutarth; Pham, Linda; Haan, John; Gomez, Frank A

    2016-02-01

    Paper-based microfluidic fuel cells (MFCs) are a potential replacement for traditional FCs and batteries due to their low cost, portability, and simplicity to operate. In MFCs, separate solutions of fuel and oxidant migrate through paper due to capillary action and laminar flow and, upon contact with each other and catalyst, produce electricity. In the present work, we describe an improved microfluidic paper-based direct formate FC (DFFC) employing formate and hydrogen peroxide as the anode fuel and cathode oxidant, respectively. The dimensions of the lateral column, current collectors, and cathode were optimized. A maximum power density of 2.53 mW/cm(2) was achieved with a DFFC of surface area 3.0 cm(2) , steel mesh as current collector, 5% carbon to paint mass ratio for cathode electrode and, 30% hydrogen peroxide. The longevity of the MFC's detailed herein is greater than eight hours with continuous flow of streams. In a series configuration, the MFCs generate sufficient energy to power light-emitting diodes and a handheld calculator.

  6. Item-Specific Encoding Produces an Additional Benefit of Directed Forgetting: Evidence from Intrusion Errors

    ERIC Educational Resources Information Center

    Sahakyan, Lili; Delaney, Peter F.

    2010-01-01

    List-method directed forgetting involves encoding 2 lists, between which half of the participants are told to forget List 1. When participants are free to study however they want, directed forgetting impairs List 1 recall and enhances List 2 recall in the forget group compared with a control remember group. In a large-scale experiment, the current…

  7. Are Consumer-Directed Home Care Beneficiaries Satisfied? Evidence from Washington State

    ERIC Educational Resources Information Center

    Wiener, Joshua M.; Anderson, Wayne L.; Khatutsky, Galina

    2007-01-01

    Purpose: This study analyzed the effect of consumer-directed versus agency-directed home care on satisfaction with paid personal assistance services among Medicaid beneficiaries in Washington State. Design and Methods: The study analyzed a survey of 513 Medicaid beneficiaries receiving home- and community-based services. As part of a larger study,…

  8. Gradient isolation of glial cells: evidence that flat epithelial cells are astroglial cell precursors.

    PubMed

    Meller, K

    1987-07-01

    Discontinuous gradients of metrizamide were used to separate the cell components of monolayers of primary cultures of embryonic rat brains. These primary cell cultures were of two types: long-term cultures (more than a year) of embryonic rat brain, which contained several glial cell types, and monolayers of cell cultures (several weeks old), which contained a complex population of cells, including neuronal elements. The gradient separation produces fractions of pure flat epithelial cells that are able to survive and proliferate. After a few days, all flat epithelial cells become confluent and show a positive reaction to glial fibrillary acidic protein (GFAP); this indicates that these cells astroglial precursor cells. Following their maintenance in vitro for several months, all cultures give rise to a pure population of astrocytes identified not only by their characteristic morphology, but also by their content of GFAP. It is proposed that the differentiation controls are dependent on cell interactions that are influenced by the composition of the cell population and/or the molecular growth and differentiation factors released by these cells into the medium.

  9. Direct Monitoring of Nucleotide Turnover in Human Cell Extracts and Cells by Fluorogenic ATP Analogs.

    PubMed

    Hacker, Stephan M; Buntz, Annette; Zumbusch, Andreas; Marx, Andreas

    2015-11-20

    Nucleotides containing adenosine play pivotal roles in every living cell. Adenosine triphosphate (ATP), for example, is the universal energy currency, and ATP-consuming processes also contribute to posttranslational protein modifications. Nevertheless, detecting the turnover of adenosine nucleotides in the complex setting of a cell remains challenging. Here, we demonstrate the use of fluorogenic analogs of ATP and adenosine tetraphosphate to study nucleotide hydrolysis in lysates of human cell lines and in intact human cells. We found that the adenosine triphosphate analog is completely stable in lysates of human cell lines, whereas the adenosine tetraphosphate analog is rapidly turned over. The observed activity in human cell lysates can be assigned to a single enzyme, namely, the human diadenosine tetraphosphate hydrolase NudT2. Since NudT2 has been shown to be a prognostic factor for breast cancer, the adenosine tetraphosphate analog might contribute to a better understanding of its involvement in cancerogenesis and allow the straightforward screening for inhibitors. Studying hydrolysis of the analogs in intact cells, we found that electroporation is a suitable method to deliver nucleotide analogs into the cytoplasm and show that high FRET efficiencies can be detected directly after internalization. Time-dependent experiments reveal that adenosine triphosphate and tetraphosphate analogs are both processed in the cellular environment. This study demonstrates that these nucleotide analogs indeed bear the potential to be powerful tools for the exploration of nucleotide turnover in the context of whole cells.

  10. Evidence for Direct Electron Transfer by a Gram-Positive Bacterium Isolated from a Microbial Fuel Cell▿†

    PubMed Central

    Wrighton, K. C.; Thrash, J. C.; Melnyk, R. A.; Bigi, J. P.; Byrne-Bailey, K. G.; Remis, J. P.; Schichnes, D.; Auer, M.; Chang, C. J.; Coates, J. D.

    2011-01-01

    Despite their importance in iron redox cycles and bioenergy production, the underlying physiological, genetic, and biochemical mechanisms of extracellular electron transfer by Gram-positive bacteria remain insufficiently understood. In this work, we investigated respiration by Thermincola potens strain JR, a Gram-positive isolate obtained from the anode surface of a microbial fuel cell, using insoluble electron acceptors. We found no evidence that soluble redox-active components were secreted into the surrounding medium on the basis of physiological experiments and cyclic voltammetry measurements. Confocal microscopy revealed highly stratified biofilms in which cells contacting the electrode surface were disproportionately viable relative to the rest of the biofilm. Furthermore, there was no correlation between biofilm thickness and power production, suggesting that cells in contact with the electrode were primarily responsible for current generation. These data, along with cryo-electron microscopy experiments, support contact-dependent electron transfer by T. potens strain JR from the cell membrane across the 37-nm cell envelope to the cell surface. Furthermore, we present physiological and genomic evidence that c-type cytochromes play a role in charge transfer across the Gram-positive bacterial cell envelope during metal reduction. PMID:21908627

  11. Nocturnal migratory songbirds adjust their travelling direction aloft: evidence from a radiotelemetry and radar study.

    PubMed

    Sjöberg, Sissel; Nilsson, Cecilia

    2015-06-01

    In order to fully understand the orientation behaviour of migrating birds, it is important to understand when birds set their travel direction. Departure directions of migratory passerines leaving stopover sites are often assumed to reflect the birds' intended travel directions, but this assumption has not been critically tested. We used data from an automated radiotelemetry system and a tracking radar at Falsterbo peninsula, Sweden, to compare the initial orientation of departing songbirds (recorded by radiotelemetry) with the orientation of songbird migrants in climbing and level flight (recorded by radar). We found that the track directions of birds at high altitudes and in level flight were more concentrated than the directions of departing birds and birds in climbing flight, which indicates that the birds adjust their travelling direction once aloft. This was further supported by a wide scatter of vanishing bearings in a subsample of radio-tracked birds that later passed an offshore radio receiver station 50 km southeast of Falsterbo. Track directions seemed to be more affected by winds in climbing compared with level flights, which may be explained by birds not starting to partially compensate for wind drift until they have reached cruising altitudes.

  12. Nocturnal migratory songbirds adjust their travelling direction aloft: evidence from a radiotelemetry and radar study

    PubMed Central

    Sjöberg, Sissel; Nilsson, Cecilia

    2015-01-01

    In order to fully understand the orientation behaviour of migrating birds, it is important to understand when birds set their travel direction. Departure directions of migratory passerines leaving stopover sites are often assumed to reflect the birds' intended travel directions, but this assumption has not been critically tested. We used data from an automated radiotelemetry system and a tracking radar at Falsterbo peninsula, Sweden, to compare the initial orientation of departing songbirds (recorded by radiotelemetry) with the orientation of songbird migrants in climbing and level flight (recorded by radar). We found that the track directions of birds at high altitudes and in level flight were more concentrated than the directions of departing birds and birds in climbing flight, which indicates that the birds adjust their travelling direction once aloft. This was further supported by a wide scatter of vanishing bearings in a subsample of radio-tracked birds that later passed an offshore radio receiver station 50 km southeast of Falsterbo. Track directions seemed to be more affected by winds in climbing compared with level flights, which may be explained by birds not starting to partially compensate for wind drift until they have reached cruising altitudes. PMID:26085501

  13. Ensheathing cell-conditioned medium directs the differentiation of human umbilical cord blood cells into aldynoglial phenotype cells.

