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Sample records for cells direct evidence

  1. Multiple origins of spontaneously arising micronuclei in HeLa cells: Direct evidence from long-term live cell imaging

    Rao Xiaotang; Zhang Yingyin; Yi Qiyi; Hou Heli; Xu Bo; Chu Liang; Huang Yun; Zhang Wenrui; Fenech, Michael; Shi Qinghua

    2008-01-01

    Although micronuclei (MNi) are extensively used to evaluate genotoxic effects and chromosome instability, the most basic issue regarding their origins has not been completely addressed due to limitations of traditional methods. Recently, long-term live cell imaging was developed to monitor the dynamics of single cell in a real-time and high-throughput manner. In the present study, this state-of-the-art technique was employed to examine spontaneous micronucleus (MN) formation in untreated HeLa cells. We demonstrate that spontaneous MNi are derived from incorrectly aligned chromosomes in metaphase (displaced chromosomes, DCs), lagging chromosomes (LCs) and broken chromosome bridges (CBs) in later mitotic stages, but not nuclear buds in S phase. However, most of bipolar mitoses with DCs (91.29%), LCs (73.11%) and broken CBs (88.93%) did not give rise to MNi. Our data also show directly, for the first time, that MNi could originate spontaneously from (1) MNi already presented in the mother cells; (2) nuclear fragments that appeared during mitosis with CB; and (3) chromosomes being extruded into a minicell which fused with one of the daughter cells later. Quantitatively, most of MNi originated from LCs (63.66%), DCs (10.97%) and broken CBs (9.25%). Taken together, these direct evidences show that there are multiple origins for spontaneously arising MNi in HeLa cells and each mechanism contributes to overall MN formation to different extents

  2. Multiple origins of spontaneously arising micronuclei in HeLa cells: Direct evidence from long-term live cell imaging

    Rao Xiaotang; Zhang Yingyin; Yi Qiyi; Hou Heli; Xu Bo; Chu Liang; Huang Yun; Zhang Wenrui [Laboratory of Molecular and Cell Genetics, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China); Fenech, Michael [CSIRO Human Nutrition, PO Box 10041, Adelaide BC, Adelaide, SA 5000 (Australia); Shi Qinghua [Laboratory of Molecular and Cell Genetics, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China)], E-mail: qshi@ustc.edu.cn

    2008-11-10

    Although micronuclei (MNi) are extensively used to evaluate genotoxic effects and chromosome instability, the most basic issue regarding their origins has not been completely addressed due to limitations of traditional methods. Recently, long-term live cell imaging was developed to monitor the dynamics of single cell in a real-time and high-throughput manner. In the present study, this state-of-the-art technique was employed to examine spontaneous micronucleus (MN) formation in untreated HeLa cells. We demonstrate that spontaneous MNi are derived from incorrectly aligned chromosomes in metaphase (displaced chromosomes, DCs), lagging chromosomes (LCs) and broken chromosome bridges (CBs) in later mitotic stages, but not nuclear buds in S phase. However, most of bipolar mitoses with DCs (91.29%), LCs (73.11%) and broken CBs (88.93%) did not give rise to MNi. Our data also show directly, for the first time, that MNi could originate spontaneously from (1) MNi already presented in the mother cells; (2) nuclear fragments that appeared during mitosis with CB; and (3) chromosomes being extruded into a minicell which fused with one of the daughter cells later. Quantitatively, most of MNi originated from LCs (63.66%), DCs (10.97%) and broken CBs (9.25%). Taken together, these direct evidences show that there are multiple origins for spontaneously arising MNi in HeLa cells and each mechanism contributes to overall MN formation to different extents.

  3. Lack of direct evidence for a functional role of voltage-operated calcium channels in juxtaglomerular cells

    Kurtz, A; Skott, O; Chegini, S

    1990-01-01

    in patch-clamped nor in intact Furaester-loaded cells. Moreover, basal renin secretion from a preparation enriched in mouse juxtaglomerular cells and from rat glomeruli with attached juxtaglomerular cells was not inhibited when extracellular potassium was isoosmotically increased to 56 mmol/l. In mouse...... kidney slices, however, depolarizing potassium concentrations caused a delayed inhibition at 56 mmol/l and a delayed stimulation of renin secretion at 110 mmol/l. Taken together, our study does not provide direct evidence for a role of voltage-activated calcium channels in the regulation of calcium...

  4. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Berman, Abigail T.; James, Sara St.; Rengan, Ramesh

    2015-01-01

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning

  5. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Abigail T. Berman

    2015-07-01

    Full Text Available Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT, through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC, as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

  6. Direct hydrocarbon fuel cells

    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.

  7. Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood

    Herndon, Thomas M; Chen, Shih-Ann; Saba, Nakhle S

    2017-01-01

    of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide ((2)H) in vivo labeling...... method in which patients consumed deuterated (heavy) water ((2)H2O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth...

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

    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.

    2006-01-01

    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

  9. Direct evidence that FK506 inhibition of FcepsilonRI-mediated exocytosis from RBL mast cells involves calcineurin.

    Hultsch, T; Brand, P; Lohmann, S; Saloga, J; Kincaid, R L; Knop, J

    1998-05-01

    FcepsilonRI-mediated exocytosis of preformed mediators from mast cells and basophils (e.g. histamine, serotonin, beta-hexosaminidase) is sensitive to the immunosuppressants cyclosporin A and FK506 (IC50 200 and 4 nM, respectively) but not rapamycin. The mechanism of inhibition does not appear to involve tyrosine phosphorylation, hydrolysis of inositol phosphates or calcium flux. Here we report experiments using a molecular approach to assess the role of calcineurin, a serine/threonine phosphatase thought to be the primary pharmacological target of these drugs. Calcineurin's activity requires association of its catalytic (A) subunit with an intrinsic regulatory (B) subunit. We hypothesized that calcineurin-sensitive signalling events should be affected by the depletion of calcineurin B subunits, thereby reducing the number of active A:B complexes. We therefore transfected rat basophilic leukemia (RBL) cells with an inhibitory (dominant negative) form of the calcineurin A subunit, which binds the calcineurin B subunit with high affinity but does not possess catalytic activity (B subunit knock-out, BKO). In these transfected cells, the dose-response curve for the inhibition of FcepsilonRI-mediated exocytosis by FK506 was shifted to the left, indicating an increased drug sensitivity of BKO-transfected cells. We conclude that FK506 inhibition of FcepsilonRI-mediated exocytosis in mast cells specifically targets calcineurin activity.

  10. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab

    Beyer, G.J.; Soloviev, D.; Buchegger, F.; Miederer, M.; Vranjes-Duric, S.; Comor, J.J.; Kuenzi, G.; Hartley, O.; Senekowitsch-Schmidtke, R.

    2004-01-01

    This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10 6 Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 μg unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%±4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%±2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with 149 Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

  11. Direct Methanol Fuel Cell, DMFC

    Amornpitoksuk, P.

    2003-09-01

    Full Text Available Direct Methanol Fuel Cell, DMFC is a kind of fuel cell using methanol as a fuel for electric producing. Methanol is low cost chemical substance and it is less harmful than that of hydrogen fuel. From these reasons it can be commercial product. The electrocatalytic reaction of methanol fuel uses Pt-Ru metals as the most efficient catalyst. In addition, the property of membrane and system designation are also effect to the fuel cell efficient. Because of low power of methanol fuel cell therefore, direct methanol fuel cell is proper to use for the energy source of small electrical devices and vehicles etc.

  12. Direct Evidence on Learning by Exporting

    Grimpe, Christoph; Belderbos, Rene

    2014-01-01

    learning and export learning – an issue that has been ignored in prior studies. Learning from foreign customers is more prevalent than learning from foreign competitors. Firms’ underlying innovation strategy appears as an important moderator of the propensity to learn and of the relationship between......We examine first direct evidence on the occurrence of learning by exporting, using unique survey data for German innovating firms on the role of (foreign) customers and competitors as sources of ideas and impetus for innovation. Export intensive firms frequently benefit simultaneously from domestic...... learning and innovativeness. Firms adopting a strategy of technology leadership more often exhibit effective learning from diverse foreign customers and this learning is strongly associated with innovative sales – but mostly so if combined with domestic customer learning. In contrast, firms that have...

  13. GLP-1 regulation of glucagon, somatostatin and insulin in naidm patients: evidence of direct inhibition of A - cells by GLP - 1

    Naveed, A.K.; Khan, F.A.

    2006-01-01

    Glucagon-like peptide-1 (7-36) amide (GLP-1) is released from the gut into the circulation after meals and is the most potent physiological insulinotropic hormone in man. In contrast to presently available therapeutic agents for non-insulin dependent diabetes mellitus (NIDDM), GLP-1 has the advantages of both suppressing glucagon secretion and delaying gastric emptying. We report first study of subcutaneous GLP-1 treatment to determine the optimum dose required to control the NIDDM. Seven patients, with poorly controlled NIDDM were entered in the study who visited at four visits with intervals of 2-4 days and received saline, 40, 100 and 200 nmol subcutaneous GLP-1, immediately after meals. A standerdized test meal was given. A significant hypoglycaemic response (p<0.05) was achieved in patients given 40, 100 and 200 nmol GLP-1. An increase in insulin levels (p<0.05) was observed as compared to control, when 100 and 200 nmol GLP-1 was given. There was no significant difference between insulin and glucose responses when 100 and 200 nmol of GLP-1 were compared with each. The glucagon levels were significant less (p< 0.05) in patients, given 100 and 200 nmol doses as compared to control. Glucagon inhibitory response to GLP-1, when given in doses of 200 nmol was more (p< 0.05) than 100 nmol GLP-1. Somatostatin levels decreased dose dependently by GLP-1 infusions. It is concluded that suppression of glucagon secretion and inhibition of somatostatin corresponded to dose of GLP-1 used. There was no significant difference in glucose and insulin levels between 100 and 200 nmol GLP-1 doses. Therefore, present study has helped in ascertaining the optimum dose for GLP-1 i.e. 100 nmol. Down regulation of GLP-1 receptors on cells occurred at higher dose while, A and D cells inhibition occurred dose dependently. These results revealed that GLP-1 affects A and D cells directly and also through stimulation of cells. These findings will significantly contribute in the possible role

  14. Direct evidence for a chronic CD8+-T-cell-mediated immune reaction to tax within the muscle of a human T-cell leukemia/lymphoma virus type 1-infected patient with sporadic inclusion body myositis.

    Ozden, Simona; Cochet, Madeleine; Mikol, Jacqueline; Teixeira, Antonio; Gessain, Antoine; Pique, Claudine

    2004-10-01

    Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4(+) T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8(+) T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4(+) T cells and CD8(+) T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.

  15. CAUDAL MEDULLARY PATHWAYS TO LUMBOSACRAL MOTONEURONAL CELL GROUPS IN THE CAT - EVIDENCE FOR DIRECT PROJECTIONS POSSIBLY REPRESENTING THE FINAL COMMON PATHWAY FOR LORDOSIS

    VANDERHORST, VGJM; HOLSTEGE, G

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  16. Caudal Medullary Pathways To Lumbosacral Motoneuronal Cell Groups In The Cat; Evidence For Direct Projections Possibly Representing The Final Common Pathway For Lordosis.

    VanderHorst, Veronique G.J.M.; Holstege, Gert

    1995-01-01

    The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase

  17. CHANGES OF BUOYANT DENSITY DURING THE S-PHASE OF THE CELL-CYCLE - DIRECT EVIDENCE DEMONSTRATED IN ACUTE MYELOID-LEUKEMIA BY FLOW-CYTOMETRIC

    DAENEN, S; HUIGES, W; MODDERMAN, E; HALIE, MR

    Studies with synchronized or exponentially growing bacteria and mammalian cell lines are not able to demonstrate small changes in buoyant density during the cell cycle. Flowcytometric analysis of density separated acute myeloid leukemia cells, a system not dependent on time-related variables, shows

  18. Oriented collagen fibers direct tumor cell intravasation

    Han, Weijing; Chen, Shaohua; Yuan, Wei; Fan, Qihui; Tian, Jianxiang; Wang, Xiaochen; Chen, Longqing; Zhang, Xixiang; Wei, Weili; Liu, Ruchuan; Qu, Junle; Jiao, Yang; Austin, Robert H.; Liu, Liyu

    2016-01-01

    that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

  19. Evidence of directional and stabilizing selection in contemporary humans.

    Sanjak, Jaleal S; Sidorenko, Julia; Robinson, Matthew R; Thornton, Kevin R; Visscher, Peter M

    2018-01-02

    Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.

  20. Methods of conditioning direct methanol fuel cells

    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.

  1. Oriented collagen fibers direct tumor cell intravasation

    Han, Weijing

    2016-09-24

    In this work, we constructed a Collagen I-Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell-ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

  2. Lightweight Stacks of Direct Methanol Fuel Cells

    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.

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

    Warinner, C.; Hendy, J.; Speller, C.

    2014-01-01

    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...

  4. Advances in direct oxidation methanol fuel cells

    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.

  5. Directed forgetting of visual symbols: evidence for nonverbal selective rehearsal.

    Hourihan, Kathleen L; Ozubko, Jason D; MacLeod, Colin M

    2009-12-01

    Is selective rehearsal possible for nonverbal information? Two experiments addressed this question using the item method directed forgetting paradigm, where the advantage of remember items over forget items is ascribed to selective rehearsal favoring the remember items. In both experiments, difficult-to-name abstract symbols were presented for study, followed by a recognition test. Directed forgetting effects were evident for these symbols, regardless of whether they were or were not spontaneously named. Critically, a directed forgetting effect was observed for unnamed symbols even when the symbols were studied under verbal suppression to prevent verbal rehearsal. This pattern indicates that a form of nonverbal rehearsal can be used strategically (i.e., selectively) to enhance memory, even when verbal rehearsal is not possible.

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

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Improved Direct Methanol Fuel Cell Stack

    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.

  8. Stem cell clinics online: the direct-to-consumer portrayal of stem cell medicine.

    Lau, Darren; Ogbogu, Ubaka; Taylor, Benjamin; Stafinski, Tania; Menon, Devidas; Caulfield, Timothy

    2008-12-04

    Despite the immature state of stem cell medicine, patients are seeking and accessing putative stem cell therapies in an "early market" in which direct-to-consumer advertising via the internet likely plays an important role. We analyzed stem cell clinic websites and appraised the relevant published clinical evidence of stem cell therapies to address three questions about the direct-to-consumer portrayal of stem cell medicine in this early market: What sorts of therapies are being offered? How are they portrayed? Is there clinical evidence to support the use of these therapies? We found that the portrayal of stem cell medicine on provider websites is optimistic and unsubstantiated by peer-reviewed literature.

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

    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.

  10. Prevention of lethal graft-versus-host disease in mice by monoclonal antibodies directed against T cells or their subsets.I.Evidence for the induction of a state of tolerance based on suppression

    Knulst, A.C.; Tibbe, G.J.M.; Noort, W.A.; Bril-Bazuin, C.; Benner, R.; Savelkoul, H.F.J.

    1994-01-01

    Lethal GVHD in the fully allogeneic BALB/c (donor)-(C57BL x CBA)F1 (recipient) mouse strain combination could be prevented by a single dose of IgG2b monoclonal antibodies (moAb) directed to T cells. The influence of the time of administration of this moAb after GVHD induction and the effect of

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

    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

  12. Direct fuel cell product design improvement

    Maru, H.C.; Farooque, M. [Energy Research Corp., Danbury, CT (United States)

    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.

  13. GLYCAN-DIRECTED CAR-T CELLS.

    Steentoft, Catharina; Migliorini, Denis; King, Tiffany R; Mandel, Ulla; June, Carl H; Posey, Avery D

    2018-01-23

    Cancer immunotherapy is rapidly advancing in the treatment of a variety of hematopoietic cancers, including pediatric acute lymphoblastic leukemia and diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs are genetically encoded artificial T cell receptors that combine the antigen specificity of an antibody with the machinery of T cell activation. However, implementation of CAR technology in the treatment of solid tumors has been progressing much slower. Solid tumors are characterized by a number of challenges that need to be overcome, including cellular heterogeneity, immunosuppressive tumor microenvironment (TME), and, in particular, few known cancer-specific targets. Post-translational modifications that differentially occur in malignant cells generate valid cell surface, cancer-specific targets for CAR-T cells. We previously demonstrated that CAR-T cells targeting an aberrant O-glycosylation of MUC1, a common cancer marker associated with changes in cell adhesion, tumor growth, and poor prognosis, could control malignant growth in mouse models. Here, we discuss the field of glycan-directed CAR-T cells and review the different classes of antibodies specific for glycan-targeting, including the generation of high affinity O-glycopeptide antibodies. Finally, we discuss historic and recently investigated glycan targets for CAR-T cells and provide our perspective on how targeting the tumor glycoproteome and/or glycome will improve CAR-T immunotherapy. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Capnography during cardiopulmonary resuscitation: Current evidence and future directions

    Bhavani Shankar Kodali

    2014-01-01

    Full Text Available Capnography continues to be an important tool in measuring expired carbon dioxide (CO 2 . Most recent Advanced Cardiac Life Support (ACLS guidelines now recommend using capnography to ascertain the effectiveness of chest compressions and duration of cardiopulmonary resuscitation (CPR. Based on an extensive review of available published literature, we selected all available peer-reviewed research investigations and case reports. Available evidence suggests that there is significant correlation between partial pressure of end-tidal CO 2 (PETCO 2 and cardiac output that can indicate the return of spontaneous circulation (ROSC. Additional evidence favoring the use of capnography during CPR includes definitive proof of correct placement of the endotracheal tube and possible prediction of patient survival following cardiac arrest, although the latter will require further investigations. There is emerging evidence that PETCO 2 values can guide the initiation of extracorporeal life support (ECLS in refractory cardiac arrest (RCA. There is also increasing recognition of the value of capnography in intensive care settings in intubated patients. Future directions include determining the outcomes based on capnography waveforms PETCO 2 values and determining a reasonable duration of CPR. In the future, given increasing use of capnography during CPR large databases can be analyzed to predict outcomes.

  15. Direct lifts of coupled cell networks

    Dias, A. P. S.; Moreira, C. S.

    2018-04-01

    In networks of dynamical systems, there are spaces defined in terms of equalities of cell coordinates which are flow-invariant under any dynamical system that has a form consistent with the given underlying network structure—the network synchrony subspaces. Given a network and one of its synchrony subspaces, any system with a form consistent with the network, restricted to the synchrony subspace, defines a new system which is consistent with a smaller network, called the quotient network of the original network by the synchrony subspace. Moreover, any system associated with the quotient can be interpreted as the restriction to the synchrony subspace of a system associated with the original network. We call the larger network a lift of the smaller network, and a lift can be interpreted as a result of the cellular splitting of the smaller network. In this paper, we address the question of the uniqueness in this lifting process in terms of the networks’ topologies. A lift G of a given network Q is said to be direct when there are no intermediate lifts of Q between them. We provide necessary and sufficient conditions for a lift of a general network to be direct. Our results characterize direct lifts using the subnetworks of all splitting cells of Q and of all split cells of G. We show that G is a direct lift of Q if and only if either the split subnetwork is a direct lift or consists of two copies of the splitting subnetwork. These results are then applied to the class of regular uniform networks and to the special classes of ring networks and acyclic networks. We also illustrate that one of the applications of our results is to the lifting bifurcation problem.