    PubMed

    Ponce-Regalado, María Dolores; Ortuño-Sahagún, Daniel; Zarate, Carlos Beas; Gudiño-Cabrera, Graciela

    2012-06-01

    Despite their similarities to bone marrow precursor cells (PC), human umbilical cord blood (HUCB) PCs are more immature and, thus, they exhibit greater plasticity. This plasticity is evident by their ability to proliferate and spontaneously differentiate into almost any cell type, depending on their environment. Moreover, HUCB-PCs yield an accessible cell population that can be grown in culture and differentiated into glial, neuronal and other cell phenotypes. HUCB-PCs offer many potential therapeutic benefits, particularly in the area of neural replacement. We sought to induce the differentiation of HUCB-PCs into glial cells, known as aldynoglia. These cells can promote neuronal regeneration after lesion and they can be transplanted into areas affected by several pathologies, which represents an important therapeutic strategy to treat central nervous system damage. To induce differentiation to the aldynoglia phenotype, HUCB-PCs were exposed to different culture media. Mononuclear cells from HUCB were isolated and purified by identification of CD34 and CD133 antigens, and after 12 days in culture, differentiation of CD34+ HUCB-PCs to an aldynoglia phenotypic, but not that of CD133+ cells, was induced in ensheathing cell (EC)-conditioned medium. Thus, we demonstrate that the differentiation of HUCB-PCs into aldynoglia cells in EC-conditioned medium can provide a new source of aldynoglial cells for use in transplants to treat injuries or neurodegenerative diseases.

  14. Evidence for a Proapoptotic Role of Matrix Metalloproteinase-26 in Human Prostate Cancer Cells and Tissues

    PubMed Central

    Khamis, Zahraa I.; Iczkowski, Kenneth A.; Man, Yan-Gao; Bou-Dargham, Mayassa J.; Sang, Qing-Xiang Amy

    2016-01-01

    Matrix metalloproteinases (MMPs) play intricate roles in cancer progression; some promote invasion and angiogenesis while others suppress tumor growth. For example, human MMP-26/endometase/matrilysin-2 was reported to be either protective or pro-tumorigenic. Our previous reports suggested pro-invasion and anti-inflammation properties in prostate cancer. Here, we provide evidence for a protective role of MMP-26 in the prostate. MMP-26 expression levels in androgen-repressed human prostate cancer (ARCaP) cells, transfected with sense or anti-sense MMP-26 cDNA, are directly correlated with those of the pro-apoptotic marker Bax. Immunohistochemical staining of prostate cancer tissue samples shows similar protein expression patterns, correlating the expression levels of MMP-26 and Bax in benign, neoplastic, and invasive prostate cancer tissues. The MMP-26 protein levels were upregulated in high grade prostate intraepithelial neoplasia (HGPIN) and decreased during the course of disease progression. Further analysis using an indirect terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that many tumor cells expressing MMP-26 were undergoing apoptosis. This study showed that the high level of MMP-26 expression is positively correlated with the presence of apoptotic cells. This pro-apoptotic role of MMP-26 in human prostate cancer cells and tissues may enhance our understanding of the paradoxical roles of MMP-26 in tumor invasion and progression. PMID:26722363

  15. Stat3 Activation in Urothelial Stem Cells Leads to Direct Progression to Invasive Bladder Cancer

    PubMed Central

    Ho, Philip Levy; Lay, Erica Julianne; Jian, Weiguo; Parra, Diana; Chan, Keith Syson

    2012-01-01

    Two subtypes of human bladder cancer, noninvasive papillary and muscle-invasive cancer, develop through independent pathologic and molecular pathways. Human invasive bladder cancer frequently develops without prior clinical evidence of a noninvasive tumor stage. However, an animal model that recapitulates this unique clinical progression of invasive bladder cancer has not yet been developed. In this study, we created a novel transgenic mouse model of invasive bladder cancer by targeting an active dimerized form of Stat3 to the basal cells of bladder epithelium. When exposed to the carcinogen nitrosamine, Stat3-transgenic mice developed invasive cancer directly from carcinoma in situ (CIS), bypassing the noninvasive papillary tumor stage. Remarkably, invasive bladder cancer driven by active Stat3 was predominantly composed of stem cells, which were characterized by cytokeratin 14 (CK14) staining and enhanced tumor sphere-forming ability. Active Stat3 was also shown to localize to the nucleus of human invasive bladder cancers that were primarily composed of CK14+ stem cells. Together, our findings show that Stat3-induced stem cell expansion plays a critical role in the unique clinical progression of invasive bladder cancer through the CIS pathway. PMID:22532166

  16. A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex

    NASA Astrophysics Data System (ADS)

    Cruz-Martín, Alberto; El-Danaf, Rana N.; Osakada, Fumitaka; Sriram, Balaji; Dhande, Onkar S.; Nguyen, Phong L.; Callaway, Edward M.; Ghosh, Anirvan; Huberman, Andrew D.

    2014-03-01

    How specific features in the environment are represented within the brain is an important unanswered question in neuroscience. A subset of retinal neurons, called direction-selective ganglion cells (DSGCs), are specialized for detecting motion along specific axes of the visual field. Despite extensive study of the retinal circuitry that endows DSGCs with their unique tuning properties, their downstream circuitry in the brain and thus their contribution to visual processing has remained unclear. In mice, several different types of DSGCs connect to the dorsal lateral geniculate nucleus (dLGN), the visual thalamic structure that harbours cortical relay neurons. Whether direction-selective information computed at the level of the retina is routed to cortical circuits and integrated with other visual channels, however, is unknown. Here we show that there is a di-synaptic circuit linking DSGCs with the superficial layers of the primary visual cortex (V1) by using viral trans-synaptic circuit mapping and functional imaging of visually driven calcium signals in thalamocortical axons. This circuit pools information from several types of DSGCs, converges in a specialized subdivision of the dLGN, and delivers direction-tuned and orientation-tuned signals to superficial V1. Notably, this circuit is anatomically segregated from the retino-geniculo-cortical pathway carrying non-direction-tuned visual information to deeper layers of V1, such as layer 4. Thus, the mouse harbours several functionally specialized, parallel retino-geniculo-cortical pathways, one of which originates with retinal DSGCs and delivers direction- and orientation-tuned information specifically to the superficial layers of the primary visual cortex. These data provide evidence that direction and orientation selectivity of some V1 neurons may be influenced by the activation of DSGCs.

  17. A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex.

    PubMed

    Cruz-Martín, Alberto; El-Danaf, Rana N; Osakada, Fumitaka; Sriram, Balaji; Dhande, Onkar S; Nguyen, Phong L; Callaway, Edward M; Ghosh, Anirvan; Huberman, Andrew D

    2014-03-20

    How specific features in the environment are represented within the brain is an important unanswered question in neuroscience. A subset of retinal neurons, called direction-selective ganglion cells (DSGCs), are specialized for detecting motion along specific axes of the visual field. Despite extensive study of the retinal circuitry that endows DSGCs with their unique tuning properties, their downstream circuitry in the brain and thus their contribution to visual processing has remained unclear. In mice, several different types of DSGCs connect to the dorsal lateral geniculate nucleus (dLGN), the visual thalamic structure that harbours cortical relay neurons. Whether direction-selective information computed at the level of the retina is routed to cortical circuits and integrated with other visual channels, however, is unknown. Here we show that there is a di-synaptic circuit linking DSGCs with the superficial layers of the primary visual cortex (V1) by using viral trans-synaptic circuit mapping and functional imaging of visually driven calcium signals in thalamocortical axons. This circuit pools information from several types of DSGCs, converges in a specialized subdivision of the dLGN, and delivers direction-tuned and orientation-tuned signals to superficial V1. Notably, this circuit is anatomically segregated from the retino-geniculo-cortical pathway carrying non-direction-tuned visual information to deeper layers of V1, such as layer 4. Thus, the mouse harbours several functionally specialized, parallel retino-geniculo-cortical pathways, one of which originates with retinal DSGCs and delivers direction- and orientation-tuned information specifically to the superficial layers of the primary visual cortex. These data provide evidence that direction and orientation selectivity of some V1 neurons may be influenced by the activation of DSGCs.

  18. Management of Child and Adolescent Eating Disorders: The Current Evidence Base and Future Directions

    ERIC Educational Resources Information Center

    Gowers, Simon; Bryant-Waugh, Rachel

    2004-01-01

    Although eating disorders in children and adolescents remain a serious cause of morbidity and mortality, the evidence base for effective interventions is surprisingly weak. The adult literature is growing steadily, but this is mainly with regard to psychological therapies for bulimia nervosa and to some extent in the field of pharmacotherapy. This…

  19. Burnout and Risk of Cardiovascular Disease: Evidence, Possible Causal Paths, and Promising Research Directions

    ERIC Educational Resources Information Center

    Melamed, Samuel; Shirom, Arie; Toker, Sharon; Berliner, Shlomo; Shapira, Itzhak

    2006-01-01

    Burnout is characterized by emotional exhaustion, physical fatigue, and cognitive weariness, resulting from prolonged exposure to work-related stress. The authors review the accumulated evidence suggesting that burnout and the related concept of vital exhaustion are associated with increased risk of cardiovascular disease and…

  20. Direct targeting of cancer cells: a multiparameter approach.

    PubMed

    Heinrich, Eileen L; Welty, Lily Anne Y; Banner, Lisa R; Oppenheimer, Steven B

    2005-01-01

    Lectins have been widely used in cell surface studies and in the development of potential anticancer drugs. Many past studies that have examined lectin toxicity have only evaluated the effects on cancer cells, not their non-cancer counterparts. In addition, few past studies have evaluated the relationship between lectin-cell binding and lectin toxicity on both cell types. Here we examine these parameters in one study: lectin-cell binding and lectin toxicity with both cancer cells and their normal counterparts. We found that the human colon cancer cell line CCL-220/Colo320DM bound to agarose beads derivatized with Phaseolus vulgaris agglutinin (PHA-L) and wheat germ agglutinin (WGA), while the non-cancer human colon cell line CRL-1459/CCD-18Co did not. When these lectins were tested for their effects on cell viability in culture, both cell lines were affected by the lectins but at 6, 48 and 72 h incubation times, PHA-L was most toxic to the cancer cell line in a concentration dependent manner. At 48 h incubation, WGA was more toxic to the cancer cell line. The results suggest that it may be possible to develop lectin protocols that selectively target cancer cells for death. In any case, examination of both malignant cells and their non-malignant counterparts, analysis of their binding characteristics to immobilized lectins, and examination of the toxicity of free lectins in culture, provides a multiparameter model for obtaining more comprehensive information than from more limited approaches.

  1. Methods for continuous direct carbon fuel cell operation with a circulating electrolyte slurry

    DOEpatents

    Harjes, Daniel I.; Dineen, Jr., D. Andrew; Guo, Liang; Calo, Joseph M.; Bloomfield, Valerie J.

    2017-02-07

    The present invention relates to methods and systems related to fuel cells, and in particular, to direct carbon fuel cells. The methods and systems relate to cleaning and removal of components utilized and produced during operation of the fuel cell, regeneration of components utilized during operation of the fuel cell, and generating power using the fuel cell.

  2. Pluripotent Stem Cells: Current Understanding and Future Directions

    PubMed Central

    Romito, Antonio

    2016-01-01

    Pluripotent stem cells have the ability to undergo self-renewal and to give rise to all cells of the tissues of the body. However, this definition has been recently complicated by the existence of distinct cellular states that display these features. Here, we provide a detailed overview of the family of pluripotent cell lines derived from early mouse and human embryos and compare them with induced pluripotent stem cells. Shared and distinct features of these cells are reported as additional hallmark of pluripotency, offering a comprehensive scenario of pluripotent stem cells. PMID:26798367

  3. Directing cell migration and organization via nanocrater-patterned cell-repellent interfaces

    PubMed Central

    Jeon, Hojeong; Koo, Sangmo; Reese, Willie Mae; Loskill, Peter; Grigoropoulos, Costas P.; Healy, Kevin E.

    2015-01-01

    Although adhesive interactions between cells and nanostructured interfaces have been studied extensively1–6, there is a paucity of data on how nanostructured interfaces repel cells by directing cell migration and cell-colony organization. Here, by using multiphoton ablation lithography7 to pattern surfaces with nanoscale craters of various aspect ratios and pitches, we show that the surfaces altered the cells’ focal-adhesion size and distribution, thus affecting cell morphology, migration and ultimately localization. We also show that nanocrater pitch can disrupt the formation of mature focal adhesions to favour the migration of cells toward higher-pitched regions, which present increased planar area for the formation of stable focal adhesions. Moreover, by designing surfaces with variable pitch but constant nanocrater dimensions, we were able to create circular and striped cellular patterns. Our surface-patterning approach, which does not involve chemical treatments and can be applied to various materials, represents a simple method to control cell behaviour on surfaces. PMID:26213899

  4. Fast-crawling cell types migrate to avoid the direction of periodic substratum stretching.

    PubMed

    Okimura, Chika; Ueda, Kazuki; Sakumura, Yuichi; Iwadate, Yoshiaki

    2016-07-03

    To investigate the relationship between mechanical stimuli from substrata and related cell functions, one of the most useful techniques is the application of mechanical stimuli via periodic stretching of elastic substrata. In response to this stimulus, Dictyostelium discoideum cells migrate in a direction perpendicular to the stretching direction. The origins of directional migration, higher migration velocity in the direction perpendicular to the stretching direction or the higher probability of a switch of migration direction to perpendicular to the stretching direction, however, remain unknown. In this study, we applied periodic stretching stimuli to neutrophil-like differentiated HL-60 cells, which migrate perpendicular to the direction of stretch. Detailed analysis of the trajectories of HL-60 cells and Dictyostelium cells obtained in a previous study revealed that the higher probability of a switch of migration direction to that perpendicular to the direction of stretching was the main cause of such directional migration. This directional migration appears to be a strategy adopted by fast-crawling cells in which they do not migrate faster in the direction they want to go, but migrate to avoid a direction they do not want to go.

  5. Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice

    PubMed Central

    Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E.; Qiang, Sheng

    2015-01-01

    Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China. PMID:26012494

  6. Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice.

    PubMed

    Zhang, Jingxu; Lu, Zuomei; Dai, Weimin; Song, Xiaoling; Peng, Yufa; Valverde, Bernal E; Qiang, Sheng

    2015-05-27

    Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China.

  7. Quantifying the weight of fingerprint evidence through the spatial relationship, directions and types of minutiae observed on fingermarks.

    PubMed

    Neumann, Cedric; Champod, Christophe; Yoo, Mina; Genessay, Thibault; Langenburg, Glenn

    2015-03-01

    This paper presents a statistical model for the quantification of the weight of fingerprint evidence. Contrarily to previous models (generative and score-based models), our model proposes to estimate the probability distributions of spatial relationships, directions and types of minutiae observed on fingerprints for any given fingermark. Our model is relying on an AFIS algorithm provided by 3M Cogent and on a dataset of more than 4,000,000 fingerprints to represent a sample from a relevant population of potential sources. The performance of our model was tested using several hundreds of minutiae configurations observed on a set of 565 fingermarks. In particular, the effects of various sub-populations of fingers (i.e., finger number, finger general pattern) on the expected evidential value of our test configurations were investigated. The performance of our model indicates that the spatial relationship between minutiae carries more evidential weight than their type or direction. Our results also indicate that the AFIS component of our model directly enables us to assign weight to fingerprint evidence without the need for the additional layer of complex statistical modeling involved by the estimation of the probability distributions of fingerprint features. In fact, it seems that the AFIS component is more sensitive to the sub-population effects than the other components of the model. Overall, the data generated during this research project contributes to support the idea that fingerprint evidence is a valuable forensic tool for the identification of individuals.

  8. Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

    PubMed Central

    Ichihara, Yoshinori; Doi, Toru; Ryu, Youngjae; Nagao, Motoshi; Sawada, Yasuhiro

    2016-01-01

    Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4‐dideoxy‐1,4‐imino‐d‐arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC‐rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU‐positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate‐mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α‐cyano‐4‐hydroxy‐cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986–995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27861886

  9. Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.

    PubMed

    Ichihara, Yoshinori; Doi, Toru; Ryu, Youngjae; Nagao, Motoshi; Sawada, Yasuhiro; Ogata, Toru

    2017-05-01

    Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC-rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU-positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate-mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α-cyano-4-hydroxy-cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986-995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  10. Parent ADHD and Evidence-Based Treatment for Their Children: Review and Directions for Future Research.

    PubMed

    Chronis-Tuscano, Andrea; Wang, Christine H; Woods, Kelsey E; Strickland, Jennifer; Stein, Mark A

    2017-04-01

    One fourth to one half of parents of children with attention-deficit/hyperactivity disorder (ADHD) have ADHD themselves, complicating delivery of evidence-based child behavioral and pharmacological treatments. In this article, we review the literature examining the relation between parent ADHD and outcomes following behavioral and pharmacological treatments for children with ADHD. We also review research that has incorporated treatment of parent ADHD (either alone or in combination with child treatment) with the goal of improving parenting and child outcomes. Finally, we offer recommendations for future research on the relation between parent ADHD and evidence-based treatment outcomes for their children, with the purpose of advancing the science and informing clinical care of these families.

  11. Engineering nanoscale stem cell niche: direct stem cell behavior at cell-matrix interface.

    PubMed

    Zhang, Yan; Gordon, Andrew; Qian, Weiyi; Chen, Weiqiang

    2015-09-16

    Biophysical cues on the extracellular matrix (ECM) have proven to be significant regulators of stem cell behavior and evolution. Understanding the interplay of these cells and their extracellular microenvironment is critical to future tissue engineering and regenerative medicine, both of which require a means of controlled differentiation. Research suggests that nanotopography, which mimics the local, nanoscale, topographic cues within the stem cell niche, could be a way to achieve large-scale proliferation and control of stem cells in vitro. This Progress Report reviews the history and contemporary advancements of this technology, and pays special attention to nanotopographic fabrication methods and the effect of different nanoscale patterns on stem cell response. Finally, it outlines potential intracellular mechanisms behind this response.