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

    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) (padvertisements were supplemented with promotion on television and additional websites (September 2012-August 2013) (padvertisements can direct users to evidence-based content at a highly teachable moment--when they are seeking relevant information. © The Author 2014. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Culture, mind, and the brain: current evidence and future directions.

    Kitayama, Shinobu; Uskul, Ayse K

    2011-01-01

    Current research on culture focuses on independence and interdependence and documents numerous East-West psychological differences, with an increasing emphasis placed on cognitive mediating mechanisms. Lost in this literature is a time-honored idea of culture as a collective process composed of cross-generationally transmitted values and associated behavioral patterns (i.e., practices). A new model of neuro-culture interaction proposed here addresses this conceptual gap by hypothesizing that the brain serves as a crucial site that accumulates effects of cultural experience, insofar as neural connectivity is likely modified through sustained engagement in cultural practices. Thus, culture is "embrained," and moreover, this process requires no cognitive mediation. The model is supported in a review of empirical evidence regarding (a) collective-level factors involved in both production and adoption of cultural values and practices and (b) neural changes that result from engagement in cultural practices. Future directions of research on culture, mind, and the brain are discussed.

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

    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.

  19. Direct behavioral and neurophysiological evidence for retronasal olfaction in mice.

    Michelle R Rebello

    Full Text Available The neuroscience of flavor perception is hence becoming increasingly important to understand food flavor perception that guides food selection, ingestion and appreciation. We recently provided evidence that rats can use the retronasal mode of olfaction, an essential element of human flavor perception. We showed that in rats, like humans, odors can acquire a taste. We and others also defined how the input of the olfactory bulb (OB -not functionally imageable in humans- codes retronasal smell in anesthetized rat. The powerful awake transgenic mouse, however, would be a valuable additional model in the study of flavor neuroscience. We used a go/no-go behavioral task to test the mouse's ability to detect and discriminate the retronasal odor amyl acetate. In this paradigm a tasteless aqueous odor solution was licked by water-restricted head-fixed mice from a lick spout. Orthonasal contamination was avoided. The retronasal odor was successfully discriminated by mice against pure distilled water in a concentration-dependent manner. Bulbectomy removed the mice's ability to discriminate the retronasal odor but not tastants. The OB showed robust optical calcium responses to retronasal odorants in these awake mice. These results suggest that mice, like rats, are capable of smelling retronasally. This direct neuro-behavioral evidence establishes the mouse as a useful additional animal model for flavor research.

  20. Silicon Based Direct Methanol Fuel Cells

    Larsen, Jackie Vincent

    The purpose of this project has been to investigate and fabricate small scale Micro Direct Methanol Fuel Cells (μDMFC). They are investigated as a possible alternative for Zinc-air batteries in small size consumer devices such as hearing aids. In such devices the conventional rechargeable batteries...... such as lithium-ion batteries have insufficiently low energy density. Methanol is a promising fuel for such devices due to the high energy density and ease of refueling compared to charging batteries, making μDMFC a suitable replacement energy source. In this Ph.D. dissertation, silicon micro fabrication...... techniques where utilized to build μDMFCs with the purpose of engineering the structures, both on the micro and nano scales in order to realize a high level of control over the membrane and catalyst components. The work presents four different monolithic fuel cell designs. The primary design is based...

  1. Direct FuelCell/Turbine Power Plant

    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

  2. Autonomous Voltage Oscillations in a Direct Methanol Fuel Cell

    Nogueira, Jéssica A.; Peña Arias, Ivonne K.; Hanke-Rauschenbach, Richard; Vidakovic-Koch, Tanja; Varela, Hamilton; Sundmacher, Kai

    2016-01-01

    Proton exchange membrane fuel cells fed with H_2/CO mixtures at the anode have a considerably lower performance than fuel cells fed with pure hydrogen. However, when operated in an autonomous oscillatory regime, the overall voltage loss decreases due to a self-cleaning mechanism. Another molecule, also widely used as feed in the fuel cell and susceptible to kinetic instabilities, is methanol. To the best of our knowledge, there are no reports on autonomous voltage oscillations in the direct methanol fuel cell (DMFC). The purpose of this work was to explore if such instabilities also occur in the DMFC system. Initially, half-cell experiments with a gas diffusion electrode were performed. Then, a DMFC was operated under current control and studied by means of electrochemical impedance spectroscopy. The half-cell measurements revealed that the induction period for oscillations depends on the mass transfer conditions, where on stagnant electrode the induction time was shorter than in the case of forced convection. The DMFC showed also autonomous voltage oscillations above a certain threshold current. The results obtained by electrochemical impedance spectroscopy give evidence of a negative differential resistance in the fuel cell, hitherto not described in the literature, which can be related to the appearance of oscillations during galvanostatic methanol electro-oxidation. These results open the possibility to evaluate the performance of low-temperature fuel cells fed with carbon-containing fuels under oscillatory operating conditions.

  3. FIRST DIRECT EVIDENCE THAT BARIUM DWARFS HAVE WHITE DWARF COMPANIONS

    Gray, R. O.; McGahee, C. E.; Griffin, R. E. M.; Corbally, C. J.

    2011-01-01

    Barium II (Ba) stars are chemically peculiar F-, G-, and K-type objects that show enhanced abundances of s-process elements. Since s-process nucleosynthesis is unlikely to take place in stars prior to the advanced asymptotic giant branch (AGB) stage, the prevailing hypothesis is that each present Ba star was contaminated by an AGB companion which is now a white dwarf (WD). Unless the initial mass ratio of such a binary was fairly close to unity, the receiving star is thus at least as likely to be a dwarf as a giant. So although most known Ba stars appear to be giants, the hypothesis requires that Ba dwarfs be comparably plentiful and moreover that they should all have WD companions. However, despite dedicated searches with the IUE satellite, no WD companions have been directly detected to date among the classical Ba dwarfs, even though some 90% of those stars are spectroscopic binaries, so the contamination hypothesis is therefore presently in some jeopardy. In this paper, we analyze recent deep, near-UV and far-UV Galaxy Evolution Explorer (GALEX) exposures of four of the brightest of the class (HD 2454, 15360, 26367, and 221531), together with archived GALEX data for two newly recognized Ba dwarfs: HD 34654 and HD 114520 (which also prove to be spectroscopic binaries). The GALEX observations of the Ba dwarfs as a group show a significant far-UV excess compared to a control sample of normal F-type dwarfs. We suggest that this ensemble far-UV excess constitutes the first direct evidence that Ba dwarfs have WD companions.

  4. Response of a direct methanol fuel cell to fuel change

    Leo, T.J. [Dpto de Sistemas Oceanicos y Navales- ETSI Navales, Univ. Politecnica de Madrid, Avda Arco de la Victoria s/n, 28040 Madrid (Spain); Raso, M.A.; de la Blanca, E. Sanchez [Dpto de Quimica Fisica I- Fac. CC. Quimicas, Univ. Complutense de Madrid, Avda Complutense s/n, 28040 Madrid (Spain); Navarro, E.; Villanueva, M. [Dpto de Motopropulsion y Termofluidodinamica, ETSI Aeronauticos, Univ. Politecnica de Madrid, Pza Cardenal Cisneros 3, 28040 Madrid (Spain); Moreno, B. [Instituto de Ceramica y Vidrio, Consejo Superior de Investigaciones Cientificas, C/Kelsen 5, Campus de la UAM, 28049 Cantoblanco, Madrid (Spain)

    2010-10-15

    Methanol and ethanol have recently received much attention as liquid fuels particularly as alternative 'energy-vectors' for the future. In this sense, to find a direct alcohol fuel cell that able to interchange the fuel without losing performances in an appreciable way would represent an evident advantage in the field of portable applications. In this work, the response of a in-house direct methanol fuel cell (DMFC) to the change of fuel from methanol to ethanol and its behaviour at different ambient temperature values have been investigated. A corrosion study on materials suitable to fabricate the bipolar plates has been carried out and either 316- or 2205-duplex stainless steels have proved to be adequate for using in direct alcohol fuel cells. Polarization curves have been measured at different ambient temperature values, controlled by an experimental setup devised for this purpose. Data have been fitted to a model taking into account the temperature effect. For both fuels, methanol and ethanol, a linear dependence of adjustable parameters with temperature is obtained. Fuel cell performance comparison in terms of open circuit voltage, kinetic and resistance is established. (author)

  5. Selectivity of Direct Methanol Fuel Cell Membranes

    Antonino S. Aricò

    2015-11-01

    Full Text Available 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.

  6. Selectivity of Direct Methanol Fuel Cell Membranes.

    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).

  7. Direct behavioral evidence for retronasal olfaction in rats.

    Shree Hari Gautam

    Full Text Available 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.

  8. Direct electron transfer based enzymatic fuel cells

    Falk, Magnus; Blum, Zoltan; Shleev, Sergey

    2012-01-01

    In this mini-review we briefly describe some historical developments made in the field of enzymatic fuel cells (FCs), discussing important design considerations taken when constructing mediator-, cofactor-, and membrane-less biological FCs (BFCs). Since the topic is rather extensive, only BFCs utilizing direct electron transfer (DET) reactions on both the anodic and cathodic sides are considered. Moreover, the performance of mostly glucose/oxygen biodevices is analyzed and compared. We also present some unpublished results on mediator-, cofactor-, and membrane-less glucose/oxygen BFCs recently designed in our group and tested in different human physiological fluids, such as blood, plasma, saliva, and tears. Finally, further perspectives for BFC applications are highlighted.

  9. Matlab Source Code for Species Transport through Nafion Membranes in Direct Ethanol, Direct Methanol, and Direct Glucose Fuel Cells

    JH, Summerfield; MW, Manley

    2016-01-01

    A simple simulation of chemical species movement is presented. The species traverse a Nafion membrane in a fuel cell. Three cells are examined: direct methanol, direct ethanol, and direct glucose. The species are tracked using excess proton concentration, electric field strength, and voltage. The Matlab computer code is provided.

  10. Empirical evidence of direct rebound effect in Catalonia

    Freire Gonzalez, Jaume

    2010-01-01

    This paper reviews the empirical literature concerning the direct rebound effect in households; it briefly analyzes the main theoretical and methodological aspects, and finally estimates the magnitude of direct rebound effect for all energy services using electricity in households of Catalonia (Spain) using econometric techniques. The main results show an estimated direct rebound effect of 35% in the short term and 49% in the long term. The existence of a rebound effect reduces the effectiveness of energy efficiency policies.

  11. Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells.

    Strassburg, Sandra; Hodson, Nigel W; Hill, Patrick I; Richardson, Stephen M; Hoyland, Judith A

    2012-01-01

    Mesenchymal stem cell (MSC)-based therapies have been proposed as novel treatments for intervertebral disc (IVD) degeneration. We have previously demonstrated that when MSCs are co-cultured with nucleus pulposus (NP) cells with direct cell-cell contact, they differentiate along the NP lineage and simultaneously stimulate the degenerate NP cell population to regain a normal (non-degenerate) phenotype, an effect which requires cell-cell communication. However, the mechanisms by which NP cells and MSCs interact in this system are currently unclear. Thus, in this study we investigated a range of potential mechanisms for exchange of cellular components or information that may direct these changes, including cell fusion, gap-junctional communication and exchange of membrane components by direct transfer or via microvesicle formation. Flow cytometry of fluorescently labeled MSCs and NP cells revealed evidence of some cell fusion and formation of gapjunctions, although at the three timepoints studied these phenomena were detectable only in a small proportion of cells. While these mechanisms may play a role in cell-cell communication, the data suggests they are not the predominant mechanism of interaction. However, flow cytometry of fluorescently dual-labeled cells showed that extensive bi-directional transfer of membrane components is operational during direct co-culture of MSCs and NP cells. Furthermore, there was also evidence for secretion and internalization of membrane-bound microvesicles by both cell types. Thus, this study highlights bi-directional intercellular transfer of membrane components as a possible mechanism of cellular communication between MSC and NP cells.

  12. Silk Film Topography Directs Collective Epithelial Cell Migration

    Rosenblatt, Mark I.

    2012-01-01

    The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

  13. Direct evidence for T violation in the neutral kaon system

    Adler, R; Angelopoulos, Angelos; Aspostolakis, A; Aslanides, Elie; Backenstoss, Gerhard; Bee, C P; Behnke, O; Benelli, A; Bertin, V; Blanc, F; Bloch, P; Bula, C; Carlson, P J; Carroll, M; Carvalho, J; Cawley, E; Charalambous, S; Chardalas, M; Chardin, G; Chertok, M B; Cody, A; Danielsson, M; Dedoussis, S; Dejardin, M; Derré, J; Duclos, J; Ealet, A; Eckart, B; Eleftheriadis, C; Evangelou, I; Faravel, L; Fassnacht, P; Faure, J L; Felder, C; Ferreira-Marques, R; Fetscher, W; Fidecaro, Maria; Filipcic, A; Francis, D; Fry, J; Gabathuler, Erwin; Gamet, R; Garreta, D; Gerber, H J; Go, A; Guyot, C; Haselden, A; Hayman, P J; Henry-Coüannier, F; Hollander, R W; Hubert, E; Jon-And, K; Kettle, P R; Kochowski, Claude; Kokkas, P; Kreuger, R; Le Gac, R; Leimgruber, F; Liolios, A; Machado, E; Mandic, I; Manthos, N; Marel, Gérard; Mikuz, M; Miller, J; Montanet, François; Nakada, Tatsuya; Onofre, A; Pagels, B; Papadopoulos, I M; Pavlopoulos, P; Pinto da Cunha, J; Policarpo, Armando; Polivka, G; Rickenbach, R; Roberts, B L; Rozaki, E; Ruf, T; Sakelliou, L; Sanders, P; Santoni, C; Sarigiannis, K; Schäfer, M; Schaller, L A; Schopper, A; Schune, P; Soares, A; Tauscher, Ludwig; Thibault, C; Touchard, F; Touramanis, C; Triantis, F A; Van Beveren, E; van Eijk, C W E; Varner, G S; Vlachos, S; Weber, P; Wigger, O; Wolter, M; Yéche, C; Zavrtanik, D; Zimmerman, D

    1995-01-01

    We present the first direct observation of T violation in the neutral kaon system, showing a positive signal with a significance of more than two standard deviations. The result does not rely on the validity of the CPT theorem.

  14. Direct evidence for T violation in the neutral kaon system

    Dejardin, M.; Angelopoulos, A.; Apostolakis, A.; Aslanides, E.; Bertin, V.; Behnke, O.; Benelli, A.

    1995-01-01

    The first direct observation of T violation in the neutral kaon system, is presented showing a positive signal with a significance of more than two standard deviations. The results does not rely on the validity of the CPT theorem. (author)

  15. Development of new membrane materials for direct methanol fuel cells

    Yildirim, M.H.

    2009-01-01

    Development of new membrane materials for direct methanol fuel cells Direct methanol fuel cells (DMFCs) can convert the chemical energy of a fuel directly into electrical energy with high efficiency and low emission of pollutants. DMFCs can be used as the power sources to portable electronic devices

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

    Schiele, Nathan R; Corr, David T [Biomedical Engineering Department, Rensselaer Polytechnic Institute, Troy, NY (United States); Huang Yong [Department of Mechanical Engineering, Clemson University, Clemson, SC (United States); Raof, Nurazhani Abdul; Xie Yubing [College of Nanoscale Science and Engineering, University at Albany, SUNY, Albany, NY (United States); Chrisey, Douglas B, E-mail: schien@rpi.ed, E-mail: chrisd@rpi.ed [Material Science and Engineering Department, Rensselaer Polytechnic Institute, Troy, NY (United States)

    2010-09-15

    Fabrication of cellular constructs with spatial control of cell location ({+-}5 {mu}m) 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. (topical review)

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

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

    2010-01-01

    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. (topical review)

  18. Direct methanol feed fuel cell and system

    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.

  19. Directional differentiation of chicken embryonic stem cells into ...

    Jane

    2011-08-01

    Aug 1, 2011 ... In this study, the differentiation potential of chicken ES cells was investigated ... Key words: Chicken embryonic stem cells, in vitro, directional differentiation, .... synthesized by using the Revert Aid first strand cDNA synthesis kit.

  20. The Direct Methanol Liquid-Feed Fuel Cell

    Halpert, Gerald

    1997-01-01

    Until the early 1990's the idea of a practical direct methanol fuel cell from transportation and other applications was just that, an idea. Several types of fuel cells that operate under near ambient conditions were under development.

  1. Recognizing intentions in infant-directed speech: evidence for universals.

    Bryant, Gregory A; Barrett, H Clark

    2007-08-01

    In all languages studied to date, distinct prosodic contours characterize different intention categories of infant-directed (ID) speech. This vocal behavior likely exists universally as a species-typical trait, but little research has examined whether listeners can accurately recognize intentions in ID speech using only vocal cues, without access to semantic information. We recorded native-English-speaking mothers producing four intention categories of utterances (prohibition, approval, comfort, and attention) as both ID and adult-directed (AD) speech, and we then presented the utterances to Shuar adults (South American hunter-horticulturalists). Shuar subjects were able to reliably distinguish ID from AD speech and were able to reliably recognize the intention categories in both types of speech, although performance was significantly better with ID speech. This is the first demonstration that adult listeners in an indigenous, nonindustrialized, and nonliterate culture can accurately infer intentions from both ID speech and AD speech in a language they do not speak.

  2. Aerosol feed direct methanol fuel cell

    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.

  3. Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

    Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

    2017-07-01

    Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

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

    Jo Richardson

    2016-05-01

    Full Text Available 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.

  5. Direct evidence for inelastic neutron 'acceleration' by 177Lum

    Roig, O.; Meot, V.; Rosse, B.; Belier, G.; Daugas, J.-M.; Morel, P.; Letourneau, A.; Menelle, A.

    2011-01-01

    The inelastic neutron acceleration cross section on the long-lived metastable state of 177 Lu has been measured using a direct method. High-energy neutrons have been detected using a specially designed setup placed on a cold neutron beam extracted from the ORPHEE reactor in Saclay. The 146±19 b inelastic neutron acceleration cross section in the ORPHEE cold neutron flux confirms the high cross section for this process on the 177 Lu m isomer. The deviation from the 258±58 b previously published obtained for a Maxwellian neutron flux at a 323 K temperature could be explained by the presence of a low energy resonance. Resonance parameters are deduced and discussed.

  6. Decompression to altitude: assumptions, experimental evidence, and future directions.

    Foster, Philip P; Butler, Bruce D

    2009-02-01

    Although differences exist, hypobaric and hyperbaric exposures share common physiological, biochemical, and clinical features, and their comparison may provide further insight into the mechanisms of decompression stress. Although altitude decompression illness (DCI) has been experienced by high-altitude Air Force pilots and is common in ground-based experiments simulating decompression profiles of extravehicular activities (EVAs) or astronauts' space walks, no case has been reported during actual EVAs in the non-weight-bearing microgravity environment of orbital space missions. We are uncertain whether gravity influences decompression outcomes via nitrogen tissue washout or via alterations related to skeletal muscle activity. However, robust experimental evidence demonstrated the role of skeletal muscle exercise, activities, and/or movement in bubble formation and DCI occurrence. Dualism of effects of exercise, positive or negative, on bubble formation and DCI is a striking feature in hypobaric exposure. Therefore, the discussion and the structure of this review are centered on those highlighted unresolved topics about the relationship between muscle activity, decompression, and microgravity. This article also provides, in the context of altitude decompression, an overview of the role of denitrogenation, metabolic gases, gas micronuclei, stabilization of bubbles, biochemical pathways activated by bubbles, nitric oxide, oxygen, anthropometric or physiological variables, Doppler-detectable bubbles, and potential arterialization of bubbles. These findings and uncertainties will produce further physiological challenges to solve in order to line up for the programmed human return to the Moon, the preparation for human exploration of Mars, and the EVAs implementation in a non-zero gravity environment.

  7. Recent Advances in High-Performance Direct Methanol Fuel Cells

    Narayanan, S. R.; Chun, W.; Valdez, T. I.; Jeffries-Nakamura, B.; Frank, H.; Surumpudi, S.; Halpert, G.; Kosek, J.; Cropley, C.; La Conti, A. B.; hide

    1996-01-01

    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.

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

    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.

  9. Nursing work directions in Australia: does evidence drive the policy?

    Roche, Michael; Duffield, Christine; Aisbett, Chris; Diers, Donna; Stasa, Helen

    2012-01-01

    A significant body of research has shown a relationship between nurse staffing (in particular, skill-mix: the proportion of Registered Nurses [RNs]) and both morbidity and mortality. This relationship is typically investigated by measuring the incidence of Nursing Sensitive Outcomes (NSOs) under different skill-mix levels. Yet whilst the evidence suggests that richer skill-mix is associated with a lower incidence of NSOs, recent Australian policy reforms have proposed the replacement of Registered Nurses with less qualified staff. The present study sought to examine the relationship between staffing, skill-mix, and incidence of NSOs at two hospitals in one Australian state. The study sought to determine the rate of occurrence of several NSOs, the relationship of skill-mix to that rate, and the number of patients affected per annum. It was found that the current rate of NSOs across wards ranged from 0.17% to 1.05%, and that there was an inverse relationship between the proportion of hours worked by RNs and NSO rates: an increase of 10% in the proportion of hours worked by RNs was linked to a decrease in NSO rates by between 11% and 45%. It was estimated that increasing the RN staffing percentage by 10% would mean 160 fewer adverse outcomes for patients per year across these two hospitals. Importantly, increases in nursing hours overall (without increases in skill-mix) had no significant effect on patient outcomes. These findings challenge current policy recommendations, which propose increasing the number of unregistered staff without increasing skill-mix.

  10. FIRST DIRECT EVIDENCE OF TWO STAGES IN FREE RECALL

    Eugen Tarnow

    2015-12-01

    Full Text Available I find that exactly two stages can be seen directly in sequential free recall distributions. These distributions show that the first three recalls come from the emptying of working memory, recalls 6 and above come from a second stage and the 4th and 5th recalls are mixtures of the two.A discontinuity, a rounded step function, is shown to exist in the fitted linear slope of the recall distributions as the recall shifts from the emptying of working memory (positive slope to the second stage (negative slope. The discontinuity leads to a first estimate of the capacity of working memory at 4-4.5 items. The total recall is shown to be a linear combination of the content of working memory and items recalled in the second stage with 3.0-3.9 items coming from working memory, a second estimate of the capacity of working memory. A third, separate upper limit on the capacity of working memory is found (3.06 items, corresponding to the requirement that the content of working memory cannot exceed the total recall, item by item. This third limit is presumably the best limit on the average capacity of unchunked working memory.The second stage of recall is shown to be reactivation: The average times to retrieve additional items in free recall obey a linear relationship as a function of the recall probability which mimics recognition and cued recall, both mechanisms using reactivation (Tarnow, 2008.

  11. Direct evidence of void passivation in Cu(InGa)(SSe)2 absorber layers

    Lee, Dongho; Kim, Young-Su; Mo, Chan B.; Huh, Kwangsoo; Yang, JungYup; Nam, Junggyu; Baek, Dohyun; Park, Sungchan; Kim, ByoungJune; Kim, Dongseop; Lee, Jaehan; Heo, Sung; Park, Jong-Bong; Kang, Yoonmook

    2015-01-01

    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

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

    Lee, Dongho; Kim, Young-Su; Mo, Chan B.; Huh, Kwangsoo; Yang, JungYup, E-mail: jungyupyang@gmail.com, E-mail: ddang@korea.ac.kr; Nam, Junggyu; Baek, Dohyun; Park, Sungchan; Kim, ByoungJune; Kim, Dongseop [PV Development Team, Energy Solution Business Division, Samsung SDI, 467 Beonyeong-ro, Seobuk-gu, Cheonan-si, Chungcheongnam-do 331-330 (Korea, Republic of); Lee, Jaehan [Core Technology Laboratory, Battery Research Center, Samsung SDI, 130 Samsung-ro, Yeongtong-gu Suwon-si, Gyeonggi-do 443-803 (Korea, Republic of); Heo, Sung; Park, Jong-Bong [Analytical Engineering Group, Samsung Advanced Institute of Technology, 130 Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803 (Korea, Republic of); Kang, Yoonmook, E-mail: jungyupyang@gmail.com, E-mail: ddang@korea.ac.kr [KUKIST Green School, Graduate School of Energy and Environment, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 136-701 (Korea, Republic of)

    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.

  13. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity

    Campana Dario

    2010-10-01

    evidence necessary to support clinical trials utilizing autologous expanded NK cells, both directly and in combination with monoclonal antibodies in future cell-based immunotherapy in select solid tumors.

  14. Cathode-supported hybrid direct carbon fuel cells

    Gil, Vanesa; Gurauskis, Jonas; Deleebeeck, Lisa

    2017-01-01

    The direct conversion of coal to heat and electricity by a hybrid direct carbon fuel cell (HDCFC) is a highly efficient and cleaner technology than the conventional combustion power plants. HDCFC is defined as a combination of solid oxide fuel cell and molten carbonate fuel cell. This work...... investigates cathode-supported cells as an alternative configuration for HDCFC, with better catalytic activity and performance. This study aims to define the best processing route to manufacture highly efficient cathode-supported cells based on La0.75Sr0.25MnO3/yttria-stabilized zirconia infiltrated backbones...

  15. Influence of engineered surface on cell directionality and motility

    Tang, Qing Yuan; Pang, Stella W; Tong, Wing Yin; Shi, Peng; Lam, Yun Wah; Shi, Jue

    2014-01-01

    Control of cell migration is important in numerous key biological processes, and is implicated in pathological conditions such as cancer metastasis and inflammatory diseases. Many previous studies indicated that cell migration could be guided by micropatterns fabricated on cell culture surfaces. In this study, we designed a polydimethylsiloxane cell culture substrate with gratings punctuated by corners and ends, and studied its effects on the behavior of MC3T3-E1 osteoblast cells. MC3T3-E1 cells elongated and aligned with the gratings, and the migration paths of the cells appeared to be guided by the grating pattern. Interestingly, more than 88% of the cells cultured on these patterns were observed to reverse their migration directions at least once during the 16 h examination period. Most of the reversal events occurred at the corners and the ends of the pattern, suggesting these localized topographical features induce an abrupt loss in directional persistence. Moreover, the cell speed was observed to increase temporarily right after each directional reversal. Focal adhesion complexes were more well-established in cells on the angular gratings than on flat surfaces, but the formation of filipodia appeared to be imbalanced at the corners and the ends, possibly leading to the loss of directional persistence. This study describes the first engineered cell culture surface that consistently induces changes in the directional persistence of adherent cells. This will provide an experimental model for the study of this phenomenon and a valuable platform to control the cell motility and directionality, which can be used for cell screening and selection. (paper)

  16. Evidence That Graves' Ophthalmopathy Immunoglobulins Do Not Directly Activate IGF-1 Receptors.

    Marcus-Samuels, Bernice; Krieger, Christine C; Boutin, Alisa; Kahaly, George J; Neumann, Susanne; Gershengorn, Marvin C

    2018-05-01

    Graves' ophthalmopathy (GO) pathogenesis involves thyrotropin (TSH) receptor (TSHR)-stimulating autoantibodies. Whether there are autoantibodies that directly stimulate insulin-like growth factor 1 receptors (IGF-1Rs), stimulating insulin-like growth factor receptor antibodies (IGFRAbs), remains controversial. This study attempted to determine whether there are stimulating IGFRAbs in patients with GO. Immunoglobulins (Igs) were purified from normal volunteers (NV-Igs) and patients with GO (GO-Igs). The effects of TSH, IGF-1, NV-Igs, and GO-Igs on pAKT and pERK1/2, members of pathways used by IGF-1R and TSHR, were compared in orbital fibroblasts from GO patients (GOFs) and U2OS-TSHR cells overexpressing TSHRs, and U2OS cells that express TSHRs at very low endogenous levels. U2OS-TSHR and U2OS cells were used because GOFs are not easily manipulated using molecular techniques such as transfection, and U2OS cells because they express TSHRs at levels that do not measurably stimulate signaling. Thus, comparing U2OS-TSHR and U2OS cells permits specifically distinguishing signaling mediated by the TSHR and IGF-1R. In GOFs, all GO-Igs stimulated pERK1/2 formation and 69% stimulated pAKT. In U2OS-TSHR cells, 15% of NV-IGs and 83% of GO-Igs stimulated increases in pERK1/2, whereas all NV-Igs and GO-Igs stimulated increases in pAKT. In U2OS cells, 70% of GO-Igs stimulated small increases in pAKT. Knockdown of IGF-1R caused a 65 ± 6.3% decrease in IGF-1-stimulated pAKT but had no effect on GO-Igs stimulation of pAKT. Thus, GO-Igs contain factor(s) that stimulate pAKT formation. However, this factor(s) does not directly activate IGF-1R. Based on the findings analyzing these two signaling pathways, it is concluded there is no evidence of stimulating IGFRAbs in GO patients.

  17. Cell fate in the Arabidopsis root meristem determined by directional signalling.

    van den Berg, C; Willemsen, V; Hage, W; Weisbeek, P; Scheres, B

    1995-11-02

    Postembryonic development in plants is achieved by apical meristems. Surgical studies and clonal analysis have revealed indirectly that cells in shoot meristems have no predictable destiny and that position is likely to play a role in the acquisition of cell identity. In contrast to animal systems, there has been no direct evidence for inductive signalling in plants until now. Here we present evidence for such signalling using laser ablation of cells in the root meristem of Arabidopsis thaliana. Although these cells show rigid clonal relationships, we now demonstrate that it is positional control that is most important in the determination of cell fate. Positional signals can be perpetuated from more mature to initial cells to guide the pattern of meristem cell differentiation. This offers an alternative to the general opinion that meristems are the source of patterning information.

  18. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    Cheng Cui

    2013-11-01

    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

  19. Extending EV Range with Direct Methanol Fuel Cells

    Steckmann, Kai

    2009-01-01

    Electric cars are the vehicles of the future, and there is a proven hybrid system for extending their mileage. Direct methanol fuel cells (DMFCs) provide safe, lightweight, onboard battery charging that can free car owners from worry about running out of power. The hybrid system includes a DMFC fuel cell, fuel cell cartridge and electric vehicle batteries. The fuel cell operates almost silently with virtually no exhaust, it is immune to extreme weather and the convenient fuel cartridges featu...

  20. Stem cell monitoring with a direct or indirect labeling method

    Kim, Min Hwan; Lee, Yong Jin [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul (Korea, Republic of)

    2016-12-15

    The molecular imaging techniques allow monitoring of the transplanted cells in the same individuals over time, from early localization to the survival, migration, and differentiation. Generally, there are two methods of stem cell labeling: direct and indirect labeling methods. The direct labeling method introduces a labeling agent into the cell, which is stably incorporated or attached to the cells prior to transplantation. Direct labeling of cells with radionuclides is a simple method with relatively fewer adverse events related to genetic responses. However, it can only allow short-term distribution of transplanted cells because of the decreasing imaging signal with radiodecay, according to the physical half-lives, or the signal becomes more diffuse with cell division and dispersion. The indirect labeling method is based on the expression of a reporter gene transduced into the cell before transplantation, which is then visualized upon the injection of an appropriate probe or substrate. In this review, various imaging strategies to monitor the survival and behavior change of transplanted stem cells are covered. Taking these new approaches together, the direct and indirect labeling methods may provide new insights on the roles of in vivo stem cell monitoring, from bench to bedside.

  1. X mapping in man: evidence against direct measurable linkage between ocular albinism and deutan colour blindness.

    Pearce, W G; Sanger, R

    1976-01-01

    A Newfoundland kindred in which ocular albinism and deutan colour blindness are segregating provides strong evidence against the loci for these two X-borne characters being within direct measurable distance of each other. PMID:1085370

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

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

    2013-01-01

    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....... 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...

  3. Sulfonated poly(ether ether ketone) based membranes for direct ethanol fuel cells

    Roelofs, K.S.

    2010-01-01

    The decreasing availability of fossil fuels and the increasing impact of greenhouse gases on the environment lead to an extensive development of more efficient or renewable energy sources. The direct alcohol fuel cell (DAFC) as a portable energy source is a promising and fast growing technology which meets these demands. Up to now, methanol is mostly studied as a fuel for these devices, however, applying ethanol has some evident advantages over methanol. The major challenges in direct ethanol...

  4. Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil.

    Phelps, Laura E; Peuler, Jacob D

    2010-01-01

    Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARalpha). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPAR alpha may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved. Rapid decreases in arterial pressure following bolus intravenous injections of bezafibrate strongly suggest they may relax arterial smooth muscle directly. But since bezafibrate is highly susceptible to photodegradation in aqueous media, it has never been critically tested for this possibility in vitro with isolated arterial smooth muscle preparations. Accordingly, we tested gemfibrozil which is resistant to photodegradation. We examined it over a therapeutically-relevant range (50-400 microM) for both acute and delayed relaxant effects on contractions of the isolated rat tail artery; contractions induced by either depolarizing its smooth muscle cell membranes with high potassium or stimulating its membrane-bound receptors with norepinephrine and arginine-vasopressin. We also examined these same gemfibrozil levels for effects on spontaneously-occurring phasic rhythmic contractile activity, typically not seen in arteries under in vitro conditions but commonly exhibited by smooth muscle of uterus, duodenum and bladder. We found that gemfibrozil significantly relaxed all induced forms of contraction in the rat tail artery, acutely at the higher test levels and after a delay of a few hours at the lower test levels. The highest test level of gemfibrozil (400 microM) also completely abolished spontaneously-occurring contractile activity of the isolated uterus and duodenum and markedly suppressed it in the bladder. This is the first evidence that a fibrate drug can directly relax smooth muscle contractions, either induced by various contractile agents or

  5. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

    Xiao, Fei; Fofana, Isabel; Heydmann, Laura

    2014-01-01

    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies....... In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV...... genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host...

  6. The JPL Direct Methanol Liquid-feed PEM Fuel Cell

    Halpert, G.; Surampudi, S.

    1994-01-01

    Recently, there has been a breakthrough in fuel cell technology in the Energy Storage Systems Group at the Jet Propulsion Laboratory with the develpment of a direct methanol, liquid-feed, solid polymer electrolyte membrane (PEM) fuel cell... The methanol liquid-feed, solid polymer electrolyte (PEM) design has numerous system level advantages over the gas-feed design. These include:...

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

    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.

  8. Modeling and Simulation of the Direct Methanol Fuel Cell

    Wohr, M.; Narayanan, S. R.; Halpert, G.

    1996-01-01

    From intro.: The direct methanol liquid feed fuel cell uses aqueous solutions of methanol as fuel and oxygen or air as the oxidant and uses an ionically conducting polymer membrane such as Nafion(sup r)117 and the electrolyte. This type of direct oxidation cell is fuel versatile and offers significant advantages in terms of simplicity of design and operation...The present study focuses on the results of a phenomenological model based on current understanding of the various processed operating in these cells.

  9. Extracellular matrix components direct porcine muscle stem cell behavior

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

    2010-01-01

    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.

  10. Extracellular matrix components direct porcine muscle stem cell behavior

    Wilschut, Karlijn J. [Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht (Netherlands); Haagsman, Henk P. [Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht (Netherlands); Roelen, Bernard A.J., E-mail: b.a.j.roelen@uu.nl [Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht (Netherlands)

    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. Macroscopic Modeling of Transport Phenomena in Direct Methanol Fuel Cells

    Olesen, Anders Christian

    An increasing need for energy efficiency and high energy density has sparked a growing interest in direct methanol fuel cells for portable power applications. This type of fuel cell directly generates electricity from a fuel mixture consisting of methanol and water. Although this technology...... surpasses batteries in important areas, fundamental research is still required to improve durability and performance. Particularly the transport of methanol and water within the cell structure is difficult to study in-situ. A demand therefore exist for the fundamental development of mathematical models...... for studying their transport. In this PhD dissertation the macroscopic transport phenomena governing direct methanol fuel cell operation are analyzed, discussed and modeled using the two-fluid approach in the computational fluid dynamics framework of CFX 14. The overall objective of this work is to extend...