  12. A DNA damage checkpoint in Caulobacter crescentus inhibits cell division through a direct interaction with FtsW.

    PubMed

    Modell, Joshua W; Hopkins, Alexander C; Laub, Michael T

    2011-06-15

    Following DNA damage, cells typically delay cell cycle progression and inhibit cell division until their chromosomes have been repaired. The bacterial checkpoint systems responsible for these DNA damage responses are incompletely understood. Here, we show that Caulobacter crescentus responds to DNA damage by coordinately inducing an SOS regulon and inhibiting the master regulator CtrA. Included in the SOS regulon is sidA (SOS-induced inhibitor of cell division A), a membrane protein of only 29 amino acids that helps to delay cell division following DNA damage, but is dispensable in undamaged cells. SidA is sufficient, when overproduced, to block cell division. However, unlike many other regulators of bacterial cell division, SidA does not directly disrupt the assembly or stability of the cytokinetic ring protein FtsZ, nor does it affect the recruitment of other components of the cell division machinery. Instead, we provide evidence that SidA inhibits division by binding directly to FtsW to prevent the final constriction of the cytokinetic ring.

  13. Direct measurement of cell detachment force on single cells using a new electromechanical method.

    PubMed

    Francis, G W; Fisher, L R; Gamble, R A; Gingell, D

    1987-05-01

    We describe a new device in which an accurately measured force is applied to individual adherent cells while the topography of the adhesion zone is simultaneously monitored. The force is applied via a flexible glass micropipette, attached by suction to the cell under study, and is calculated directly from the measured pipette deflection. Regions of close contact in the adhesion zone are observed using interference reflection microscopy. We have used the device to measure the force required to detach human red blood cells from hydrophobic and hydrophilic glass surfaces, and to detach Dictyostelium discoideum amoebae from a hydrophobic glass surface. The measured forces per unit length of contact perimeter are within an order of magnitude of the tensions required for membrane rupture.

  14. Direct evidence for the spin cycloid in strained nanoscale bismuth ferrite thin films

    PubMed Central

    Bertinshaw, Joel; Maran, Ronald; Callori, Sara J.; Ramesh, Vidya; Cheung, Jeffery; Danilkin, Sergey A.; Lee, Wai Tung; Hu, Songbai; Seidel, Jan; Valanoor, Nagarajan; Ulrich, Clemens

    2016-01-01

    Magnonic devices that utilize electric control of spin waves mediated by complex spin textures are an emerging direction in spintronics research. Room-temperature multiferroic materials, such as bismuth ferrite (BiFeO3), would be ideal candidates for this purpose. To realize magnonic devices, a robust long-range spin cycloid with well-known direction is desired, since it is a prerequisite for the magnetoelectric coupling. Despite extensive investigation, the stabilization of a large-scale uniform spin cycloid in nanoscale (100 nm) thin BiFeO3 films has not been accomplished. Here, we demonstrate cycloidal spin order in 100 nm BiFeO3 thin films through the careful choice of crystallographic orientation, and control of the electrostatic and strain boundary conditions. Neutron diffraction, in conjunction with X-ray diffraction, reveals an incommensurate spin cycloid with a unique [11] propagation direction. While this direction is different from bulk BiFeO3, the cycloid length and Néel temperature remain equivalent to bulk at room temperature. PMID:27585637

  15. Phonetic Category Cues in Adult-Directed Speech: Evidence from Three Languages with Distinct Vowel Characteristics

    ERIC Educational Resources Information Center

    Pons, Ferran; Biesanz, Jeremy C.; Kajikawa, Sachiyo; Fais, Laurel; Narayan, Chandan R.; Amano, Shigeaki; Werker, Janet F.

    2012-01-01

    Using an artificial language learning manipulation, Maye, Werker, and Gerken (2002) demonstrated that infants' speech sound categories change as a function of the distributional properties of the input. In a recent study, Werker et al. (2007) showed that Infant-directed Speech (IDS) input contains reliable acoustic cues that support distributional…

  16. Measuring Racial Discrimination in the Housing Market: Direct and Indirect Evidence.

    ERIC Educational Resources Information Center

    Clark, William A. V.

    1993-01-01

    Reevaluates statistical studies by G. Galster (1986, 1987, 1988) and Galster and W. Keeney (1988) of segregation in housing, reanalyzing one of four model equations. The effects of discrimination are smaller than postulated previously. Direct estimates from housing discrimination surveys provide a rationale for these smaller effects. (SLD)

  17. Anxiety and Reading Difficulties in Early Elementary School: Evidence for Unidirectional- or Bi-Directional Relations?

    ERIC Educational Resources Information Center

    Grills-Taquechel, Amie E.; Fletcher, Jack M.; Vaughn, Sharon R.; Stuebing, Karla K.

    2012-01-01

    The present study examined competing models of the bi-directional influences of anxiety and reading achievement. Participants were 153 ethnically-diverse children (84 male, 69 female) from general education classes evaluated in the winter and spring of their first-grade academic year. Children completed standardized measures of reading achievement…

  18. Intentional Forgetting Reduces Color-Naming Interference: Evidence from Item-Method Directed Forgetting

    ERIC Educational Resources Information Center

    Lee, Yuh-shiow; Lee, Huang-mou; Fawcett, Jonathan M.

    2013-01-01

    In an item-method-directed forgetting task, Chinese words were presented individually, each followed by an instruction to remember or forget. Colored probe items were presented following each memory instruction requiring a speeded color-naming response. Half of the probe items were novel and unrelated to the preceding study item, whereas the…

  19. Evidence for the involvement of a K+ channel in isosmotic cell shrinking in vestibular dark cells.

    PubMed

    Wangemann, P; Shiga, N; Welch, C; Marcus, D C

    1992-09-01

    Cell volume changes were measured in dark cells. Isosmotic addition of 21.4 mM K+, Rb+, Cs+, or NH4+ to a control solution containing 3.6 mM K+ caused piretanide-sensitive cell swelling (initial rate for K+, 0.100 +/- 0.005 microns/s; n = 119), suggesting dependence on the Na(+)-Cl(-)-K+ cotransporter. Subsequent isosmotic removal of 21.4 mM K+ caused piretanide-insensitive cell shrinking (initial rate, -0.104 +/- 0.005 microns/s; n = 119), which was inhibited by barium, lidocaine, quinidine, quinine, verapamil, and 4-aminopyridine but not tetraethylammonium (TEA) or glibenclamide, suggesting the involvement of K+ channel(s). Barium, lidocaine, quinine, quinidine, and 4-aminopyridine caused cell swelling in control solution (initial rate for barium, 0.011 +/- 0.004 microns/s; n = 6), suggesting that the K+ channel is also involved in efflux under control conditions. Cell shrinking was slowed by 21.4 mM extracellular K+, Rb+, or Cs+ but unaffected by Na+, Li+, TEA+, or NH4+ (all in the presence of piretanide and compared with N-methyl-D-glucamine), supporting the notion that the efflux mechanism is permeable to and/or inhibited by K+, Rb+, and Cs+. Cell shrinking was slowed by the presumed replacement of intracellular K+ by Cs+ but not by Rb+. Circumstantial evidence suggests that this putative K+ channel is present in the basolateral membrane. The physiological relevance of such a K+ channel might encompass regulatory volume decrease during K+ secretion.

  20. Micropatterning different cell types with microarray amplification of natural directional persistence.

    PubMed

    Mun, Kyu-Shik; Kumar, Girish; Co, Carlos C; Ho, Chia-Chi

    2013-02-01

    In vivo, different cell types assemble in specific patterns to form functional tissues. Reproducing this process in vitro by designing scaffold materials to direct cells precisely to the right locations at the right time is important for the next generation of biomaterials. Here, using microarray amplification of natural directional persistence (MANDIP), simultaneous assembly of fibroblasts and endothelial cells is demonstrated by directing their long-range migration. Amplification of the directional persistence occurs through morphology-induced polarity and the asymmetric positioning of individual microsized adhesive islands that restrict lamellipodia attachment, and thus migration, to one preset direction. Quantitative analysis of cell migration on different MANDIP designs yields insight to the relative importance of the asymmetric island shapes and their arrangement. The approach enables spatial patterning of different cell types with micrometer-scale precision over large areas for investigation of cell-cell interactions within complex tissue architectures.

  1. Natural killer cell biology: an update and future directions.

    PubMed

    Campbell, Kerry S; Hasegawa, Jun

    2013-09-01

    Natural killer (NK) cells constitute a minor subset of normal lymphocytes that initiate innate immune responses toward tumor and virus-infected cells. They can mediate spontaneous cytotoxicity toward these abnormal cells and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses. Significant progress has been made in the past 2 decades to improve our understanding of NK cell biology. Here we review recent discoveries, including a better comprehension of the "education" of NK cells to achieve functional competence during their maturation and the discovery of "memory" responses by NK cells, suggesting that they might also contribute to adaptive immunity. The improved understanding of NK cell biology has forged greater awareness that these cells play integral early roles in immune responses. In addition, several promising clinical therapies have been used to exploit NK cell functions in treating patients with cancer. As our molecular understanding improves, these and future immunotherapies should continue to provide promising strategies to exploit the unique functions of NK cells to treat cancer, infections, and other pathologic conditions.

  2. Experimental models of acute renal failure and erythropoietin: what evidence of a direct effect?

    PubMed

    Sturiale, Alessio; Campo, Susanna; Crascì, Eleonora; Aloisi, Carmela; Buemi, Michele

    2007-01-01

    The kidney can achieve a structural and functional recovery after the damage induced by ischemia and reperfusion. This is due to the regeneration of epithelial tubular cells, the intervention of immature cells mainly localized in the medulla, and a small number of bone marrow-derived stem cells. In many instances, however, recovery is delayed or does not occur at all. The mechanisms allowing the renal cells to de-differentiate still need to be clarified in order to find a therapeutic approach that can amplify this ability and then stop the fibroid involution and the progression toward renal failure. Several authors have hypothesized a protective effect of EPO against ischemic and cytotoxic renal damage and observed that patients precociously treated with EPO showed a slower progression of renal failure. EPO has been demonstrated to have proliferative and anti-apoptotic effects in ischemia-reperfusion models in the brain and cell cultures. Moreover, EPO can mobilize stem cells and increase the plasmatic levels and the renal expression of VEGF. These effects seem to be dose-dependent and could be due to the activation of signal transduction systems, like Jak and STAT. In the presence of high doses of exogenous EPO or during the treatment with long-acting EPO-like molecules, non-specific receptors may be activated through a low-affinity link. Further investigations are needed to determine new therapeutic applications for EPO and other analogous hormones. Very long-acting molecules or molecules with cyto-protective but no erythropoietic effect may represent useful tools in the study of the molecular mechanisms underlying EPO's action and may have a rapid and safe therapeutic application.

  3. Evidence of a Hopf bifurcation in frog hair cells.

    PubMed Central

    Ospeck, M; Eguíluz, V M; Magnasco, M O

    2001-01-01

    The membrane potential of hair cells in the low-frequency hearing organ of the bullfrog, the amphibian papilla, sinusoidally oscillates at small amplitude in the absence of acoustical input. We stimulate the cell with a series of periodic currents close to this natural frequency and observe that its current-to-voltage transfer function is compressively nonlinear, having a large gain for small stimuli and a smaller gain for larger currents. Along with the spontaneous oscillation, this implies that the cell is poised close to a dynamical instability such as a Hopf bifurcation, because distant from the instability the transfer function becomes linear. The cell's frequency selectivity is enhanced for small stimuli. Simulations show that the cell's membrane capacitance is effectively reduced due to a current gain provided by this dynamical instability. We propose that the Hopf resonance is widely used by transducer cells on the sensory periphery to achieve small-signal amplification. PMID:11371437

  4. Phenomenological and evidence based research in ego state therapy: recognized and unrecognized successes and future directions.

    PubMed

    Hageman, Joan H; Frederick, Claire

    2013-07-01

    The status of research in ego state therapy is examined against the backdrop of 20th and 21st century developments in the philosophy of science and the emerging recognition of the subjective as a vital element in all science. Attention is paid to the phenomenological method because until recently phenomenological studies have been the basis for the standards of care and training in ego state therapy as well as in many aspects of hypnotically facilitated psychotherapy. The importance of bringing an end to the "science wars" through the integration of the subjective and the objective, of phenomenological studies and evidence-based studies in ego state therapy and hypnosis research, is proposed.

  5. Direct evidence of Lowenstein's rule violation in swelling high-charge micas.

    PubMed

    Pavón, E; Osuna, F J; Alba, M D; Delevoye, L

    2014-07-07

    The structure of high-charged micas, Na-n-micas (n = 2 and 4), a family of synthetic silicates with a wide range of applications, was investigated through the use of (17)O solid-state NMR at natural abundance in order to preserve quantitative spectral information. The use of a very high-field and highly sensitive probehead, together with (17)O NMR literature data allowed for the detection of an isolated signal at 26 ppm, assigned partially to AlOAl, as evidence of the violation of Lowenstein's rule for Na-4-mica.

  6. Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration.

    PubMed

    Ray, Arja; Lee, Oscar; Win, Zaw; Edwards, Rachel M; Alford, Patrick W; Kim, Deok-Ho; Provenzano, Paolo P

    2017-04-12

    Directed migration by contact guidance is a poorly understood yet vital phenomenon, particularly for carcinoma cell invasion on aligned collagen fibres. We demonstrate that for single cells, aligned architectures providing contact guidance cues induce constrained focal adhesion maturation and associated F-actin alignment, consequently orchestrating anisotropic traction stresses that drive cell orientation and directional migration. Consistent with this understanding, relaxing spatial constraints to adhesion maturation either through reduction in substrate alignment density or reduction in adhesion size diminishes the contact guidance response. While such interactions allow single mesenchymal-like cells to spontaneously 'sense' and follow topographic alignment, intercellular interactions within epithelial clusters temper anisotropic cell-substratum forces, resulting in substantially lower directional response. Overall, these results point to the control of contact guidance by a balance of cell-substratum and cell-cell interactions, modulated by cell phenotype-specific cytoskeletal arrangements. Thus, our findings elucidate how phenotypically diverse cells perceive ECM alignment at the molecular level.

  7. Design and Operation of an Electrochemical Methanol Concentration Sensor for Direct Methanol Fuel Cell Systems

    NASA Technical Reports Server (NTRS)

    Narayanan, S. R.; Valdez, T. I.; Chun, W.

    2000-01-01

    The development of a 150-Watt packaged power source based on liquid feed direct methanol fuel cells is being pursued currently at the Jet propulsion Laboratory for defense applications. In our studies we find that the concentration of methanol in the fuel circulation loop affects the electrical performance and efficiency the direct methanol fuel cell systems significantly. The practical operation of direct methanol fuel cell systems, therefore, requires accurate monitoring and control of methanol concentration. The present paper reports on the principle and demonstration of an in-house developed electrochemical sensor suitable for direct methanol fuel cell systems.

  8. Calpain-Mediated positional information directs cell wall orientation to sustain plant stem cell activity, growth and development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eukaryotic development and stem cell control depend on the integration of cell positional sensing with cell cycle control and cell wall positioning, yet few factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1) gene encoding the unique plant calpain protein is fundamental f...

  9. Direct-to-consumer stem cell marketing and regulatory responses.

    PubMed

    Sipp, Douglas

    2013-09-01

    There is a large, poorly regulated international market of putative stem cell products, including transplants of processed autologous stem cells from various tissues, cell processing devices, cosmetics, and nutritional supplements. Despite the absence of rigorous scientific research in the form of randomized clinical trials to support the routine use of such products, the market appears to be growing and diversifying. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries, including the United States, have begun to step up their enforcement activities to protect patients and the integrity of health care markets.

  10. The Role of Massage in Sports Performance and Rehabilitation: Current Evidence and Future Direction

    PubMed Central

    2008-01-01

    Background Massage is a popular treatment choice of athletes, coaches, and sports physical therapists. Despite its purported benefits and frequent use, evidence demonstrating its efficacy is scarce. Purpose To identify current literature relating to sports massage and its role in effecting an athlete's psychological readiness, in enhancing sports performance, in recovery from exercise and competition, and in the treatment of sports related musculoskeletal injuries. Methods Electronic databases were used to identify papers relevant to this review. The following keywords were searched: massage, sports injuries, athletic injuries, physical therapy, rehabilitation, delayed onset muscle soreness, sports psychology, sports performance, sports massage, sports recovery, soft tissue mobilization, deep transverse friction massage, pre-event, and post exercise. Results Research studies pertaining to the following general categories were identified and reviewed: pre-event (physiological and psychological variables), sports performance, recovery, and rehabilitation. Discussion Despite the fact clinical research has been performed, a poor appreciation exists for the appropriate clinical use of sports massage. Conclusion Additional studies examining the physiological and psychological effects of sports massage are necessary in order to assist the sports physical therapist in developing and implementing clinically significant evidence based programs or treatments. PMID:21509135

  11. Epigenetics of Posttraumatic Stress Disorder: Current Evidence, Challenges, and Future Directions.

    PubMed

    Zannas, Anthony S; Provençal, Nadine; Binder, Elisabeth B

    2015-09-01

    Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder that is thought to emerge from complex interactions among traumatic events and multiple genetic factors. Epigenetic regulation lies at the heart of these interactions and mediates the lasting effects of the environment on gene regulation. An increasing body of evidence in human subjects with PTSD supports a role for epigenetic regulation of distinct genes and pathways in the pathogenesis of PTSD. The role of epigenetic regulation is further supported by studies examining fear conditioning in rodent models. Although this line of research offers an exciting outlook for future epigenetic research in PTSD, important limitations include the tissue specificity of epigenetic modifications, the phenomenologic definition of the disorder, and the challenge of translating molecular evidence across species. These limitations call for studies that combine data from postmortem human brain tissue and animal models, assess longitudinal epigenetic changes in living subjects, and examine dimensional phenotypes in addition to diagnoses. Moreover, examining the environmental, genetic, and epigenetic factors that promote resilience to trauma may lead to important advances in the field.

  12. Palladium(II)-catalyzed direct alkoxylation of arenes: evidence for solvent-assisted concerted metalation deprotonation.

    PubMed

    Anand, Megha; Sunoj, Raghavan B

    2011-09-16

    Density functional theory investigations on the mechanism of palladium acetate catalyzed direct alkoxylation of N-methoxybenzamide in methanol reveal that the key steps involve solvent-assisted N-H as well as C-H bond activations. The transition state for the critical palladium-carbon bond formation through a concerted metalation deprotonation (CMD) process leading to a palladacycle intermediate has been found to be more stable in the methanol-assisted pathway as compared to an unassisted route.