  12. Direct evidence of impaired neuronal Na/K-ATPase pump function in alternating hemiplegia of childhood.

    Simmons, Christine Q; Thompson, Christopher H; Cawthon, Bryan E; Westlake, Grant; Swoboda, Kathryn J; Kiskinis, Evangelos; Ess, Kevin C; George, Alfred L

    2018-03-19

    Mutations in ATP1A3 encoding the catalytic subunit of the Na/K-ATPase expressed in mammalian neurons cause alternating hemiplegia of childhood (AHC) as well as an expanding spectrum of other neurodevelopmental syndromes and neurological phenotypes. Most AHC cases are explained by de novo heterozygous ATP1A3 mutations, but the fundamental molecular and cellular consequences of these mutations in human neurons are not known. In this study, we investigated the electrophysiological properties of neurons generated from AHC patient-specific induced pluripotent stem cells (iPSCs) to ascertain functional disturbances underlying this neurological disease. Fibroblasts derived from two subjects with AHC, a male and a female, both heterozygous for the common ATP1A3 mutation G947R, were reprogrammed to iPSCs. Neuronal differentiation of iPSCs was initiated by neurogenin-2 (NGN2) induction followed by co-culture with mouse glial cells to promote maturation of cortical excitatory neurons. Whole-cell current clamp recording demonstrated that, compared with control iPSC-derived neurons, neurons differentiated from AHC iPSCs exhibited a significantly lower level of ouabain-sensitive outward current ('pump current'). This finding correlated with significantly depolarized potassium equilibrium potential and depolarized resting membrane potential in AHC neurons compared with control neurons. In this cellular model, we also observed a lower evoked action potential firing frequency when neurons were held at their resting potential. However, evoked action potential firing frequencies were not different between AHC and control neurons when the membrane potential was clamped to -80 mV. Impaired neuronal excitability could be explained by lower voltage-gated sodium channel availability at the depolarized membrane potential observed in AHC neurons. Our findings provide direct evidence of impaired neuronal Na/K-ATPase ion transport activity in human AHC neurons and demonstrate the potential

  13. Directional Cell Migration in Response to Repeated Substratum Stretching

    Okimura, Chika; Iwadate, Yoshiaki

    2017-10-01

    Crawling migration plays an essential role in a variety of biological phenomena, including development, wound healing, and immune system function. Migration properties such as anterior-posterior polarity, directionality, and velocity are regulated not only by the reception of a chemoattractant but also by sensing mechanical inputs from the external environment. In this review, we describe the mechanical response of migrating cells, particularly under repeated stretching of the elastic substratum, highlighting the fact that there appear to be two independent mechanosensing systems that generate the polarity needed for migration. Cells that have no stress fibers, such as Dictyostelium cells and neutrophil-like differentiated HL-60 cells, migrate perpendicular to the stretching direction via myosin II localization. Cells that do possess stress fibers, however, such as fish keratocytes, migrate parallel to the stretching via a stress-fiber-dependent process.

  14. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

    Hidehiko Takigawa

    2017-05-01

    Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

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

    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).

  16. Left or right? Directions to stem cell engraftment : Directions to stem cell engraftment

    Belderbos, Mirjam E; Bystrykh, Leonid; de Haan, Gerald

    In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20171341) use genetic barcoding of macaque hematopoietic stem cells to demonstrate that, after transplantation, HSCs are very asymmetrically distributed and uncover a thymus-independent pathway for mature T cell production in the bone

  17. A map of directional genetic interactions in a metazoan cell.

    Fischer, Bernd; Sandmann, Thomas; Horn, Thomas; Billmann, Maximilian; Chaudhary, Varun; Huber, Wolfgang; Boutros, Michael

    2015-03-06

    Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.

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

    Ernest, J.B. [Fluor Daniel, Inc., Irvine, CA (United States); Ghezel-Ayagh, H.; Kush, A.K. [Fuel Cell Engineering, Danbury, CT (United States)

    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.

  19. Direct Coal Oxidation in Modified Solid Oxide Fuel Cells

    Deleebeeck, Lisa; Gil, Vanesa; Ippolito, Davide

    2015-01-01

    Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon-carbonate s......Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon......-carbonate slurry or anode layer. The nature of the coal affects both open circuit voltage and power output. Highest OCV and power densities were observed for bituminous coal and by adding manganese oxide or praseodymium-doped ceria to the carbon/carbonate mixture. Comparing the carbon black fueled performance...... bituminous coal (73 mW/cm2). © 2015 ECS - The Electrochemical Society...

  20. Direct Coal Oxidation in Modified Solid Oxide Fuel Cells

    Deleebeeck, Lisa; Gil, Vanesa; Ippolito, Davide

    2017-01-01

    Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon-carbonate s......Hybrid direct carbon fuel cells employ a classical solid oxide fuel cell together with carbon dispersed in a carbonate melt on the anode side. In a European project, the utilization of various coals has been investigated with and without addition of an oxidation catalyst to the carbon......-carbonate slurry or anode layer. The nature of the coal affects both open circuit voltage and power output. Highest OCV and power densities were observed for bituminous coal and by adding manganese oxide or praseodymium-doped ceria to the carbon/carbonate mixture. Comparing the carbon black fueled performance...... bituminous coal (73 mW/cm2)....

  1. A Direct DME High Temperature PEM Fuel Cell

    Vassiliev, Anton; Jensen, Jens Oluf; Li, Qingfeng

    2012-01-01

    Dimethyl ether (DME) has been identified as an alternative to methanol for use in direct fuel cells. It combines the advantages of hydrogen in terms of pumpless fuel delivery and high energy density like methanol, but without the toxicity of the latter. The performance of a direct dimethyl ether...... fuel cell suffers greatly from the very low DME-water miscibility. To cope with the problem polybenzimidazole (PBI) based membrane electrode assemblies (MEAs) have been made and tested in a vapor fed system. PtRu on carbon has been used as anode catalyst and air at ambient pressure was used as oxidant...

  2. Head direction cell activity in mice: robust directional signal depends on intact otolith organs

    Yoder, Ryan M.; Taube, Jeffrey S.

    2009-01-01

    The head direction (HD) cell signal is a representation of an animal's perceived directional heading with respect to its environment. This signal appears to originate in the vestibular system, which includes the semicircular canals and otolith organs. Preliminary studies indicate the semicircular canals provide a necessary component of the HD signal, but involvement of otolithic information in the HD signal has not been tested. The present study was designed to determine the otolithic contribution to the HD signal, as well as to compare HD cell activity of mice to that of rats. HD cell activity in the anterodorsal thalamus was assessed in wild-type C57BL/6J and otoconia-deficient tilted mice during locomotion within a cylinder containing a prominent visual landmark. HD cell firing properties in C57BL/6J mice were generally similar to those in rats. However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant control of the HD signal in 36% of the sessions. In darkness, directional firing became unstable during 42% of the sessions, but landmark control was not associated with HD signal stability in darkness. HD cells were identified in tilted mice, but directional firing properties were not as robust as those of C57BL/6J mice. Most HD cells in tilted mice were controlled by landmark rotation, but showed substantial signal degradation across trials. These results support current models that suggest otolithic information is involved in the perception of directional heading. Furthermore, compared to rats, the HD signal in mice appears to be less reliably anchored to prominent environmental cues. PMID:19176815

  3. Heading-vector navigation based on head-direction cells and path integration.

    Kubie, John L; Fenton, André A

    2009-05-01

    Insect navigation is guided by heading vectors that are computed by path integration. Mammalian navigation models, on the other hand, are typically based on map-like place representations provided by hippocampal place cells. Such models compute optimal routes as a continuous series of locations that connect the current location to a goal. We propose a "heading-vector" model in which head-direction cells or their derivatives serve both as key elements in constructing the optimal route and as the straight-line guidance during route execution. The model is based on a memory structure termed the "shortcut matrix," which is constructed during the initial exploration of an environment when a set of shortcut vectors between sequential pairs of visited waypoint locations is stored. A mechanism is proposed for calculating and storing these vectors that relies on a hypothesized cell type termed an "accumulating head-direction cell." Following exploration, shortcut vectors connecting all pairs of waypoint locations are computed by vector arithmetic and stored in the shortcut matrix. On re-entry, when local view or place representations query the shortcut matrix with a current waypoint and goal, a shortcut trajectory is retrieved. Since the trajectory direction is in head-direction compass coordinates, navigation is accomplished by tracking the firing of head-direction cells that are tuned to the heading angle. Section 1 of the manuscript describes the properties of accumulating head-direction cells. It then shows how accumulating head-direction cells can store local vectors and perform vector arithmetic to perform path-integration-based homing. Section 2 describes the construction and use of the shortcut matrix for computing direct paths between any pair of locations that have been registered in the shortcut matrix. In the discussion, we analyze the advantages of heading-based navigation over map-based navigation. Finally, we survey behavioral evidence that nonhippocampal

  4. Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

    Romuald Polczyk

    2016-01-01

    Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence ...

  5. Evidence for differentiation of cell wall poles in Bacillus subtilis

    Sonnenfeld, E.M.

    1985-01-01

    Previous data have suggested that the chromosome of Bacillus subtilis was found to the cell surface at polar regions. A significant corollary of DNA attachment to cell poles is the role of the cell wall in chromosome segregation. This project was mainly concerned with visualizing the DNA-cell wall association through autoradiography. The origin and terminus of replication were labelled with ( 3 H)-thymidine using a temperature-sensitive DNA initiation mutant. It was found that most of the radioactivity was associated with cell poles. Ultrastructural analyses of cell walls stained with dilute cationized ferritin showed that the polar area contained a site of dense electronegativity. It is not immediately apparent why cell wall poles would contain an area with a high concentration of negative charge. This finding may be related to the cell pole functioning as the site of chromosome attachment. An additional observation encountered in this study was that cell wall exhibited asymmetry with regard to negative charge, the outside surface being more electronegative than the inside. A significant consequence of this finding is that both teichoic acid and muramyl peptides are situated perpendicularly to the cell surface. This favored arrangement may facilitate cell separation during the division process due to opposition of like charges at septa. The results of this work provide further convincing evidence that the cell wall of B. subtilis is differentiated

  6. Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a direct role.

    Panariti, A; Baglole, C J; Sanchez, V; Eidelman, D H; Hussain, S; Olivenstein, R; Martin, J G; Hamid, Q

    2018-04-01

    Bronchial vascular remodelling may contribute to the severity of airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated with the most severe asthmatic phenotype but whether it might contribute to vascular remodelling is uncertain. To assess vascular remodelling in severe asthma and whether IL-17A directly or indirectly may cause endothelial cell activation and angiogenesis. Bronchial vascularization was quantified in asthmatic subjects, COPD and healthy subjects together with the number of IL-17A + cells as well as the concentration of angiogenic factors in the sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and endothelial permeability was assessed directly on primary human lung microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and airway smooth muscle cells (ASMC) after IL-17A stimulation. Severe asthmatics have increased vascularity compared to the other groups, which correlates positively with the concentrations of angiogenic factors in sputum. Interestingly, we demonstrated that increased bronchial vascularity correlates positively with the number of subepithelial IL-17A + cells. However IL-17A had no direct effect on HMVEC-L function but it enhanced endothelial tube formation and cell migration through the production of angiogenic factors by NHBE and ASMC. Our results shed light on the role of IL-17A in vascular remodelling, most likely through stimulating the synthesis of other angiogenic factors. Knowledge of these pathways may aid in the identification of new therapeutic targets. © 2018 John Wiley & Sons Ltd.

  7. Direct hydrogen fuel cell systems for hybrid vehicles

    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.

  8. hydrogel membrane as electrolyte for direct borohydride fuel cells

    A direct borohydride fuel cell (DBFC) employing a poly (vinyl alcohol) hydrogel membrane electrolyte (PHME) is reported. The DBFC employs an AB5 Misch metal alloy as anode and a goldplated stainless steel mesh as cathode in conjunction with aqueous alkaline solution of sodium borohydride as fuel and aqueous ...

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

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

    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

  10. The Pore Structure of Direct Methanol Fuel Cell Electrodes

    Lund, Peter Brilner

    2005-01-01

    The pore structure and morphology of direct methanol fuel cell electrodes are characterized using mercury intrusion porosimetry and scanning electron microscopy. It is found that the pore size distributions of printed primer and catalyst layers are largely dictated by the powders used to make...

  11. Directed neuronal differentiation of human embryonic stem cells

    Noggle Scott A

    2003-10-01

    Full Text Available Abstract Background We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs to neural precursors and neurons. HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII. Results A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7–10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons. Conclusion This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.

  12. Recent progresses in materials for the direct methanol fuel cell

    Lamy, C; Leger, J M [Centre National de la Recherche Scientifique (CNRS), 86 - Poitiers (France)

    1998-12-31

    Research programs are being conducted worldwide to develop a clean, zero emissions electric vehicle. However, even with the most advanced batteries, such as nickel/metal hydride, or lithium ion batteries, the driving range is limited and the recharging time is long. Only fuel cells which can convert chemical energy directly into electrical energy can compete with internal combustion engines. This paper reviewed the recent progress made in the development of a direct methanol fuel cell using the concept developed for the proton exchange membrane fuel cell (PEMFC). It was noted that the electrode materials, at the methanol anode and oxygen cathode need to be improved by using multifunctional electrocatalysts. The development of new temperature resistant proton exchange membranes with good ionic conductivity and low methanol cross-over, which resulted from the need to increase operating temperatures above 100 degrees C was also reviewed. 35 refs., 1 tab., 2 figs.

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

    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.

  14. Manipulating directional cell motility using intracellular superparamagnetic nanoparticles

    Bradshaw, Michael; Clemons, Tristan D.; Ho, Diwei; Gutiérrez, Lucía; Lázaro, Francisco J.; House, Michael J.; St. Pierre, Timothy G.; Fear, Mark W.; Wood, Fiona M.; Iyer, K. Swaminathan

    2015-03-01

    This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications.This study investigated the ability for magnetic nanoparticles to influence cellular migration in the presence of an external magnetic field. We found that the direction of migrating keratinocytes can be controlled and the migration speed of fibroblasts can be increased with the internalisation of these nanoparticles in the presence of a magnetic field. The possibility of shepherding cells towards a region of interest through the use of internalized nanoparticles is an attractive prospect for cell tracking, cell therapies, and tissue engineering applications. Electronic supplementary information (ESI) available: Nanoparticle characterisation, supporting experimental data, video time course study of cellular uptake of the nanoparticles and complete experimental details are all provided in the ESI. See DOI: 10.1039/c4nr06594h

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

    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.

  16. Pt -based anode catalysts for direct ethanol fuel cells

    Hoyos, Bibian; Sanchez, Carlos; Gonzalez, Javier

    2007-01-01

    In this work it is studied the electro-catalytic behavior of pure platinum and platinum-based alloys with Ru, Sn, Ir, and Os supported on carbon to the ethanol electro-oxidation in aims to develop anodic catalysts for direct ethanol fuel cells, additionally, porous electrodes and membrane electrode assemblies were built for proton exchange membrane fuel cells in which the electrodes were tested. Catalysts characterization was made by cyclic voltammetry whereas the fuel cells behavior tests were made by current-potential polarization curves. in general, all alloys show a lower on-set reaction potential and a higher catalytic activity than pure platinum. However, in the high over potential zone, pure platinum has higher catalytic activity than the alloys. In agreement with these results, the alloys studied here could be useful in fuel cells operating on moderated and low current

  17. Allosteric conformational barcodes direct signaling in the cell.

    Nussinov, Ruth; Ma, Buyong; Tsai, Chung-Jung; Csermely, Peter

    2013-09-03

    The cellular network is highly interconnected. Pathways merge and diverge. They proceed through shared proteins and may change directions. How are cellular pathways controlled and their directions decided, coded, and read? These questions become particularly acute when we consider that a small number of pathways, such as signaling pathways that regulate cell fates, cell proliferation, and cell death in development, are extensively exploited. This review focuses on these signaling questions from the structural standpoint and discusses the literature in this light. All co-occurring allosteric events (including posttranslational modifications, pathogen binding, and gain-of-function mutations) collectively tag the protein functional site with a unique barcode. The barcode shape is read by an interacting molecule, which transmits the signal. A conformational barcode provides an intracellular address label, which selectively favors binding to one partner and quenches binding to others, and, in this way, determines the pathway direction, and, eventually, the cell's response and fate. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    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.

  19. Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate

    von Erlach, Thomas C.; Bertazzo, Sergio; Wozniak, Michele A.; Horejs, Christine-Maria; Maynard, Stephanie A.; Attwood, Simon; Robinson, Benjamin K.; Autefage, Hélène; Kallepitis, Charalambos; del Río Hernández, Armando; Chen, Christopher S.; Goldoni, Silvia; Stevens, Molly M.

    2018-03-01

    Cell size and shape affect cellular processes such as cell survival, growth and differentiation1-4, thus establishing cell geometry as a fundamental regulator of cell physiology. The contributions of the cytoskeleton, specifically actomyosin tension, to these effects have been described, but the exact biophysical mechanisms that translate changes in cell geometry to changes in cell behaviour remain mostly unresolved. Using a variety of innovative materials techniques, we demonstrate that the nanostructure and lipid assembly within the cell plasma membrane are regulated by cell geometry in a ligand-independent manner. These biophysical changes trigger signalling events involving the serine/threonine kinase Akt/protein kinase B (PKB) that direct cell-geometry-dependent mesenchymal stem cell differentiation. Our study defines a central regulatory role by plasma membrane ordered lipid raft microdomains in modulating stem cell differentiation with potential translational applications.

  20. Manufacturing technologies for direct methanol fuel cells (DMFCs)

    Gluesen, Andreas; Mueller, Martin; Kimiaie, Nicola; Konradi, Irene; Mergel, Juergen; Stolten, Detlef [Forschungszentrum Juelich (Germany). Inst. of Energy Research - IEF-3: Fuel Cells

    2010-07-01

    Fuel cell research is focussing on increasing power density and lifetime and reducing costs of the whole fuel cell system. In order to reach these aims, it is necessary to develop appropriately designed components outgoing from high quality materials, a suitable manufacturing process and a well balanced system. To make use of the advantages that can be obtained by developing production technology, we are mainly improving the coating and assembling techniques for polymer electrolyte fuel cells, especially Direct Methanol Fuel Cells (DMFCs). Coating is used for making fuel cell electrodes as well as highly conductive contacts. Assembling is used to join larger components like membrane electrode assemblies (MEAs) and bipolar units consisting of flow fields and the separator plate, as well as entire stacks. On the one hand a reproducible manufacturing process is required to study fine differences in fuel cell performance affected by new materials or new designs. On the other hand a change in each parameter of the manufacturing process itself can change product properties and therefore affect fuel cell performance. As a result, gas diffusion electrodes (GDEs) are now produced automatically in square-meter batches, the hot-pressing of MEAs is a fully automated process and by pre-assembling the number of parts that have to be assembled in a stack was reduced by a factor of 10. These achievements make DMFC manufacturing more reproducible and less error-prone. All these and further developments of manufacturing technology are necessary to make DMFCs ready for the market. (orig.)

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

    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.

  2. Magnetically insulated fission electric cells for direct energy conversion

    Slutz, S.A.; Seidel, D.B.; Lipinski, R.J.; Rochau, G.E.; Brown, L.C.