  13. Increased cytosolic calcium stimulates exocytosis in bovine lactotrophs. Direct evidence from changes in membrane capacitance

    PubMed Central

    1991-01-01

    The patch-clamp technique has been used to measure changes in membrane capacitance (Cm) of bovine lactotrophs in order to monitor fluctuations in cell surface area associated with exo- and endocytosis. Cells were prepared by an enrichment procedure and cultured for up to 14 d before use. Under whole-cell recording, cell cytoplasm was dialyzed with various Ca2(+)-containing solutions. The resting Cm of 6.05 +/- 1.68 pF was found to correlate well with squared cell radius, suggesting a specific Cm of 0.8 microF/cm2. Discrete Cm steps of 2-10 fF were recorded, which most likely reflect single fusion and retrieval events of prolactin-containing granules (0.2-0.6 microns in diameter). High Ca2+ resulted in a Cm increase of 20-50% from the resting value, demonstrating a role for [Ca2+]i in stimulus-secretion coupling. Spontaneous Cm changes have also been recorded, which presumably reflect prolactin secretion supported by a tonic influx of Ca2+ through the membrane. This is supported by the following findings: addition of Co2+ diminished or reversed the spontaneous Cm changes and decreased resting [Ca2+]i; and membrane depolarization increased Cm, indicating the role of voltage-activated channels in stimulus-secretion coupling. As bovine lactotrophs have been found to be largely devoid of spontaneous electrical activity, a mechanism involving modulation of a tonic Ca2+ influx is proposed; this is shown to provide adequate control of basal and triggered secretion monitored by Cm. PMID:2037838

  14. Two stages of directed forgetting: Electrophysiological evidence from a short-term memory task.

    PubMed

    Gao, Heming; Cao, Bihua; Qi, Mingming; Wang, Jing; Zhang, Qi; Li, Fuhong

    2016-06-01

    In this study, a short-term memory test was used to investigate the temporal course and neural mechanism of directed forgetting under different memory loads. Within each trial, two memory items with high or low load were presented sequentially, followed by a cue indicating whether the presented items should be remembered. After an interval, subjects were asked to respond to the probe stimuli. The ERPs locked to the cues showed that (a) the effect of cue type was initially observed during the P2 (160-240 ms) time window, with more positive ERPs for remembering relative to forgetting cues; (b) load effects were observed during the N2-P3 (250-500 ms) time window, with more positive ERPs for the high-load than low-load condition; (c) the cue effect was also observed during the N2-P3 time window, with more negative ERPs for forgetting versus remembering cues. These results demonstrated that directed forgetting involves two stages: task-relevance identification and information discarding. The cue effects during the N2 epoch supported the view that directed forgetting is an active process.

  15. Evidence for a Direct Effect of the NAD+ Precursor Acipimox on Muscle Mitochondrial Function in Humans

    PubMed Central

    van de Weijer, Tineke; Phielix, Esther; Bilet, Lena; Williams, Evan G.; Ropelle, Eduardo R.; Bierwagen, Alessandra; Livingstone, Roshan; Nowotny, Peter; Sparks, Lauren M.; Paglialunga, Sabina; Szendroedi, Julia; Havekes, Bas; Moullan, Norman; Pirinen, Eija; Hwang, Jong-Hee; Schrauwen-Hinderling, Vera B.; Hesselink, Matthijs K.C.; Auwerx, Johan

    2015-01-01

    Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD+) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD+ precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m2) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD+ levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD+ boosters can also directly affect skeletal muscle mitochondrial function in humans. PMID:25352640

  16. Extracellular vesicles from infected cells: potential for direct pathogenesis

    PubMed Central

    Schwab, Angela; Meyering, Shabana S.; Lepene, Ben; Iordanskiy, Sergey; van Hoek, Monique L.; Hakami, Ramin M.; Kashanchi, Fatah

    2015-01-01

    Infections that result in natural or manmade spread of lethal biological agents are a concern and require national and focused preparedness. In this manuscript, as part of an early diagnostics and pathogen treatment strategy, we have focused on extracellular vesicles (EVs) that arise following infections. Although the field of biodefense does not currently have a rich resource in EVs literature, none the less, similar pathogens belonging to the more classical emerging and non-emerging diseases have been studied in their EV/exosomal contents and function. These exosomes are formed in late endosomes and released from the cell membrane in almost every cell type in vivo. These vesicles contain proteins, RNA, and lipids from the cells they originate from and function in development, signal transduction, cell survival, and transfer of infectious material. The current review focuses on how different forms of infection exploit the exosomal pathway and how exosomes can be exploited artificially to treat infection and disease and potentially also be used as a source of vaccine. Virally-infected cells can secrete viral as well as cellular proteins and RNA in exosomes, allowing viruses to cause latent infection and spread of miRNA to nearby cells prior to a subsequent infection. In addition to virally-infected host cells, bacteria, protozoa, and fungi can all release small vesicles that contain pathogen-associated molecular patterns, regulating the neighboring uninfected cells. Examples of exosomes from both virally and bacterially infected cells point toward a re-programming network of pathways in the recipient cells. Finally, many of these exosomes contain cytokines and miRNAs that in turn can effect gene expression in the recipient cells through the classical toll-like receptor and NFκB pathway. Therefore, although exosomes do not replicate as an independent entity, they however facilitate movement of infectious material through tissues and may be the cause of many

  17. Nanosecond pulsed electric fields (nsPEF) induce direct electric field effects and biological effects on human colon carcinoma cells.

    PubMed

    Hall, Emily H; Schoenbach, Karl H; Beebe, Stephen J

    2005-05-01

    Nanosecond pulsed electric fields (nsPEFs) are ultrashort pulses with high electric field intensity (kV/cm) and high power (megawatts), but low energy density (mJ/cc). To determine roles for p53 in response to nsPEFs, HCT116 cells (p53+/+ and p53-/-) were exposed to nsPEF and analyzed for membrane integrity, phosphatidylserine externalization, caspase activation, and cell survival. Decreasing plasma membrane effects were observed in both HCT116p53+/+ and p53-/- cells with decreasing pulse durations and/or decreasing electric fields. However, addition of ethidium homodimer-1 and Annexin-V-FITC post-pulse demonstrated greater fluorescence in p53-/- versus p53+/+ cells, suggesting a postpulse p53-dependent biological effect at the plasma membrane. Caspase activity was significantly higher than nonpulsed cells only in the p53-/- cells. HCT116 cells exhibited greater survival in response to nsPEFs than HL-60 and Jurkat cells, but survival was more evident for HCT116p53+/+ cells than for HCT116p53-/- cells. These results indicate that nsPEF effects on HCT116 cells include (1) apparent direct electric field effects, (2) biological effects that are p53-dependent and p53-independent, (3) actions on mechanisms that originate at the plasma membranes and at intracellular structures, and (4) an apparent p53 protective effect. NsPEF applications provide a means to explore intracellular structures and functions that can reveal mechanisms in health and disease.

  18. Direct binding of a myasthenia gravis related epitope to MHC class II molecules on living murine antigen-presenting cells.

    PubMed Central

    Mozes, E; Dayan, M; Zisman, E; Brocke, S; Licht, A; Pecht, I

    1989-01-01

    MHC gene products present antigenic epitopes to the antigen receptor on T cells. Nevertheless, direct binding of such epitopes to MHC class II proteins on normal living antigen-presenting cells (APCs) has not yet been demonstrated. We have previously shown a significant difference in the ability of T cells of myasthenia gravis (MG) patients to proliferate in response to the synthetic peptide p195-212 of the human acetylcholine receptor (AChR) alpha-subunit in comparison to healthy controls. The observed proliferative responses correlated significantly with HLA-DR5. Moreover, lymph node cells of various mouse strains that were primed with the T cell epitope, p195-212, were found to proliferate to different extents. To investigate these observations further, we designed an assay for direct binding of p195-212 to MHC class II proteins on the surface of freshly prepared splenic adherent cells. Binding of a biotinylated p195-212 was monitored using phycoerythrin-avidin by flow cytometry. Fifteen to sixty per cent of the cells were labeled following incubation with the biotinylated peptide. Binding was observed only to splenic adherent cells derived from mouse strains of which T cells were capable of proliferating in response to p195-212. The binding specificity, in terms of epitope structure and its site of interaction on the cells, was shown by its inhibition with an excess of the unlabeled peptide or with the relevant monoclonal anti-I-A antibodies. These results constitute the first direct evidence for the specific binding of a T cell epitope to live APC. PMID:2480232

  19. Glioma-associated endothelial cells show evidence of replicative senescence

    SciTech Connect

    Charalambous, Christiana; Virrey, Jenilyn; Kardosh, Adel; Jabbour, Mark N.; Qazi-Abdullah, Lubna; Pen, Ligaya; Zidovetzki, Raphael; Schoenthal, Axel H.; Chen, Thomas C.; Hofman, Florence M. . E-mail: hofman@usc.edu

    2007-04-01

    The innately programmed process of replicative senescence has been studied extensively with respect to cancer, but primarily from the perspective of tumor cells overcoming this stringent innate barrier and acquiring the capacity for unlimited proliferation. In this study, we focus on the potential role of replicative senescence affecting the non-transformed endothelial cells of the blood vessels within the tumor microenvironment. Based on the well-documented aberrant structural and functional features of blood vessels within solid tumors, we hypothesized that tumor-derived factors may lead to premature replicative senescence in tumor-associated brain endothelial cells (TuBEC). We show here that glioma tissue, but not normal brain tissue, contains cells that express the signature of replicative senescence, senescence-associated {beta}-galactosidase (SA-{beta}-gal), on CD31-positive endothelial cells. Primary cultures of human TuBEC stain for SA-{beta}-gal and exhibit characteristics of replicative senescence, including increased levels of the cell cycle inhibitors p21 and p27, increased resistance to cytotoxic drugs, increased growth factor production, and inability to proliferate. These data provide the first demonstration that tumor-derived brain endothelial cells may have reached an end-stage of differentiation known as replicative senescence and underscore the need for anti-angiogenic therapies to target this unique tumor-associated endothelial cell population.

  20. Raman scattering evidence of hydrohalite formation on frozen yeast cells.

    PubMed

    Okotrub, K A; Surovtsev, N V

    2013-02-01

    We studied yeast cells in physiological solution during freezing by Raman microspectroscopy technique. The purpose was to find out the origin of a sharp peak near ∼3430cm(-1) in Raman spectrum of frozen mammalian cells, observed earlier (J. Dong et al., Biophys. J. 99 (2010) 2453), which presumably could be used as an indicator of intracellar ice appearance. We have shown that this line (actually doublet of 3408 and 3425cm(-1)) corresponds to Raman spectrum of hydrohalite (NaCl⋅2H(2)O), which is formed as the result of the eutectic crystallization of the liquid solution around the cells. We also show that the spatial distribution of hydrohalite in the sample significantly depends on the cooling rate. At lower cooling rate (1°C/min), products of eutectic crystallization form layer on the cell surface which thickness varies for different cells and can reach ∼1μm in thickness. At higher cooling rate (20°C/min), the hydrohalite distribution appears more homogeneous, in the sample, and the eutectic crystallization layer around the cells was estimated to be less than ∼20nm. These experimental results are consistent with scenarios predicted by the two-factor hypothesis for freezing induced cell injury. This work demonstrates a potential of Raman microspectroscopy to study peculiarities of the eutectic crystallization around single cells in vivo with the high spatial resolution.

  1. Investigation of In Vitro Bone Cell Adhesion and Proliferation on Ti Using Direct Current Stimulation.

    PubMed

    Bodhak, Subhadip; Bose, Susmita; Kinsel, William C; Bandyopadhyay, Amit

    2012-12-01

    Our objective was to establish an in vitro cell culture protocol to improve bone cell attachment and proliferation on Ti substrate using direct current stimulation. For this purpose, a custom made electrical stimulator was developed and a varying range of direct currents, from 5 to 25 µA, were used to study the current stimulation effect on bone cells cultured on conducting Ti samples in vitro. Cell-materials interaction was studied for a maximum of 5 days by culturing with human fetal osteoblast cells (hFOB). The direct current was applied in every 8 h time interval and the duration of electrical stimulation was kept constant at 15 min for all cases. In vitro results showed that direct current stimulation significantly favored bone cell attachment and proliferation in comparison to nonstimulated Ti surface. Immunochemistry and confocal microscopy results confirmed that the cell adhesion was most pronounced on 25 µA direct current stimulated Ti surfaces as hFOB cells expressed higher vinculin protein with increasing amount of direct current. Furthermore, MTT assay results established that cells grew 30% higher in number under 25 µA electrical stimulation as compared to nonstimulated Ti surface after 5 days of culture period. In this work we have successfully established a simple and cost effective in vitro protocol offering easy and rapid analysis of bone cell-materials interaction which can be used in promotion of bone cell attachment and growth on Ti substrate using direct current electrical stimulation in an in vitro model.

  2. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier.

    PubMed

    Sonoda, N; Furuse, M; Sasaki, H; Yonemura, S; Katahira, J; Horiguchi, Y; Tsukita, S

    1999-10-04

    Claudins, comprising a multigene family, constitute tight junction (TJ) strands. Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half. We examined the effects of the COOH-terminal half fragment of CPE (C-CPE) on TJs in L transfectants expressing claudin-1 to -4 (C1L to C4L, respectively), and in MDCK I cells expressing claudin-1 and -4. C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2. In the presence of C-CPE, reconstituted TJ strands in C3L cells gradually disintegrated and disappeared from their cell surface. In MDCK I cells incubated with C-CPE, claudin-4 was selectively removed from TJs with its concomitant degradation. At 4 h after incubation with C-CPE, TJ strands were disintegrated, and the number of TJ strands and the complexity of their network were markedly decreased. In good agreement with the time course of these morphological changes, the TJ barrier (TER and paracellular flux) of MDCK I cells was downregulated by C-CPE in a dose-dependent manner. These findings provided evidence for the direct involvement of claudins in the barrier functions of TJs.

  3. Direct metabolomics for plant cells by live single-cell mass spectrometry.

    PubMed

    Fujii, Takashi; Matsuda, Shuichi; Tejedor, Mónica Lorenzo; Esaki, Tsuyoshi; Sakane, Iwao; Mizuno, Hajime; Tsuyama, Naohiro; Masujima, Tsutomu

    2015-09-01

    Live single-cell mass spectrometry (live MS) provides a mass spectrum that shows thousands of metabolite peaks from a single live plant cell within minutes. By using an optical microscope, a cell is chosen for analysis and a metal-coated nanospray microcapillary tip is used to remove the cell's contents. After adding a microliter of ionization solvent to the opposite end of the tip, the trapped contents are directly fed into the mass spectrometer by applying a high voltage between the tip and the inlet port of the spectrometer to induce nanospray ionization. Proteins are not detected because of insufficient sensitivity. Metabolite peaks are identified by exact mass or tandem mass spectrometry (MS/MS) analysis, and isomers can be separated by combining live MS with ion-mobility separation. By using this approach, spectra can be acquired in 10 min. In combination with metabolic maps and/or molecular databases, the data can be annotated into metabolic pathways; the data analysis takes 30 min to 4 h, depending on the MS/MS data availability from databases. This method enables the analysis of a number of metabolites from a single cell with rapid sampling at sub-attomolar-level sensitivity.

  4. Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation

    PubMed Central

    McCabe, Kathryn L.; Kunzevitzky, Noelia J.; Chiswell, Brian P.; Xia, Xin; Goldberg, Jeffrey L.; Lanza, Robert

    2015-01-01

    Aim To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs) for transplantation in patients with corneal endothelial dystrophies. Materials and Methods Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression. Results hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1) and Na+/K+ATPaseα1 (ATPA1) on the apical surface in monolayer culture, and produced the key proteins of Descemet’s membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2). Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis. Conclusion hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium. PMID:26689688

  5. Evidence of innate lymphoid cell redundancy in humans

    PubMed Central

    Vély, Frédéric; Barlogis, Vincent; Vallentin, Blandine; Neven, Bénédicte; Piperoglou, Christelle; Perchet, Thibaut; Petit, Maxime; Yessaad, Nadia; Touzot, Fabien; Bruneau, Julie; Mahlaoui, Nizar; Zucchini, Nicolas; Farnarier, Catherine; Michel, Gérard; Moshous, Despina; Blanche, Stéphane; Dujardin, Arnaud; Spits, Hergen; Distler, Jörg H. W.; Ramming, Andreas; Picard, Capucine; Golub, Rachel; Fischer, Alain; Vivier, Eric

    2016-01-01

    Innate lymphoid cells (ILCs) have potent immune functions in experimental conditions in mice, but their contribution to immunity in natural conditions in humans remains unclear. We investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in SCID patients carrying mutations of IL2RG or JAK3. T cell reconstitution was observed in SCID patients upon hematopoietic stem cell transplantation (HSCT), but the patients still exhibited drastic reduction of ILCs in the absence of myeloablation, at the exception of rare cases of ILC1 reconstitution. Remarkably, the observed ILC deficiencies were not associated with any particular susceptibility to disease, with a follow-up extending from 7 to 39 years after HSCT. We thus report here the first cases of selective ILC deficiency in humans, and show that ILCs may be dispensable in natural conditions, if T cells are present and B cell function is preserved. PMID:27618553

  6. Direct Reacting Anolyte-Catholyte Fuel Cell for Hybrid Energy Sources

    DTIC Science & Technology

    2005-07-11

    401-832-5293. 20050719 026 Attorney Docket No. 82872 Customer No. 23523 DIRECT REACTING ANOLYTE -CATHOLYTE FUEL CELL FOR HYBRID ENERGY SOURCES TO ALL...PAUL A. NASSER, Esq. Reg. No. 53372 1 Attorney Docket No. 82872 2 3 DIRECT REACTING ANOLYTE -CATHOLYTE FUEL CELL 4 FOR HYBRID ENERGY SOURCES 5 6...14 The present invention relates generally to a fuel cell, and 15 more particularly to a fuel cell wherein both the anolyte and 16 the catholyte are

  7. Evidence for rostro-caudal functional organization in multiple brain areas related to goal-directed behavior.

    PubMed

    Dixon, Matthew L; Fox, Kieran C R; Christoff, Kalina

    2014-07-14

    The functional organization of brain areas supporting goal-directed behavior is debated. Some accounts suggest a rostro-caudal organization, while others suggest a broad recruitment as part of a multiple demand network. We used fMRI and an anatomical region of interest (ROI) approach to test which account better characterizes the organization of key brain areas related to goal-directed behavior: the lateral prefrontal cortex (LPFC), medial prefrontal cortex (MPFC), cingulate cortex, and insula. Subjects performed a cognitive control task with distinct trial events corresponding to rule representation, rule maintenance, action execution, and monitoring progress towards an overarching motivational goal. The use of ROIs allowed us to look for evidence of rostro-caudal gradients during each event separately. Our results provide strong evidence for rostro-caudal gradients in all regions. During the action execution period, activation was robust in caudal ROIs and decreased linearly moving to rostral ROIs in the LPFC, cingulate cortex, and MPFC. Conversely, during the goal monitoring period, activation was weak in caudal ROIs and increased linearly moving to the rostral ROIs in the aforementioned regions. The insula exhibited the reverse pattern. These findings provide evidence for rostro-caudal organization in multiple regions within the same study. More importantly, they demonstrate that rostro-caudal gradients can be observed during individual trial events, ruling out confounding factors such as task difficulty.