    2003-01-01

    The principles of fission electric cells are reviewed. A detailed Monte Carlo model of the efficiency of a fission electric cell is presented and a theory of magnetically insulated fission electric cells (MIFECs) is developed. It is shown that the low operating voltages observed in previous MIFEC experiments were due to nonoptimal magnetic field profiles. Improved magnetic field profiles are presented. It is further shown that the large electric field present in a MIFEC limits the structure of the cathode and can lead to a displacement instability of the cathode toward the anode. This instability places constraints on the number of cells that can be strung together without some external cathode support. The large electric field stress also leads to electrical surface breakdown of the cathode. It is shown that this leads to the formation of a virtual cathode resulting in geometry constraints for spherical cells. Finally it is shown that the requirements of magnetic insulation and high efficiency leads to very low average density of the fissile material. Thus a reactor using fission electric cells for efficient direct energy conversion will be large and require a very large number of cells. This could be mitigated somewhat by the use of exotic fuels

  3. Direction of Wolf-Rayet stars in a very powerful far-infrared galaxy - Direct evidence for a starburst

    Armus, L.; Heckman, T.M.; Miley, G.K.

    1988-01-01

    Spectra covering the wavelength range 4476-7610 A are presented for the powerful far-infrared galaxy IRAS 01003-2238. The broad emission band centered at a rest wavelength of roughly 4660 A, and other broad weaker features are interpreted, as arising from the combined effect of approximately 100,000 late Wolf-Rayet stars of the WN subtype. This represents perhaps the most direct evidence to date for the presence of a large number of hot massive stars in the nucleus of a very powerful far-infrared galaxy. The high number of Wolf-Rayet stars in relation to the number of O-type stars may be interpreted as arguing against continuous steady state star formation in 01003-2238, in favor of a recent burst of star formation occurring approximately 100 million yrs ago. 24 references

  4. Direct dimethyl ether high temperature polymer electrolyte membrane fuel cells

    Vassiliev, Anton; Jensen, Jens Oluf; Li, Qingfeng

    and suffers from low DME solubility in water. When the DME - water mixture is fed as vapour miscibility is no longer a problem. The increased temperature is more beneficial for the kinetics of the direct oxidation of DME than of methanol. The Open Circuit Voltage (OCV) with DME operation was 50 to 100 m......A high temperature polybenzimidazole (PBI) polymer fuel cell was fed with dimethyl ether (DME) and water vapour mixture on the anode at ambient pressure with air as oxidant. A peak power density of 79 mW/cm2 was achieved at 200°C. A conventional polymer based direct DME fuel cell is liquid fed......V higher than that of methanol, indicating less fuel crossover....

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

    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.

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

    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. © 2010 American Academy of Forensic Sciences.

  7. Direct methanol feed fuel cell with reduced catalyst loading

    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.

  8. Directed cell migration in the presence of obstacles

    Grima Ramon

    2007-01-01

    Full Text Available Abstract Background Chemotactic movement is a common feature of many cells and microscopic organisms. In vivo, chemotactic cells have to follow a chemotactic gradient and simultaneously avoid the numerous obstacles present in their migratory path towards the chemotactic source. It is not clear how cells detect and avoid obstacles, in particular whether they need a specialized biological mechanism to do so. Results We propose that cells can sense the presence of obstacles and avoid them because obstacles interfere with the chemical field. We build a model to test this hypothesis and find that this naturally enables efficient at-a-distance sensing to be achieved with no need for a specific and active obstacle-sensing mechanism. We find that (i the efficiency of obstacle avoidance depends strongly on whether the chemotactic chemical reacts or remains unabsorbed at the obstacle surface. In particular, it is found that chemotactic cells generally avoid absorbing barriers much more easily than non-absorbing ones. (ii The typically low noise in a cell's motion hinders the ability to avoid obstacles. We also derive an expression estimating the typical distance traveled by chemotactic cells in a 3D random distribution of obstacles before capture; this is a measure of the distance over which chemotaxis is viable as a means of directing cells from one point to another in vivo. Conclusion Chemotactic cells, in many cases, can avoid obstacles by simply following the spatially perturbed chemical gradients around obstacles. It is thus unlikely that they have developed specialized mechanisms to cope with environments having low to moderate concentrations of obstacles.

  9. Reactivity descriptors for direct methanol fuel cell anode catalysts

    Ferrin, Peter; Nilekar, Anand Udaykumar; Greeley, Jeff

    2008-01-01

    oxidation to CO2 are investigated: an indirect mechanism that goes through a CO intermediate and a direct mechanism where methanol is oxidized to CO2 without the formation of a CO intermediate. For the direct mechanism, we find that, because of CO poisoning, only a small current will result on all non......We have investigated the anode reaction in direct methanol fuel cells using a database of adsorption free energies for 16 intermediates on 12 close-packed transition metal surfaces calculated with periodic, self-consistent, density functional theory (DFT-GGA). This database, combined with a simple...... electrokinetic model of the methanol electrooxidation reaction, yields mechanistic insights that are consistent with previous experimental and theoretical studies on Pt, and extends these insights to a broad spectrum of other transition metals. In addition, by using linear scaling relations between...

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

    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.

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

    Masel, Richard I [Champaign, IL; Zhu, Yimin [Urbana, IL; Kahn, Zakia [Palatine, IL; Man, Malcolm [Vancouver, CA

    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.

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

    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.

  13. Performance evaluation of direct methanol fuel cells for portable applications

    Rashidi, R.; Dincer, I.; Naterer, G.F. [Faculty of Engineering and Applied Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, Ontario (Canada); Berg, P. [Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, Ontario (Canada)

    2009-02-15

    This study examines the feasibility of powering a range of portable devices with a direct methanol fuel cell (DMFC). The analysis includes a comparison between a Li-ion battery and DMFC to supply the power for a laptop, camcorder and a cell phone. A parametric study of the systems for an operational period of 4 years is performed. Under the assumptions made for both the Li-ion battery and DMFC system, the battery cost is lower than the DMFC during the first year of operation. However, by the end of 4 years of operational time, the DMFC system would cost less. The weight and cost comparisons show that the fuel cell system occupies less space than the battery to store a higher amount of energy. The weight of both systems is almost identical. Finally, the CO{sub 2} emissions can be decreased by a higher exergetic efficiency of the DMFC, which leads to improved sustainability. (author)

  14. High performance direct methanol fuel cell with thin electrolyte membrane

    Wan, Nianfang

    2017-06-01

    A high performance direct methanol fuel cell is achieved with thin electrolyte membrane. 320 mW cm-2 of peak power density and over 260 mW cm-2 at 0.4 V are obtained when working at 90 °C with normal pressure air supply. It is revealed that the increased anode half-cell performance with temperature contributes primarily to the enhanced performance at elevated temperature. From the comparison of iR-compensated cathode potential of methanol/air with that of H2/air fuel cell, the impact of methanol crossover on cathode performance decreases with current density and becomes negligible at high current density. Current density is found to influence fuel efficiency and methanol crossover significantly from the measurement of fuel efficiency at different current density. At high current density, high fuel efficiency can be achieved even at high temperature, indicating decreased methanol crossover.

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

    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.

  16. Direct effect of curcumin on porcine ovarian cell functions.

    Kádasi, Attila; Maruniaková, Nora; Štochmaľová, Aneta; Bauer, Miroslav; Grossmann, Roland; Harrath, Abdel Halim; Kolesárová, Adriana; Sirotkin, Alexander V

    2017-07-01

    Curcuma longa Linn (L.) is a plant widely used in cooking (in curry powder a.o.) and in folk medicine, but its action on reproductive processes and its possible mechanisms of action remain to be investigated. The objective of this study was to examine the direct effects of curcumin, the major Curcuma longa L. molecule, on basic ovarian cell functions such as proliferation, apoptosis, viability and steroidogenesis. Porcine ovarian granulosa cells were cultured with and without curcumin (at doses of 0, 1, 10 and 100μg/ml of medium). Markers of proliferation (accumulation of PCNA) and apoptosis (accumulation of bax) were analyzed by immunocytochemistry. The expression of mRNA for PCNA and bax was detected by RT-PCR. Cell viability was detected by trypan blue exclusion test. Release of steroid hormones (progesterone and testosterone) was measured by enzyme immunoassay (EIA). It was observed that addition of curcumin reduced ovarian cell proliferation (expression of both PCNA and its mRNA), promoted apoptosis (accumulation of both bax and its mRNA), reduced cell viability, and stimulated both progesterone and testosterone release. These observations demonstrate the direct suppressive effect of Curcuma longa L./curcumin on female gonads via multiple mechanisms of action - suppression of ovarian cell proliferation and viability, promotion of their apoptosis (at the level of mRNA transcription and subsequent accumulation of promoters of genes regulating these activities) and release of anti-proliferative and pro-apoptotic progesterone and androgen. The potential anti-gonadal action of curcumin should be taken into account by consumers of Curcuma longa L.-containing products. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    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.

    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 seps...

  18. Direct and dynamic detection of HIV-1 in living cells.

    Jonas Helma

    Full Text Available In basic and applied HIV research, reliable detection of viral components is crucial to monitor progression of infection. While it is routine to detect structural viral proteins in vitro for diagnostic purposes, it previously remained impossible to directly and dynamically visualize HIV in living cells without genetic modification of the virus. Here, we describe a novel fluorescent biosensor to dynamically trace HIV-1 morphogenesis in living cells. We generated a camelid single domain antibody that specifically binds the HIV-1 capsid protein (CA at subnanomolar affinity and fused it to fluorescent proteins. The resulting fluorescent chromobody specifically recognizes the CA-harbouring HIV-1 Gag precursor protein in living cells and is applicable in various advanced light microscopy systems. Confocal live cell microscopy and super-resolution microscopy allowed detection and dynamic tracing of individual virion assemblies at the plasma membrane. The analysis of subcellular binding kinetics showed cytoplasmic antigen recognition and incorporation into virion assembly sites. Finally, we demonstrate the use of this new reporter in automated image analysis, providing a robust tool for cell-based HIV research.

  19. Deterministic direct reprogramming of somatic cells to pluripotency.

    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.

  20. Evidence of direct and indirect rebound effect in households in EU-27 countries

    Freire-González, Jaume

    2017-01-01

    This research estimates the direct and indirect rebound effect of energy efficiency in households for the EU-27 countries (the first twenty-seven Member States of the European Union). A hybrid methodology that combines econometric estimates, environmental extended input-output analysis and re-spending models has been developed. Although most of the economies present values below 100%, there are seven countries situated above this critical threshold. By weighting individual estimates by GDP, an average value for the overall EU-27 economy has been found between 73.62% and 81.16%. These results suggest that the energy policy at the European level should be rethought if efficiency measures pursue reducing energy consumption and tackling climate change. - Highlights: • Empirical evidence of direct and indirect rebound effect is provided for EU-27. • Most economies have a rebound effect below the threshold of 100% (20 of them). • Additional energy efficiency measures are needed even with low direct rebounds.

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

    Marçal, L. A. B.; Magalhães-Paniago, R.; Malachias, Angelo, E-mail: angeloms@fisica.ufmg.br [Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, CEP 31270-901, Belo Horizonte (Brazil); Richard, M.-I. [European Synchrotron (ESRF), ID01 beamline, CS 40220, 38043 Grenoble Cedex 9 (France); Aix-Marseille University, IM2NP-CNRS, Faculté des Sciences de St Jérôme, 13397 Marseille (France); Cavallo, F. [Center for High Technology Materials, University of New Mexico, 1313 Goddard St., Albuquerque, New Mexico 87106 (United States); University of Wisconsin-Madison, 1500 Engineering Drive, Madison, Wisconsin 53706 (United States); Lagally, M. G. [University of Wisconsin-Madison, 1500 Engineering Drive, Madison, Wisconsin 53706 (United States); Schmidt, O. G. [Institute for Integrative Nanosciences, IFW-Dresden, D-01171 Dresden (Germany); Schülli, T. Ü. [European Synchrotron (ESRF), ID01 beamline, CS 40220, 38043 Grenoble Cedex 9 (France); Deneke, Ch. [Laboratório Nacional de Nanotecnologia (LNNano/CNPEM), C.P. 6192, CEP 13083-970, Campinas (Brazil)

    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.

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

    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. Copyright © 2011. Published by Elsevier Ltd.

  3. A novel membrane-less direct alcohol fuel cell

    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.

  4. Searching for evidence of a preferred rupture direction in small earthquakes at Parkfield

    Kane, D. L.; Shearer, P. M.; Allmann, B.; Vernon, F. L.

    2009-12-01

    Theoretical modeling of strike-slip ruptures along a bimaterial interface suggests that the interface will have a preferred rupture direction and will produce asymmetric ground motion (Shi and Ben-Zion, 2006). This could have widespread implications for earthquake source physics and for hazard analysis on mature faults because larger ground motions would be expected in the direction of rupture propagation. Studies have shown that many large global earthquakes exhibit unilateral rupture, but a consistently preferred rupture direction along faults has not been observed. Some researchers have argued that the bimaterial interface model does not apply to natural faults, noting that the rupture of the M 6 2004 Parkfield earthquake propagated in the opposite direction from previous M 6 earthquakes along that section of the San Andreas Fault (Harris and Day, 2005). We analyze earthquake spectra from the Parkfield area to look for evidence of consistent rupture directivity along the San Andreas Fault. We separate the earthquakes into spatially defined clusters and quantify the differences in high-frequency energy among earthquakes recorded at each station. Propagation path effects are minimized in this analysis because we compare earthquakes located within a small volume and recorded by the same stations. By considering a number of potential end-member models, we seek to determine if a preferred rupture direction is present among small earthquakes at Parkfield.

  5. Spatially patterned matrix elasticity directs stem cell fate

    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.

  6. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  7. Rapid, Directed Differentiation of Retinal Pigment Epithelial Cells from Human Embryonic or Induced Pluripotent Stem Cells

    Foltz, LP; Clegg, DO

    2017-01-01

    We describe a robust method to direct the differentiation of pluripotent stem cells into retinal pigment epithelial cells (RPE). The purpose of providing a detailed and thorough protocol is to clearly demonstrate each step and to make this readily available to researchers in the field. This protocol results in a homogenous layer of RPE with minimal or no manual dissection needed. The method presented here has been shown to be effective for induced pluripotent stem cells (iPSC) and human embry...

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

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

    2015-01-01

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

    Premnath, Priyatha, E-mail: priyatha.premnath@ryerson.ca [Micro/Nanofabrication Laboratory, Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada); Tavangar, Amirhossein, E-mail: atavanga@ryerson.ca [Micro/Nanofabrication Laboratory, Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada); Tan, Bo, E-mail: tanbo@ryerson.ca [Nanocharacterization Laboratory, Department of Aerospace Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada); Venkatakrishnan, Krishnan, E-mail: venkat@ryerson.ca [Micro/Nanofabrication Laboratory, Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, Canada M5B 2K3 (Canada)

    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

  10. Update on status of direct methanol fuel cells

    Reeve, R.W.

    2002-07-01

    This report reviews the progress in direct methanol fuel cell (DMFC) technology since 1995 and examines the opportunities for this technology in various market sectors. The report is divided into two parts. Part A describes the state-of-the-art of DMFC technology, developments in electrocatalysis relevant to DMFCs, single cell and stack performance, and polymer electrolyte membranes. Part B discusses the viability of current DMFCs for portable and automotive applications, and examines some niche markets, eg for remote power applications. Market opportunities, technical issues, applications and competing technologies are summarised. The report draws attention to the outstanding technical issues and recommends further development in a number of areas (eg inexpensive membranes with lower rates of methanol crossover, membranes with lower rates of water permeation, improved power density and methods to ensure solutions do not freeze in cold climates).

  11. Progress toward cell-directed therapy for phenylketonuria

    Harding, CO

    2009-01-01

    Phenylketonuria (PKU) is one of the most common inborn errors of metabolism with an annual incidence of approximately 1:16,000 live births in North America. Contemporary therapy relies upon lifelong dietary protein restriction and supplementation with phenylalanine-free medical foods. This therapy is expensive and unpalatable; dietary compliance is difficult to maintain throughout life. Non-adherence to the diet is associated with learning disabilities, adult-onset neurodegenerative disease, and maternal PKU syndrome. The fervent dream of many individuals with PKU is a more permanent cure for this disease. This paper will review ongoing efforts to develop viable cell-directed therapies, in particular cell transplantation and gene therapy, for the treatment of PKU. PMID:18498375

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

    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.

  13. Direct ethanol fuel cells with catalysed metal mesh anodes

    Chetty, Raghuram; Scott, Keith

    2007-01-01

    Platinum based binary and ternary catalysts prepared by thermal decomposition on titanium mesh were characterised and compared in terms of the electrochemical activity for ethanol oxidation. An enhancement in the catalytic activity was observed for the binary catalyst containing tin and ruthenium in their compositions with platinum. The catalysts were tested in single direct ethanol fuel cells and the result obtained with PtRu and PtSn showed that the mesh based electrodes show competitive performance in comparison to the conventional carbon based anodes

  14. Novel Materials for High Efficiency Direct Methanol Fuel Cells

    Carson, Stephen [Arkema Inc.; Mountz, David [Arkema Inc.; He, Wensheng [Arkema Inc.; Zhang, Tao [Arkema Inc.

    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.

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

    Zhongyuan Ren

    Full Text Available 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.

  16. Principles and Materials Aspects of Direct Alkaline Alcohol Fuel Cells

    Eileen Hao Yu

    2010-08-01

    Full Text Available Direct alkaline alcohol fuel cells (DAAFCs have attracted increasing interest over the past decade because of their favourable reaction kinetics in alkaline media, higher energy densities achievable and the easy handling of the liquid fuels. In this review, principles and mechanisms of DAAFCs in alcohol oxidation and oxygen reduction are discussed. Despite the high energy densities available during the oxidation of polycarbon alcohols they are difficult to oxidise. Apart from methanol, the complete oxidation of other polycarbon alcohols to CO2 has not been achieved with current catalysts. Different types of catalysts, from conventional precious metal catalyst of Pt and Pt alloys to other lower cost Pd, Au and Ag metal catalysts are compared. Non precious metal catalysts, and lanthanum, strontium oxides and perovskite-type oxides are also discussed. Membranes like the ones used as polymer electrolytes and developed for DAAFCs are reviewed. Unlike conventional proton exchange membrane fuel cells, anion exchange membranes are used in present DAAFCs. Fuel cell performance with DAAFCs using different alcohols, catalysts and membranes, as well as operating parameters are summarised. In order to improve the power output of the DAAFCs, further developments in catalysts, membrane materials and fuel cell systems are essential.

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

    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.

  18. Inward foreign direct investment and industrial restructuring: micro evidence – the Slovenian firms’ growth model

    Katja Zajc Kejžar

    2006-12-01

    Full Text Available We examine the impact of inward foreign direct investment (FDI on the growth of local firms in terms of employment and total factor productivity (TFP for the Slovenian manufacturing sector in the 1994-2003 period. The theoretically predicted channels through which inward FDI affects the firm dynamics in a host country prove to be in general significant. First, there is evidence of the direct impact offoreign firms through so-called direct technology transfer as foreign-owned firms have higher growth of TFP compared to domestically-owned firms after controlling for other determinants. Secondly, the entry of foreign firms stimulates the reshuffling of the resources from less to more efficient local firms. The firm selection process is, namely, characterised by the least efficient firms experiencing a drop in their employment growth upon a foreign firm’s entry. Thirdly, regarding the productivity spillover effects from foreign to local firms we provide indirect evidence that they mostly operate through vertical linkages rather than within the same industry.In general, it seems that not all firms are equally able to benefit from foreign firms’ presence and that absorptive capacity plays an important role.

  19. Direct analysis in real time mass spectrometry for analysis of sexual assault evidence.

    Musah, Rabi A; Cody, Robert B; Dane, A John; Vuong, Angela L; Shepard, Jason R E

    2012-05-15

    Sexual assault crimes are vastly underreported and suffer from alarmingly low prosecution and conviction rates. The key scientific method to aid in prosecution of such cases is forensic DNA analysis, where biological evidence such as semen collected using a rape test kit is used to determine a suspect's DNA profile. However, the growing awareness by criminals of the importance of DNA in the prosecution of sexual assaults has resulted in increased condom use by assailants as a means to avoid leaving behind their DNA. Thus, other types of trace evidence are important to help corroborate victims' accounts, exonerate the innocent, link suspects to the crime, or confirm penetration. Direct Analysis in Real Time Mass Spectrometry (DART-MS) was employed for the comprehensive characterization of non-DNA trace evidence associated with sexual assault. The ambient ionization method associated with DART-MS is extremely rapid and samples are processed instantaneously, without the need for extraction, sample preparation, or other means that might compromise forensic evidence for future analyses. In a single assay, we demonstrated the ability to identify lubricant formulations associated with sexual assault, such as the spermicide nonoxynol-9, compounds used in condom manufacture, and numerous other trace components as probative evidence. In addition, the method can also serve to identify compounds within trace biological residues, such as fatty acids commonly identified in latent fingerprints. Characterization of lubricant residues as probative evidence serves to establish a connection between the victim and the perpetrator, and the availability of these details may lead to higher rates of prosecution and conviction, as well as more severe penalties. The methodology described here opens the way for the adoption of a comprehensive, rapid, and sensitive analysis for use in crime labs, while providing knowledge that can inform and guide criminal justice policy and practice

  20. Pt based anode catalysts for direct ethanol fuel cells

    Zhou, Weijiang; Zhou, Zhenhua; Song, Shuqin; Li, Wenzhen; Sun, Gongquan; Xin, Qin [Direct Alcohol Fuel Cell Laboratory, Dalian Institute of Chemical Physics, CAS, P.O. Box 110, Dalian 116023 (China); Tsiakaras, Panagiotis [Department of Mechanical and Industrial Engineering, University of Thessalia, Pedion Areos, GR 38334 Volos (Greece) 7

    2003-11-10

    In the present work several Pt-based anode catalysts supported on carbon XC-72R were prepared with a novel method and characterized by means of XRD, TEM and XPS analysis. It was found that all these catalysts are consisted of uniform nanosized particles with sharp distribution and Pt lattice parameter decreases with the addition of Ru or Pd and increases with the addition of Sn or W. Cyclic voltammetry (CV) measurements and single direct ethanol fuel cell (DEFC) tests jointly showed that the presence of Sn, Ru and W enhances the activity of Pt towards ethanol electro-oxidation in the following order: Pt{sub 1}Sn{sub 1}/C>Pt{sub 1}Ru{sub 1}/C>Pt{sub 1}W{sub 1}/C>Pt{sub 1}Pd{sub 1}/C>Pt/C. Moreover, Pt{sub 1}Ru{sub 1}/C further modified by W and Mo showed improved ethanol electro-oxidation activity, but its DEFC performance was found to be inferior to that measured for Pt{sub 1}Sn{sub 1}/C. Under this respect, several PtSn/C catalysts with different Pt/Sn atomic ratio were also identically prepared and characterized and their direct ethanol fuel cell performances were evaluated. It was found that the single direct ethanol fuel cell having Pt{sub 1}Sn{sub 1}/C or Pt{sub 3}Sn{sub 2}/C or Pt{sub 2}Sn{sub 1}/C as anode catalyst showed better performances than those with Pt{sub 3}Sn{sub 1}/C or Pt{sub 4}Sn{sub 1}/C. It was also found that the latter two cells exhibited higher performances than the single cell using Pt{sub 1}Ru{sub 1}/C, which is exclusively used in PEMFC as anode catalyst for both methanol electro-oxidation and CO-tolerance. This distinct difference in DEFC performance between the catalysts examined here would be attributed to the so-called bifunctional mechanism and to the electronic interaction between Pt and additives. It is thought that an amount of -OH{sub ads}, an amount of surface Pt active sites and the conductivity effect of PtSn/C catalysts would determine the activity of PtSn/C with different Pt/Sn ratios. At lower temperature values or at low

  1. Improved Anode for a Direct Methanol Fuel Cell

    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

  2. Direct Carbon Fuel Cell System Utilizing Solid Carbonaceous Fuels

    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

  3. Directive Nanophysical Cues for Regenerative Neural Cell Systems

    Ayres, Virginia; Tiryaki, Volkan Mujdat; Ahmed, Ijaz; Shreiber, David

    Until recently, implantables such as stents, probes, wafers and scaffolds have been viewed as passive vehicles for the delivery of physical, pharmacological and cellular interventions. Recent research, however, indicates that the physical environments that implantables present supply directive cues in their own right that work in conjunction with biochemical cues and produce a jointly-directed outcome. We will present our research in CNS repairs using advanced scanning probe microscopy, electron microscopies and contact angle measurements to quantitatively describe the nanoscale elasticity, surface roughness, work of adhesion and surface polarity for investigation of scaffold environments. We will also present our research using super-resolution immunocytochemistry and atomic force microscopy to evaluate neural cell morphological responses with associated micro filament, microtubule and intermediate filament expressions, along with results on how and which integrin-family receptors are possibly involved. Finally, we will present our novel application of k-means cluster analysis applied across multiple experimental modalities for quantification of synergistic scaffold properties and cell responses.

  4. A gradient activation method for direct methanol fuel cells

    Liu, Guicheng; Yang, Zhaoyi; Halim, Martin; Li, Xinyang; Wang, Manxiang; Kim, Ji Young; Mei, Qiwen; Wang, Xindong; Lee, Joong Kee

    2017-01-01

    Highlights: • A gradient activation method was reported firstly for direct methanol fuel cells. • The activity recovery of Pt-based catalyst was introduced into the novel activation process. • The new activation method led to prominent enhancement of DMFC performance. • DMFC performance was improved with the novel activation step by step within 7.5 h. - Abstract: To realize gradient activation effect and recover catalytic activity of catalyst in a short time, a gradient activation method has firstly been proposed for enhancing discharge performance and perfecting activation mechanism of the direct methanol fuel cell (DMFC). This method includes four steps, i.e. proton activation, activity recovery activation, H_2-O_2 mode activation and forced discharging activation. The results prove that the proposed method has gradually realized replenishment of water and protons, recovery of catalytic activity of catalyst, establishment of transfer channels for electrons, protons, and oxygen, and optimization of anode catalyst layer for methanol transfer in turn. Along with the novel activation process going on, the DMFC discharge performance has been improved, step by step, to more than 1.9 times higher than that of the original one within 7.5 h. This method provides a practicable activation way for the real application of single DMFCs and stacks.

  5. Contingency management: New directions and remaining challenges for an evidence-based intervention

    Rash, Carla J.; Stitzer, Maxine; Weinstock, Jeremiah

    2016-01-01

    This article introduces the special issue on contingency management (CM), an efficacious intervention for the treatment of substance use disorders with low uptake in clinical settings that is not commensurate with evidence for efficacy. In this special issue of the Journal of Substance Abuse Treatment, we present 16 articles representing the latest research in efficacy, implementation, and technological advances related to CM. Combined, this collection of articles highlights the diverse populations, settings, and applications of CM in the treatment of substance use disorders. We conclude by highlighting directions for future research, particularly those that may increase CM’s appeal and uptake in routine clinical care. PMID:27746057

  6. Sleep Deprivation Promotes Habitual Control over Goal-Directed Control: Behavioral and Neuroimaging Evidence.

    Chen, Jie; Liang, Jie; Lin, Xiao; Zhang, Yang; Zhang, Yan; Lu, Lin; Shi, Jie

    2017-12-06

    Sleep is one of the most fundamental processes of life, playing an important role in the regulation of brain function. The long-term lack of sleep can cause memory impairments, declines in learning ability, and executive dysfunction. In the present study, we evaluated the effects of sleep deprivation on instrumental learning behavior, particularly goal-directed and habitual actions in humans, and investigated the underlying neural mechanisms. Healthy college students of either gender were enrolled and randomly divided into sleep deprivation group and sleep control group. fMRI data were collected. We found that one night of sleep deprivation led to greater responsiveness to stimuli that were associated with devalued outcomes in the slips-of-action test, indicating a deficit in the formation of goal-directed control and an overreliance on habits. Furthermore, sleep deprivation had no effect on the expression of acquired goal-directed action. The level of goal-directed action after sleep deprivation was positively correlated with baseline working memory capacity. The neuroimaging data indicated that goal-directed learning mainly recruited the ventromedial PFC (vmPFC), the activation of which was less pronounced during goal-directed learning after sleep deprivation. Activation of the vmPFC during goal-directed learning during training was positively correlated with the level of goal-directed action performance. The present study suggests that people rely predominantly on habits at the expense of goal-directed control after sleep deprivation, and this process involves the vmPFC. These results contribute to a better understanding of the effects of sleep loss on decision-making. SIGNIFICANCE STATEMENT Understanding the cognitive consequences of sleep deprivation has become extremely important over the past half century, given the continued decline in sleep duration in industrialized societies. Our results provide novel evidence that goal-directed action may be

  7. Foreign direct investment and policy framework: New Granger causality evidence from African countries

    Rafiu Adewale Aregbeshola

    2014-11-01

    Full Text Available The strategic importance of foreign direct investment in the contemporary economies has been tremendous.While various countries (developed and developing economies have benefitted from the direct and spillovereffects of FDI, which range from improved technology and knowledge diffusion through to individual andcorporate capability enhancement, FDI outflow remains largely channelled to the developed countries, andthe rapidly developing countries in Asia and South America. Evidence suggests that the developmentenhancingeffects of FDI are felt more highly in the developing economies, such as economies in Africa.However, FDI inflow to the developing economies has been very low. Using data generated from the AfricanDevelopment Indicators (ADI between 1980 and 2008 in econometric estimations, this paper finds thatgovernment policies (especially fiscal and monetary policies play significant roles in facilitating FDI inflow tothe African countries studied. The study thereby suggests an improved regulatory framework to make Africamore attractive to inflow of FDI.

  8. Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation

    K Murai

    2010-01-01

    Full Text Available Although intervertebral disc herniation and associated sciatica is a common disease, its molecular pathogenesis is not well understood. Immune responses are thought to be involved. This study provides direct evidence that even non-degenerated nucleus pulposus (NP cells elicit immune responses. An in vitro colony forming inhibition assay demonstrated the suppressive effects of autologous spleen cells on NP cells and an in vitro cytotoxicity assay showed the positive cytotoxic effects of natural killer (NK cells and macrophages on NP cells. Non-degenerated rat NP tissues transplanted into wild type rats and immune-deficient mice demonstrated a significantly higher NP cell survival rate in immune-deficient mice. Immunohistochemical staining showed the presence of macrophages and NK cells in the transplanted NP tissues. These results suggest that even non-degenerated autologous NP cells are recognized by macrophages and NK cells, which may have an immunological function in the early phase of disc herniation. These findings contribute to understanding resorption and the inflammatory reaction to disc herniation.

  9. Emerging Evidence for Platelets as Immune and Inflammatory Effector Cells

    Matthew Thomas Rondina

    2014-12-01

    Full Text Available While traditionally recognized for their roles in hemostatic pathways, emerging evidence demonstrates that platelets have previously unrecognized, dynamic roles that span the immune continuum. These newly-recognized platelet functions, including the secretion of immune mediators, interactions with endothelial cells, monocytes, and neutrophils, toll-like receptor (TLR mediated responses, and induction of neutrophil extracellular trap (NET formation, bridge thrombotic and inflammatory pathways and contribute to host defense mechanisms against invading pathogens. In this focused review, we highlight several of these emerging aspects of platelet biology and their implications in clinical infectious syndromes.

  10. A microfluidic direct formate fuel cell on paper.

    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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Passive direct methanol fuel cells for portable electronic devices

    Achmad, F.; Kamarudin, S.K.; Daud, W.R.W.; Majlan, E.H.

    2011-01-01

    Due to the increasing demand for electricity, clean, renewable energy resources must be developed. Thus, the objective of the present study was to develop a passive direct methanol fuel cell (DMFC) for portable electronic devices. The power output of six dual DMFCs connected in series with an active area of 4 cm 2 was approximately 600 mW, and the power density of the DMFCs was 25 mW cm -2 . The DMFCs were evaluated as a power source for mobile phone chargers and media players. The results indicated that the open circuit voltage of the DMFC was between 6.0 V and 6.5 V, and the voltage under operating conditions was 4.0 V. The fuel cell was tested on a variety of cell phone chargers, media players and PDAs. The cost of energy consumption by the proposed DMFC was estimated to be USD 20 W -1 , and the cost of methanol is USD 4 kW h. Alternatively, the local conventional electricity tariff is USD 2 kW h. However, for the large-scale production of electronic devices, the cost of methanol will be significantly lower. Moreover, the electricity tariff is expected to increase due to the constraints of fossil fuel resources and pollution. As a result, DMFCs will become competitive with conventional power sources.

  12. Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate.

    Fan, Yi; Hanai, Jun-Ichi; Le, Phuong T; Bi, Ruiye; Maridas, David; DeMambro, Victoria; Figueroa, Carolina A; Kir, Serkan; Zhou, Xuedong; Mannstadt, Michael; Baron, Roland; Bronson, Roderick T; Horowitz, Mark C; Wu, Joy Y; Bilezikian, John P; Dempster, David W; Rosen, Clifford J; Lanske, Beate

    2017-03-07

    Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1 + RANKL + marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Study of Galfenol direct cytotoxicity and remote microactuation in cells.

    Vargas-Estevez, Carolina; Blanquer, Andreu; Dulal, Prabesh; Pérez Del Real, Rafael; Duch, Marta; Ibáñez, Elena; Barrios, Leonardo; Murillo, Gonzalo; Torras, Núria; Nogués, Carme; Stadler, Bethanie J H; Plaza, José A; Esteve, Jaume

    2017-09-01

    Remote microactuators are of great interest in biology and medicine as minimally-invasive tools for cellular stimulation. Remote actuation can be achieved by active magnetostrictive transducers which are capable of changing shape in response to external magnetic fields thereby creating controlled displacements. Among the magnetostrictive materials, Galfenol, the multifaceted iron-based smart material, offers high magnetostriction with robust mechanical properties. In order to explore these capabilities for biomedical applications, it is necessary to study the feasibility of material miniaturization in standard fabrication processes as well as evaluate the biocompatibility. Here we develop a technology to fabricate, release, and suspend Galfenol-based microparticles, without affecting the integrity of the material. The morphology, composition and magnetic properties of the material itself are characterized. The direct cytotoxicity of Galfenol is evaluated in vitro using human macrophages, osteoblast and osteosarcoma cells. In addition, cytotoxicity and actuation of Galfenol microparticles in suspension are evaluated using human macrophages. The biological parameters analyzed indicate that Galfenol is not cytotoxic, even after internalization of some of the particles by macrophages. The microparticles were remotely actuated forming intra- and extracellular chains that did not impact the integrity of the cells. The results propose Galfenol as a suitable material to develop remote microactuators for cell biology studies and intracellular applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

    Romuald Polczyk

    2016-05-01

    Full Text Available Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence for the existence of the two factors has been scarce. In the present study, more sophisticated and reliable tools for measuring suggestibility were applied than in the previous research, in the hope that better measurement would reveal the factor structure of suggestibility. Two tests of direct suggestibility were used: the Harvard Group Scale of Hypnotic Susceptibility, Form A, measuring hypnotic susceptibility, and the Barber Suggestibility Scale, measuring non-hypnotic direct imaginative suggestibility. Three tests served to measure indirect suggestibility: the Sensory Suggestibility Scale, measuring indirect suggestibility relating to perception; the Gudjonsson Suggestibility Scale, measuring the tendency to yield to suggestive questions and changing answers after negative feedback; and the Emotional Dialogs Tests, measuring the tendency to perceive nonexistent aggression. Participants and procedure In sum, 115 participants were tested, 69 women, 49 men, mean age 22.20 years, SD = 2.20. Participants were tested in two sessions, lasting for a total of four hours. Results Confirmatory factor analyses confirmed the existence of two uncorrelated factors of suggestibility: direct and indirect. Conclusions Suggestibility may indeed involve two factors, direct and indirect, and failure to discover them in previous research may be due to methodological problems.

  15. Direct measurement of helical cell motion of the spirochete leptospira.

    Nakamura, Shuichi; Leshansky, Alexander; Magariyama, Yukio; Namba, Keiichi; Kudo, Seishi

    2014-01-07

    Leptospira are spirochete bacteria distinguished by a short-pitch coiled body and intracellular flagella. Leptospira cells swim in liquid with an asymmetric morphology of the cell body; the anterior end has a long-pitch spiral shape (S-end) and the posterior end is hook-shaped (H-end). Although the S-end and the coiled cell body called the protoplasmic cylinder are thought to be responsible for propulsion together, most observations on the motion mechanism have remained qualitative. In this study, we analyzed the swimming speed and rotation rate of the S-end, protoplasmic cylinder, and H-end of individual Leptospira cells by one-sided dark-field microscopy. At various viscosities of media containing different concentrations of Ficoll, the rotation rate of the S-end and protoplasmic cylinder showed a clear correlation with the swimming speed, suggesting that these two helical parts play a central role in the motion of Leptospira. In contrast, the H-end rotation rate was unstable and showed much less correlation with the swimming speed. Forces produced by the rotation of the S-end and protoplasmic cylinder showed that these two helical parts contribute to propulsion at nearly equal magnitude. Torque generated by each part, also obtained from experimental motion parameters, indicated that the flagellar motor can generate torque >4000 pN nm, twice as large as that of Escherichia coli. Furthermore, the S-end torque was found to show a markedly larger fluctuation than the protoplasmic cylinder torque, suggesting that the unstable H-end rotation might be mechanically related to changes in the S-end rotation rate for torque balance of the entire cell. Variations in torque at the anterior and posterior ends of the Leptospira cell body could be transmitted from one end to the other through the cell body to coordinate the morphological transformations of the two ends for a rapid change in the swimming direction. Copyright © 2014 Biophysical Society. Published by Elsevier Inc

  16. Direct imaging of APP proteolysis in living cells.

    Parenti, Niccoló; Del Grosso, Ambra; Antoni, Claudia; Cecchini, Marco; Corradetti, Renato; Pavone, Francesco S; Calamai, Martino

    2017-01-01

    Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of A β peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. A β peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue. Kits available commercially measure the enzymatic activity of the secretases from cells lysates, in vitro . By contrast, we have developed a prototypal rapid bioassay that provides visible information on the proteolytic processing of APP directly in living cells. APP was fused to a monomeric variant of the green fluorescent protein and a monomeric variant of the red fluorescent protein at the C-terminal and N-terminal (mChAPPmGFP), respectively. Changes in the proteolytic processing rate in transfected human neuroblastoma and rat neuronal cells were imaged with confocal microscopy as changes in the red/green fluorescence intensity ratio. The significant decrease in the mean red/green ratio observed in cells over-expressing the β -secretase BACE1, or the α -secretase ADAM10, fused to a monomeric blue fluorescent protein confirms that the proteolytic site is still accessible. Specific siRNA was used to evaluate the contribution of endogenous BACE1. Interestingly, we found that the degree of proteolytic processing of APP is not completely homogeneous within the same single cell, and that there is a high degree of variability between cells of the same type. We were also able to follow with a fluorescence spectrometer the changes in the red emission intensity of the extracellular medium when BACE1 was overexpressed. This represents a complementary approach to fluorescence microscopy for rapidly detecting changes in the proteolytic processing

  17. Evaluating the evidence: direct-to-consumer screening tests advertised online.

    Lovett, Kimberly M; Mackey, Timothy K; Liang, Bryan A

    2012-09-01

    Unsupervised online direct-to-consumer (DTC) access to medical services has rapidly expanded to medical screening tests, which have not been critically evaluated for their evidence basis. The objective of this study is to identify the scope of online-advertised DTC screening tests, outline the evidence for use of available DTC testing and suggest regulatory reform to address the relevant issues. An observational study of website advertisements, testing services and counselling/follow-up services for DTC testing was conducted. Data were collected from websites between 4 April and 1 June 2011. Each website was assessed for tests offered, advertised indications and availability of counselling/follow-up services. Advertised testing indications were compared with US Preventive Services Task Force recommendations and/or specialty guidelines and categorized as Supported, Against, Insufficient Evidence or No Guidance. Of 20 companies identified as offering DTC screening tests, 95% (19/20) do not clearly offer pretest counselling, post-test counselling and/or test follow-up. One hundred and twenty-seven different tests were identified. Only 19/127 (15%) could be Supported for screening in a target group selected for testing; 38/127 (30%) were given recommendations to avoid use in specific target group(s) selected for testing ('Against recommendations'); 29/127 (23%) had Insufficient Evidence of value, and for 64/127 (50%) No Guidance could be given. Only 4/127 (3%) tests were Supported for general screening use. Virtually all identified medical tests advertised and offered DTC are not recommended for use in screening by evidence-based guidelines. Limited oversight may lead to inaccurate self-diagnosis, treatment and wasted health resources.

  18. Direct Differentiation of Human Pluripotent Stem Cells into Haploid Spermatogenic Cells

    Charles A. Easley, IV

    2012-09-01

    Full Text Available Human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been shown to differentiate into primordial germ cells (PGCs but not into spermatogonia, haploid spermatocytes, or spermatids. Here, we show that hESCs and hiPSCs differentiate directly into advanced male germ cell lineages, including postmeiotic, spermatid-like cells, in vitro without genetic manipulation. Furthermore, our procedure mirrors spermatogenesis in vivo by differentiating PSCs 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 that are uniquely found in spermatids and/or sperm. These spermatids show uniparental genomic imprints similar to those of human sperm on two loci: H19 and IGF2. These results demonstrate that male PSCs have the ability to differentiate directly into advanced germ cell lineages and may represent a novel strategy for studying spermatogenesis in vitro.

  19. Spermatogonial stem cell transplantation and male infertility: Current status and future directions

    Connor M. Forbes

    2018-03-01

    Full Text Available Objective: To summarise the current state of research into spermatogonial stem cell (SSC therapies with a focus on future directions, as SSCs show promise as a source for preserving or initiating fertility in otherwise infertile men. Materials and methods: We performed a search for publications addressing spermatogonial stem cell transplantation in the treatment of male infertility. The search engines PubMed and Google Scholar were used from 1990 to 2017. Search terms were relevant for spermatogonial stem cell therapies. Titles of publications were screened for relevance; abstracts were read, if related and full papers were reviewed for directly pertinent original research. Results: In all, 58 papers were found to be relevant to this review, and were included in appropriate subheadings. This review discusses the various techniques that SSCs are being investigated to treat forms of male infertility. Conclusions: Evidence does not yet support clinical application of SSCs in humans. However, significant progress in the in vitro and in vivo development of SSCs, including differentiation into functional germ cells, gives reason for cautious optimism for future research. Keywords: Non-obstructive azoospermia, Fertility preservation, Onco-fertility, Male infertility, Stem cell therapy, Allograft

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

    Bowes, Timothy; Gupta, Radhey S.

    2008-01-01

    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

  1. B-1 cell immunoglobulin directed against oxidation-specific epitopes

    Dimitrios eTsiantoulas

    2013-01-01

    Full Text Available Natural antibodies (NAbs are pre-existing antibodies with germline origin that arise in the absence of previous exposure to foreign antigens. NAbs are produced by B-1 lymphocytes and are primarily of the IgM isotype. There is accumulating evidence that - in addition to their role in antimicrobial host defense - NAbs exhibit important housekeeping functions by facilitating the non-immunogenic clearance of apoptotic cells as well as the removal of (neo-self antigens. These properties are largely mediated by the ability of NAbs to recognize highly conserved and endogenously generated structures, which are exemplified by so-called oxidation-specific epitopes (OSEs that are products of lipid peroxidation. The generation of OSEs as well as their interaction with the immune system have been studied extensively in the context of atherosclerosis, a chronic inflammatory disease of the vascular wall that is characterized by the accumulation of cellular debris and oxidized low-density lipoproteins (OxLDL. Both apoptotic cells as well as OxLDL carry OSEs that are targeted by NAbs. Therefore, OSEs represent stress-induced neo-self structures that mediate recognition of metabolic waste (e.g. cellular debris by NAbs, allowing its safe disposal, which has fundamental implications in health and disease.

  2. Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees.

    Catherine Hobaiter

    2014-09-01

    Full Text Available 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.

  3. Social network analysis shows direct evidence for social transmission of tool use in wild chimpanzees.

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

    2014-09-01

    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.

  4. A novel direct carbon fuel cell by approach of tubular solid oxide fuel cells

    Liu, Renzhu; Zhao, Chunhua; Li, Junliang; Zeng, Fanrong; Wang, Shaorong; Wen, Tinglian; Wen, Zhaoyin [CAS Key Laboratory of Materials for Energy Conversion, Shanghai Inorganic Energy Materials and Power Source Engineering Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences (SICCAS), 1295 Dingxi Road, Shanghai 200050 (China)

    2010-01-15

    A direct carbon fuel cell based on a conventional anode-supported tubular solid oxide fuel cell, which consisted of a NiO-YSZ anode support tube, a NiO-ScSZ anode functional layer, a ScSZ electrolyte film, and a LSM-ScSZ cathode, has been successfully achieved. It used the carbon black as fuel and oxygen as the oxidant, and a preliminary examination of the DCFC has been carried out. The cell generated an acceptable performance with the maximum power densities of 104, 75, and 47 mW cm{sup -2} at 850, 800, and 750 C, respectively. These results demonstrate the feasibility for carbon directly converting to electricity in tubular solid oxide fuel cells. (author)

  5. Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

    Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B.; Rubin, D.H.

    1988-01-01

    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 51 Cr, [ 14 C]choline, and [ 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

  6. Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

    Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B. (Stanford Univ. School of Medicine, CA (USA) Palo Alto Veterans Administration Medical Center, CA (USA)); Rubin, D.H. (Univ. of Pennsylvania, Philadelphia (USA))

    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.

  7. Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

    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.

  8. Membranes for direct ethanol fuel cells: An overview

    Zakaria, Z.; Kamarudin, S.K.; Timmiati, S.N.

    2016-01-01

    Highlights: • DEFCs have emerged as alternative energy source. • But many issue need to be addressed. • This paper describes current problem and advancement of membrane in DEFC. - Abstract: Direct ethanol fuel cells (DEFCs) are attractive as a power source options because ethanol is a nontoxic, leading to ease of handling and a high energy density fuel, leading to high system energy density. However, to provide practical DEFCs power source there are several issues that still must be addressed including low power density, effect of ethanol crossover on efficiency of fuel utilization, electrical, mechanical and thermal stability and water uptake of the DEFCs electrolyte membrane. This paper describes the proton exchange membrane and alkaline exchange membrane for DEFCs, focusing on current problems and advancements in DEFC membranes. It also presents the specifications and performances of the membranes used in DEFC.

  9. Development of an electrode for direct methanol fuel cell

    Ramzia, A. M. S.; Iqbal, J.

    2006-01-01

    This paper presents the efficient use of platinum catalyst ruthenium with in the anode of a Direct Methanol Fuel Cell (DMFC). This is achieved by depositing platinum and ruthenium nano-particles on the pre-refluxed multi-walled carbon nano-tubes (MWCNT): MWCNTs were synthesized using the Chemical Vapor Deposition (CVD) with floating catalyst technique. The synthesized carbon nano tubes (CNT) were refluxed in 12M nitric acid to produce anchoring sites on the surface of the CNT. The platinum and ruthenium nano-particles were in a ratio of (3.1). These particles are deposited on the surface of the CNT at 60 wt % by reduction in ethylene glycol. Transmission micrograph (TEM) and scanning electron micrograph (SEM) images show the success of the deposition method. (author)

  10. Thin Film Catalyst Layers for Direct Methanol Fuel Cells

    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.

  11. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    Li, Wen-Zhong; Ai, Zhi-Ying [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Wang, Zhi-Wei [School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027 (China); Chen, Lin-Lin [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Guo, Ze-Kun, E-mail: gzknwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Zhang, Yong, E-mail: zylabnwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China)

    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.

  12. Relating Direct Methanol Fuel Cell Performance to Measurements in a Liquid Half Cell

    Pedersen, Christoffer Mølleskov; Tynelius, Oskar; Lund-Olesen, Torsten

    2015-01-01

    Direct methanol fuel cells (DMFC) could act as a replacement for batteries in low power electronics. For instance, micro—DMFC’s could be used to power hearing instruments[1]. The power output of a DMFC is limited by the sluggish kinetics of both the methanol oxidation reaction (MOR) on the anode ...... Cells Bull. 2012 (2012) 12–16. doi:10.1016/S1464-2859(12)70367-X....

  13. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

    Willett, Christopher G; Boucher, Yves; di Tomaso, Emmanuelle; Duda, Dan G; Munn, Lance L; Tong, Ricky T; Chung, Daniel C; Sahani, Dushyant V; Kalva, Sanjeeva P; Kozin, Sergey V; Mino, Mari; Cohen, Kenneth S; Scadden, David T; Hartford, Alan C; Fischman, Alan J; Clark, Jeffrey W; Ryan, David P; Zhu, Andrew X; Blaszkowsky, Lawrence S; Chen, Helen X; Shellito, Paul C; Lauwers, Gregory Y; Jain, Rakesh K

    2009-01-01

    The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors. PMID:14745444

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

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

    2014-07-07

    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. 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. 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. The total number of participants was 14 338. Health effects classified under the International Classification of Diseases (ICD-10). 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. 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. Policymakers should consider safety issues when working on relaxing EWTD for doctors. Published by the

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

    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

  16. Direct economic burden of hepatitis B virus related diseases: evidence from Shandong, China.

    Lu, Jingjing; Xu, Aiqiang; Wang, Jian; Zhang, Li; Song, Lizhi; Li, Renpeng; Zhang, Shunxiang; Zhuang, Guihua; Lu, Mingshan

    2013-01-31

    Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the economic burden associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the economic disease burden of HBV, we conducted a survey to investigate the direct economic burden of acute and chronic hepatitis B, cirrhosis and liver cancer caused by HBV-related disease. From April 2010 to November 2010, we conducted a survey of inpatients with HBV-related diseases and who were hospitalized for seven or more days in one of the seven tertiary and six secondary hospitals in Shandong, China. Patients were recorded consecutively within a three-to-five month time period from each sampled hospital; an in-person survey was conducted to collect demographic and socio-economic information, as well as direct medical and nonmedical expenses during the last month and last year prior to the current hospitalization. Direct medical costs included total outpatient, inpatient, and self-treatment expenditures; direct nonmedical costs included spending on nutritional supplements, transportation, and nursing. Direct medical costs during the current hospitalization were also obtained from the hospital financial database. The direct economic cost was calculated as the sum of direct medical and nonmedical costs. Our results call for the importance of implementing clinical guideline, improving system accountability, and helping secondary and smaller hospitals to improve efficiency. This has important policy implication for the on-going hospital reform in China. Our data based on inpatients with HBV-related diseases suggested that the direct cost in US dollars for acute hepatitis B, severe hepatitis B, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis and primary liver cancer was $2954, $10834, $4552, $7400.28, $6936 and $10635, respectively. These costs ranged from 30.72% (for acute

  17. Direct economic burden of hepatitis B virus related diseases: evidence from Shandong, China

    Lu Jingjing

    2013-01-01

    Full Text Available Abstract Background Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the economic burden associated with hepatitis B virus (HBV related diseases is not well addressed. In order to provide evidence to address the economic disease burden of HBV, we conducted a survey to investigate the direct economic burden of acute and chronic hepatitis B, cirrhosis and liver cancer caused by HBV-related disease. Methods From April 2010 to November 2010, we conducted a survey of inpatients with HBV-related diseases and who were hospitalized for seven or more days in one of the seven tertiary and six secondary hospitals in Shandong, China. Patients were recorded consecutively within a three-to-five month time period from each sampled hospital; an in-person survey was conducted to collect demographic and socio-economic information, as well as direct medical and nonmedical expenses during the last month and last year prior to the current hospitalization. Direct medical costs included total outpatient, inpatient, and self-treatment expenditures; direct nonmedical costs included spending on nutritional supplements, transportation, and nursing. Direct medical costs during the current hospitalization were also obtained from the hospital financial database. The direct economic cost was calculated as the sum of direct medical and nonmedical costs. Our results call for the importance of implementing clinical guideline, improving system accountability, and helping secondary and smaller hospitals to improve efficiency. This has important policy implication for the on-going hospital reform in China. Results Our data based on inpatients with HBV-related diseases suggested that the direct cost in US dollars for acute hepatitis B, severe hepatitis B, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis and primary liver cancer was $2954, $10834, $4552, $7400.28, $6936 and $10635

  18. Evidence for parallel consolidation of motion direction and orientation into visual short-term memory.

    Rideaux, Reuben; Apthorp, Deborah; Edwards, Mark

    2015-02-12

    Recent findings have indicated the capacity to consolidate multiple items into visual short-term memory in parallel varies as a function of the type of information. That is, while color can be consolidated in parallel, evidence suggests that orientation cannot. Here we investigated the capacity to consolidate multiple motion directions in parallel and reexamined this capacity using orientation. This was achieved by determining the shortest exposure duration necessary to consolidate a single item, then examining whether two items, presented simultaneously, could be consolidated in that time. The results show that parallel consolidation of direction and orientation information is possible, and that parallel consolidation of direction appears to be limited to two. Additionally, we demonstrate the importance of adequate separation between feature intervals used to define items when attempting to consolidate in parallel, suggesting that when multiple items are consolidated in parallel, as opposed to serially, the resolution of representations suffer. Finally, we used facilitation of spatial attention to show that the deterioration of item resolution occurs during parallel consolidation, as opposed to storage. © 2015 ARVO.

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

    Brandl, Simon J; Bellwood, David R

    2015-09-25

    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.

  20. Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A.

    Cadzow, Murray; Merriman, Tony R; Boocock, James; Dalbeth, Nicola; Stamp, Lisa K; Black, Michael A; Visscher, Peter M; Wilcox, Phillip L

    2016-11-15

    The gene PPARGC1A, in particular the Gly482Ser variant (rs8192678), had been proposed to be subject to natural selection, particularly in recent progenitors of extant Polynesian populations. Reasons include high levels of population differentiation and increased frequencies of the derived type 2 diabetes (T2D) risk 482Ser allele, and association with body mass index (BMI) in a small Tongan population. However, no direct statistical tests for selection have been applied. Using a range of Polynesian populations (Tongan, Māori, Samoan) we re-examined evidence for association between Gly482Ser with T2D and BMI as well as gout. Using also Asian, European, and African 1000 Genome Project samples a range of statistical tests for selection (F ST , integrated haplotype score (iHS), cross population extended haplotype homozygosity (XP-EHH), Tajima's D and Fay and Wu's H) were conducted on the PPARGC1A locus. No statistically significant evidence for association between Gly482Ser and any of BMI, T2D or gout was found. Population differentiation (F ST ) was smallest between Asian and Pacific populations (New Zealand Māori ≤ 0.35, Samoan ≤ 0.20). When compared to European (New Zealand Māori ≤ 0.40, Samoan ≤ 0.25) or African populations (New Zealand Māori ≤ 0.80, Samoan ≤ 0.66) this differentiation was larger. We did not find any strong evidence for departure from neutral evolution at this locus when applying any of the other statistical tests for selection. However, using the same analytical methods, we found evidence for selection in specific populations at previously identified loci, indicating that lack of selection was the most likely explanation for the lack of evidence of selection in PPARGC1A. We conclude that there is no compelling evidence for selection at this locus, and that this gene should not be considered a candidate thrifty gene locus in Pacific populations. High levels of population differentiation at this locus and the

  1. Recovery Act: Advanced Direct Methanol Fuel Cell for Mobile Computing

    Fletcher, James H. [University of North Florida; Cox, Philip [University of North Florida; Harrington, William J [University of North Florida; Campbell, Joseph L [University of North Florida

    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

  2. Improved Cathode Structure for a Direct Methanol Fuel Cell

    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

  3. New ETFE-based membrane for direct methanol fuel cell

    Saarinen, V.; Kallio, T.; Paronen, M.; Tikkanen, P.; Rauhala, E.; Kontturi, K.

    2005-01-01

    The investigated membranes are based on 35-bar μ m thick commercial poly(ethylene-alt-tetrafluoroethylene) (ETFE) films. The films were made proton conductive by means of irradiation treatment followed by sulfonation. These membranes have exceptionally low water uptake and excellent dimensional stability. The new membranes are investigated widely in a laboratory-scale direct methanol fuel cell (DMFC). The temperature range used in the fuel cell tests was 30-85-bar o C and the measurement results were compared to those of the Nafion ( R)115 membrane. Also methanol permeability through the ETFE-based membrane was measured as a function of temperature, resulting in values less than 10% of the corresponding values for Nafion ( R)115, which was considerably thicker than the experimental membrane. Methanol crossover was reported to decrease when the thickness of the membrane increases, so the ETFE-based membrane compares favourably to Nafion ( R) membranes. The maximum power densities achieved with the experimental ETFE-based membrane were about 40-65% lower than the corresponding values of the Nafion ( R)115 membrane, because of the lower conductivity and noticeably higher IR-losses. Chemical and mechanical stability of the ETFE-based membrane appeared to be promising since it was tested over 2000-bar h in the DMFC without any performance loss

  4. Improved Flow-Field Structures for Direct Methanol Fuel Cells

    Gurau, Bogdan [Nuvant Systems Inc., Crown Point, IN (United States)

    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.

  5. Direct fuel cell - A high proficiency power generator for biofuels

    Patel, P.S.; Steinfeld, G.; Baker, B.S.

    1994-01-01

    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

  6. Experimental investigation two phase flow in direct methanol fuel cells

    Mat, M. D.; Kaplan, Y.; Celik, S.; Oeztural, A.

    2007-01-01

    Direct methanol fuel cells (DMFC) have received many attentions specifically for portable electronic applications since it utilize methanol which is in liquid form in atmospheric condition and high energy density of the methanol. Thus it eliminates the storage problem of hydrogen. It also eliminates humidification requirement of polymeric membrane which is a problem in PEM fuel cells. Some electronic companies introduced DMFC prototypes for portable electronic applications. Presence of carbon dioxide gases due to electrochemical reactions in anode makes the problem a two phase problem. A two phase flow may occur at cathode specifically at high current densities due to the excess water. Presence of gas phase in anode region and liquid phase in cathode region prevents diffusion of fuel and oxygen to the reaction sites thus reduces the performance of the system. Uncontrolled pressure buildup in anode region increases methanol crossover through membrane and adversely effect the performance. Two phase flow in both anode and cathode region is very effective in the performance of DMYC system and a detailed understanding of two phase flow for high performance DMFC systems. Although there are many theoretical and experimental studies available on the DMFC systems in the literature, only few studies consider problem as a two-phase flow problem. In this study, an experimental set up is developed and species distributions on system are measured with a gas chromatograph. System performance characteristics (V-I curves) is measured depending on the process parameters (temperature, fuel ad oxidant flow rates, methanol concentration etc)

  7. Cell phone use and parotid salivary gland alterations: no molecular evidence.

    de Souza, Fabrício T A; Correia-Silva, Jeane F; Ferreira, Efigênia F; Siqueira, Elisa C; Duarte, Alessandra P; Gomez, Marcus Vinícius; Gomez, Ricardo S; Gomes, Carolina C

    2014-07-01

    The association between cell phone use and the development of parotid tumors is controversial. Because there is unequivocal evidence that the microenvironment is important for tumor formation, we investigated in the parotid glands whether cell phone use alters the expression of gene products related to cellular stress. We used the saliva produced by the parotid glands of 62 individuals to assess molecular alterations compatible with cellular stress, comparing the saliva from the gland exposed to cell phone radiation (ipsilateral) to the saliva from the opposite, unexposed parotid gland (contralateral) of each individual. We compared salivary flow, total protein concentration, p53, p21, reactive oxygen species (ROS), and salivary levels of glutathione (GSH), heat shock proteins 27 and 70, and IgA between the ipsilateral and contralateral parotids. No difference was found for any of these parameters, even when grouping individuals by period of cell phone use in years or by monthly average calls in minutes. We provide molecular evidence that the exposure of parotid glands to cell phone use does not alter parotid salivary flow, protein concentration, or levels of proteins of genes that are directly or indirectly affected by heat-induced cellular stress. ©2014 American Association for Cancer Research.

  8. Spermatogonial stem cell transplantation and male infertility: Current status and future directions.

    Forbes, Connor M; Flannigan, Ryan; Schlegel, Peter N

    2018-03-01

    To summarise the current state of research into spermatogonial stem cell (SSC) therapies with a focus on future directions, as SSCs show promise as a source for preserving or initiating fertility in otherwise infertile men. We performed a search for publications addressing spermatogonial stem cell transplantation in the treatment of male infertility. The search engines PubMed and Google Scholar were used from 1990 to 2017. Search terms were relevant for spermatogonial stem cell therapies. Titles of publications were screened for relevance; abstracts were read, if related and full papers were reviewed for directly pertinent original research. In all, 58 papers were found to be relevant to this review, and were included in appropriate subheadings. This review discusses the various techniques that SSCs are being investigated to treat forms of male infertility. Evidence does not yet support clinical application of SSCs in humans. However, significant progress in the in vitro and in vivo development of SSCs, including differentiation into functional germ cells, gives reason for cautious optimism for future research.

  9. Engineering the human pluripotent stem cell microenvironment to direct cell fate.

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Direct fuel cell power plants: the final steps to commercialization

    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

  11. Direct imaging of APP proteolysis in living cells

    Niccoló Parenti

    2017-04-01

    Full Text Available Alzheimer’s disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of Aβ peptide is widely accepted as being one of the main key events triggering the development of Alzheimer’s disease. Aβ peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP. Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue. Kits available commercially measure the enzymatic activity of the secretases from cells lysates, in vitro. By contrast, we have developed a prototypal rapid bioassay that provides visible information on the proteolytic processing of APP directly in living cells. APP was fused to a monomeric variant of the green fluorescent protein and a monomeric variant of the red fluorescent protein at the C-terminal and N-terminal (mChAPPmGFP, respectively. Changes in the proteolytic processing rate in transfected human neuroblastoma and rat neuronal cells were imaged with confocal microscopy as changes in the red/green fluorescence intensity ratio. The significant decrease in the mean red/green ratio observed in cells over-expressing the β-secretase BACE1, or the α-secretase ADAM10, fused to a monomeric blue fluorescent protein confirms that the proteolytic site is still accessible. Specific siRNA was used to evaluate the contribution of endogenous BACE1. Interestingly, we found that the degree of proteolytic processing of APP is not completely homogeneous within the same single cell, and that there is a high degree of variability between cells of the same type. We were also able to follow with a fluorescence spectrometer the changes in the red emission intensity of the extracellular medium when BACE1 was overexpressed. This represents a complementary approach to fluorescence microscopy for rapidly detecting changes in the

  12. First direct evidence of a vertebrate three-level trophic chain in the fossil record.

    Kriwet, Jürgen; Witzmann, Florian; Klug, Stefanie; Heidtke, Ulrich H J

    2008-01-22

    We describe the first known occurrence of a Permian shark specimen preserving two temnospondyl amphibians in its digestive tract as well as the remains of an acanthodian fish, which was ingested by one of the temnospondyls. This exceptional find provides for the first time direct evidence of a vertebrate three-level food chain in the fossil record with the simultaneous preservation of three trophic levels. Our analysis shows that small-sized Lower Permian xenacanthid sharks of the genus Triodus preyed on larval piscivorous amphibians. The recorded trophic interaction can be explained by the adaptation of certain xenacanthids to fully freshwater environments and the fact that in these same environments, large temnospondyls occupied the niche of modern crocodiles. This unique faunal association has not been documented after the Permian and Triassic. Therefore, this Palaeozoic three-level food chain provides strong and independent support for changes in aquatic trophic chain structures through time.

  13. Direct evidence for an orbital magnetic quadrupole twist mode in nuclei

    Reitz, B.; Frekers, D.

    2002-02-01

    The reactions 58 Ni(e,e') and 58 Ni(p,p') have been studied at kinematics favorable for the excitation of J π = 2 - states by isovector spin-flip transitions with ΔL = 1. There are states at an excitation energy E x ∼ 10 MeV which are strongly excited in electron scattering but not in proton scattering, suggesting a predominantly orbital character. This is taken as direct evidence for the so-called twist mode in nuclei in which different layers of nuclear fluid in the upper and lower hemisphere counterrotate against each other. Microscopic quasiparticle-phonon model calculations which predict sizable orbital M2 strength at his excitation energy yield indeed a current flow pattern of the strongest transitions consistent with a twist-like motion. (orig.)

  14. Search for direct evidence for charm in hadronic interactions using a high-resolution bubble chamber

    2002-01-01

    A high-resolution rapid-cycling hydrogen bubble chamber will be used to search for direct evidence of charmed-particle production in $\\sim$350 GeV/c $\\pi^{-}$ interactions. The chamber is 20 cm in diameter and contains $\\sim$1l of liquid hydrogen. The bright field optical system is designed to achieve a resolution in space $\\simeq$ 20-30 $\\mu$m (optical depth of field 2-4 mm), which should allow the detection of charmed-particle decay vertices in complex events if $\\tau_{charm} \\geq 10^{-13}$ sec. An interaction trigger will be used to give an initial sensitivity $\\sim$5-10 events/$\\mu$b for a test run designed primarily to search for the signal and establish a cross-section and approximate lifetime for charm.

  15. Learning through EC directive based SEA in spatial planning? Evidence from the Brunswick Region in Germany

    Fischer, Thomas B.; Kidd, Sue; Jha-Thakur, Urmila; Gazzola, Paola; Peel, Deborah

    2009-01-01

    This paper presents results of an international comparative research project, funded by the UK Economic and Social Research Council (ESRC) and the Academy for Sustainable Communities (ASC) on the 'learning potential of appraisal (strategic environmental assessment - SEA) in spatial planning'. In this context, aspects of 'single-loop' and 'double-loop' learning, as well as of individual, organisational and social learning are discussed for emerging post-EC Directive German practice in the planning region (Zweckverband) of Brunswick (Braunschweig), focusing on four spatial plan SEAs from various administrative levels in the region. It is found that whilst SEA is able to lead to plan SEA specific knowledge acquisition, comprehension, application and analysis ('single-loop learning'), it is currently resulting only occasionally in wider synthesis and evaluation ('double-loop learning'). Furthermore, whilst there is evidence that individual and occasionally organisational learning may be enhanced through SEA, most notably in small municipalities, social learning appears to be happening only sporadically.

  16. First Evidence of pep Solar Neutrinos by Direct Detection in Borexino

    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.

    2012-02-01

    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±0.6stat±0.3systcounts/(day·100ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×108cm-2s-1 and <7.7×108cm-2s-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. Evidence for production of single top quarks and first direct measurement of |Vtb|

    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.

    2006-01-01

    The D0 Collaboration presents first evidence for the production of single top quarks at the Fermilab Tevatron p(bar p) collider. Using a 0.9 fb -1 dataset, we apply a multivariate analysis to separate signal from background and measure σ(p(bar p) → 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 signal is 0.035%, corresponding to a 3.4 standard deviation significance. We use the cross section measurement to directly determine the CKM matrix element that describes the W tb coupling and find 0.68 tb | (le) 1 at 95% C.L

  18. Determinants of foreign direct investment in Lesotho: evidence from cointegration and error correction modeling

    Malefa Rose Malefane

    2013-02-01

    Full Text Available Over the past decade, Lesotho has recorded a substantial increase in levels of foreign direct investment (FDI inflow, part of it prompted by trade privileges. Building on the extant literature, this study provides an empirical analysis of determinants of FDI in Lesotho. The study looks at how macroeconomic stability, regulatory frameworks, political stability and market size affect FDI.  The evidence from this study shows that some of the foreign enterprises in Lesotho are there to serve a bigger South African market. Also, the country has benefited from a more export-oriented investment promotion strategy. Critical issues however remain that must be addressed if the country is to attract more FDI and retain existing investors .These issues pertain to bureaucratic red-tape, corruption and political instability.

  19. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions.

    Wong, Christopher X; Ganesan, Anand N; Selvanayagam, Joseph B

    2017-05-01

    Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  20. Direct real-time neural evidence for task-set inertia.

    Evans, Lisa H; Herron, Jane E; Wilding, Edward L

    2015-03-01

    One influential explanation for the costs incurred when switching between tasks is that they reflect interference arising from completing the previous task-known as task-set inertia. We report a novel approach for assessing task-set inertia in a memory experiment using event-related potentials (ERPs). After a study phase, participants completed a test block in which they switched between a memory task (retrieving information from the study phase) and a perceptual task. These tasks alternated every two trials. An ERP index of the retrieval of study information was evident in the memory task. It was also present on the first trial of the perceptual task but was markedly attenuated on the second. Moreover, this task-irrelevant ERP activity was positively correlated with a behavioral cost associated with switching between tasks. This real-time measure of neural activity thus provides direct evidence of task-set inertia, its duration, and the functional role it plays in switch costs. © The Author(s) 2015.

  1. Direct effects of music in non-auditory cells in culture

    Nathalia dos Reis Lestard

    2013-01-01

    Full Text Available 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.

  2. Network meta-analysis: a technique to gather evidence from direct and indirect comparisons

    2017-01-01

    Systematic reviews and pairwise meta-analyses of randomized controlled trials, at the intersection of clinical medicine, epidemiology and statistics, are positioned at the top of evidence-based practice hierarchy. These are important tools to base drugs approval, clinical protocols and guidelines formulation and for decision-making. However, this traditional technique only partially yield information that clinicians, patients and policy-makers need to make informed decisions, since it usually compares only two interventions at the time. In the market, regardless the clinical condition under evaluation, usually many interventions are available and few of them have been studied in head-to-head studies. This scenario precludes conclusions to be drawn from comparisons of all interventions profile (e.g. efficacy and safety). The recent development and introduction of a new technique – usually referred as network meta-analysis, indirect meta-analysis, multiple or mixed treatment comparisons – has allowed the estimation of metrics for all possible comparisons in the same model, simultaneously gathering direct and indirect evidence. Over the last years this statistical tool has matured as technique with models available for all types of raw data, producing different pooled effect measures, using both Frequentist and Bayesian frameworks, with different software packages. However, the conduction, report and interpretation of network meta-analysis still poses multiple challenges that should be carefully considered, especially because this technique inherits all assumptions from pairwise meta-analysis but with increased complexity. Thus, we aim to provide a basic explanation of network meta-analysis conduction, highlighting its risks and benefits for evidence-based practice, including information on statistical methods evolution, assumptions and steps for performing the analysis. PMID:28503228

  3. Nano-Engineered Catalysts for Direct Methanol Fuel Cells

    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

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

    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.

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

    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

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

    Aggarwal, Leena; Sekhon, Jagmeet S.; Arora, Ashima; Sheet, Goutam, E-mail: goutam@iisermohali.ac.in [Department of Physical Sciences, Indian Institute of Science Education and Research Mohali (IISER M), Sector 81, S. A. S. Nagar, Manauli PO-140306 (India); Guin, Satya N.; Negi, Devendra S.; Datta, Ranjan; Biswas, Kanishka, E-mail: kanishka@jncasr.ac.in [New Chemistry Unit and International Centre for Materials Science, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bangalore 560064 (India)

    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}.

  7. Evidence for direct geographic influences on linguistic sounds: the case of ejectives.

    Caleb Everett

    Full Text Available We present evidence that the geographic context in which a language is spoken may directly impact its phonological form. We examined the geographic coordinates and elevations of 567 language locations represented in a worldwide phonetic database. Languages with phonemic ejective consonants were found to occur closer to inhabitable regions of high elevation, when contrasted to languages without this class of sounds. In addition, the mean and median elevations of the locations of languages with ejectives were found to be comparatively high. The patterns uncovered surface on all major world landmasses, and are not the result of the influence of particular language families. They reflect a significant and positive worldwide correlation between elevation and the likelihood that a language employs ejective phonemes. In addition to documenting this correlation in detail, we offer two plausible motivations for its existence. We suggest that ejective sounds might be facilitated at higher elevations due to the associated decrease in ambient air pressure, which reduces the physiological effort required for the compression of air in the pharyngeal cavity--a unique articulatory component of ejective sounds. In addition, we hypothesize that ejective sounds may help to mitigate rates of water vapor loss through exhaled air. These explications demonstrate how a reduction of ambient air density could promote the usage of ejective phonemes in a given language. Our results reveal the direct influence of a geographic factor on the basic sound inventories of human languages.

  8. Performance of a passive direct ethanol fuel cell

    Pereira, J. P.; Falcão, D. S.; Oliveira, V. B.; Pinto, A. M. F. R.

    2014-06-01

    Ethanol emerges as an attractive fuel since it is less toxic and has higher energy density than methanol and can be produced from biomass. Direct ethanol fuel cells (DEFCs) appear as a good choice for producing sustainable energy for portable applications. However, they are still far from attaining acceptable levels of power output, since their performance is affected by the slow electrochemical ethanol oxidation and water and ethanol crossover. In the present work, an experimental study on the performance of a passive DEFC is described. Tailored MEAs (membrane electrode assembly) with different catalyst loadings, anode diffusion layers and membranes were tested in order to select optimal working conditions at high ethanol concentrations and low ethanol crossover. The performance increased with an increase of membrane and anode diffusion layer thicknesses and anode catalyst loading. A maximum power density of 1.33 mW cm-2, was obtained using a Nafion 117 membrane, 4 mg cm-2 of Pt-Ru and 2 mg cm-2 of Pt on the anode and cathode catalyst layers, ELAT as anode diffusion layer, carbon cloth as cathode diffusion layer and an ethanol concentration of 2 M. As far as the authors are aware this is the first work reporting an experimental optimization of passive DEFCs.

  9. New Catalysts for Direct Methanol Oxidation Fuel Cells

    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.

  10. Modified SPEEK membranes for direct ethanol fuel cell

    Maab, Husnul

    2010-07-01

    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 x 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 x 10(-10) kg m s(-1) m(-2) respectively, which is 2- to 50-fold lower than that for plain SPEEK (19 x 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 degrees C and 90 degrees C. (C) 2010 Elsevier B.V. All rights reserved.

  11. Novel Anode Catalyst for Direct Methanol Fuel Cells

    S. Basri

    2014-01-01

    Full Text Available 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.

  12. Novel anode catalyst for direct methanol fuel cells.

    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.

  13. Novel sex cells and evidence for sex pheromones in diatoms.

    Sato, Shinya; Beakes, Gordon; Idei, Masahiko; Nagumo, Tamotsu; Mann, David G

    2011-01-01

    Diatoms belong to the stramenopiles, one of the largest groups of eukaryotes, which are primarily characterized by a presence of an anterior flagellum with tubular mastigonemes and usually a second, smooth flagellum. Based on cell wall morphology, diatoms have historically been divided into centrics and pennates, of which only the former have flagella and only on the sperm. Molecular phylogenies show the pennates to have evolved from among the centrics. However, the timing of flagellum loss--whether before the evolution of the pennate lineage or after--is unknown, because sexual reproduction has been so little studied in the 'araphid' basal pennate lineages, to which Pseudostaurosira belongs. Sexual reproduction of an araphid pennate, Pseudostaurosira trainorii, was studied with