  8. Direct Exposure to Ethanol Disrupts Junctional Cell-Cell Contact and Hippo-YAP Signaling in HL-1 Murine Atrial Cardiomyocytes

    PubMed Central

    Noritake, Kanako; Aki, Toshihiko; Funakoshi, Takeshi; Unuma, Kana; Uemura, Koichi

    2015-01-01

    Direct exposure of cardiomyocytes to ethanol causes cardiac damage such as cardiac arrythmias and apoptotic cell death. Cardiomyocytes are connected to each other through intercalated disks (ID), which are composed of a gap junction (GJ), adherens junction, and desmosome. Changes in the content as well as the subcellular localization of connexin43 (Cx43), the main component of the cardiac GJ, are reportedly involved in cardiac arrythmias and subsequent damage. Recently, the hippo-YAP signaling pathway, which links cellular physical status to cell proliferation, differentiation, and apoptosis, has been implicated in cardiac homeostasis under physiological as well as pathological conditions. This study was conducted to explore the possible involvement of junctional intercellular communication, mechanotransduction through cytoskeletal organization, and the hippo-YAP pathway in cardiac damage caused by direct exposure to ethanol. HL-1 murine atrial cardiac cells were used since these cells retain cardiac phenotypes through ID formation and subsequent synchronous contraction. Cells were exposed to 0.5–2% ethanol; significant apoptotic cell death was observed after exposure to 2% ethanol for 48 hours. A decrease in Cx43 levels was already observed after 3 hours exposure to 2% ethanol, suggesting a rapid degradation of this protein. Upon exposure to ethanol, Cx43 translocated into lysosomes. Cellular cytoskeletal organization was also dysregulated by ethanol, as demonstrated by the disruption of myofibrils and intermediate filaments. Coinciding with the loss of cell-cell adherence, decreased phosphorylation of YAP, a hippo pathway effector, was also observed in ethanol-treated cells. Taken together, the results provide evidence that cells exposed directly to ethanol show 1) impaired cell-cell adherence/communication, 2) decreased cellular mechanotransduction by the cytoskeleton, and 3) a suppressed hippo-YAP pathway. Suppression of hippo-YAP pathway signaling should be

  9. The Use of Evidence in Public Debates in the Media: The Case of Swiss Direct-Democratic Campaigns in the Health Policy Sector

    ERIC Educational Resources Information Center

    Stucki, Iris

    2016-01-01

    This article analyses the reporting of evidence in Swiss direct-democratic campaigns in the health policy sector, assuming that an informed public helps democracy function successfully. A content analysis of the media's news reporting shows that of 5030 media items retrieved, a reference to evidence is found in 6.8%. The voter receives evidence in…

  10. Hormono-biological therapy in metastatic breast cancer: preclinical evidence, clinical studies and future directions.

    PubMed

    Tonini, Giuseppe; Schiavon, Gaia; Fratto, Maria Elisabetta; Vincenzi, Bruno; Santini, Daniele

    2008-02-01

    Breast cancer growth is regulated by coordinated actions of the estrogen receptor (ER) and various growth factor receptor signalling pathways. This complex interactive signalling potentially explains some of the reasons behind endocrine therapy action and resistance. Recent research into the molecular biology of ER signalling has revealed new molecular targets which, if present in cancer cells, might be additionally targeted using various signal transduction inhibitors to overcome or prevent resistance to endocrine therapy. The dynamic inverse relationship between the expression of ER and growth factor receptors brings more excitement to the potential of restoring ER expression in apparently ER-negative cells by inhibition of growth factor signalling. The multiple pathways involved in activating ERs also provide a rationale for combining endocrine and non-endocrine therapies that block different signalling pathways. Ongoing clinical trials promise to further improve the present care for breast cancer patients.

  11. CD8+ T-cell interaction with HCV replicon cells: evidence for both cytokine- and cell-mediated antiviral activity.

    PubMed

    Liu, Chen; Zhu, Haizhen; Tu, Zhengkun; Xu, Yi-Ling; Nelson, David R

    2003-06-01

    The interaction between the host immune response and infected hepatocytes plays a central role in the pathogenesis of hepatitis C virus (HCV). The lack of a suitable animal or in vitro model has hindered our understanding of the host T-cell/HCV interaction. Our aim was to develop an in vitro model to study the mechanisms of HCV-specific T-cell-mediated antiviral and cytolytic function. The HCV replicon was HLA typed and lymphocytes were obtained from an HLA class I-matched subject. CD8(+) T cells were expanded with 2 HCV-specific/HLA-restricted peptides for NS3. Lymphocyte preparations were cocultured with HCV replicon (FCA1) and control (Huh7) cells labeled with (51)Cr. After a 48-hour incubation, the cells were harvested for RNA extraction. Standard blocking assays were performed in the presence of anti-interferon gamma (IFN-gamma), anti-tumor necrosis factor alpha (TNF-alpha), and anti-FasL. Cytolytic activity was measured by (51)Cr release. HCV replicon cells express homozygous HLA-A11 alleles and present HCV nonstructural proteins. HCV-specific expansion of CD8(+) cells led to a 10-fold decrease in HCV replication by Northern blot analysis and 21% specific lysis of FCA1 cells (compared with 2% of control Huh7 cells). Twenty percent of this antiviral activity was independent of T-cell binding, suggesting cytokine-mediated antiviral activity. The CD8(+) antiviral effect was markedly reduced by blocking either IFN-gamma or FasL but was unaffected by blocking TNF-alpha. In conclusion, HCV-specific CD8(+) cells inhibit viral RNA replication by cytokine-mediated and direct cytolytic effects. This T-cell/HCV subgenomic replicon system represents a model for the investigation of CD8 cell interaction with HCV-infected hepatocytes.

  12. Have we found conclusive evidence for dark matter through direct detection experiments?

    NASA Astrophysics Data System (ADS)

    Yang, Jun

    2014-04-01

    A WIMP-model-independent method is used to examine the existing evidence for low mass dark matter. Using XENON100's recent result of 224.6 live days × 34 kg exposure and PICASSO's result that was published in 2012, we have obtained constraints on the couplings |an| < 0.4 and |ap| < 0.3, corresponding to spin-dependent cross-sections of σn<2.5×10-38 cm and σp<1.4×10-38 cm2 for a WIMP mass of 10 GeV/c2. It is shown that the spin-independent isospin-violating dark matter model also fails to reconcile the recent result from XENON100 with the positive results from DAMA, CoGeNT and CDMS-II.

  13. First evidence of direct CP violation in charmless two-body decays of Bs0 mesons.

    PubMed

    Aaij, R; Abellan Beteta, C; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amhis, Y; Anderson, J; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Arrabito, L; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Bachmann, S; Back, J J; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bates, A; Bauer, C; Bauer, Th; Bay, A; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Benayoun, M; Bencivenni, G; Benson, S; Benton, J; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blanks, C; Blouw, J; Blusk, S; Bobrov, A; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Büchler-Germann, A; Burducea, I; Bursche, A; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cattaneo, M; Cauet, Ch; Charles, M; Charpentier, Ph; Chiapolini, N; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Corti, G; Couturier, B; Cowan, G A; Currie, R; D'Ambrosio, C; David, P; David, P N Y; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Lorenzi, F; De Miranda, J M; De Paula, L; De Simone, P; Decamp, D; Deckenhoff, M; Degaudenzi, H; Del Buono, L; Deplano, C; Derkach, D; Deschamps, O; Dettori, F; Dickens, J; Dijkstra, H; Diniz Batista, P; Domingo Bonal, F; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Dzhelyadin, R; Dziurda, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisele, F; Eisenhardt, S; Ekelhof, R; Eklund, L; Elsasser, Ch; Elsby, D; Esperante Pereira, D; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Fernandez Albor, V; Ferro-Luzzi, M; Filippov, S; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosi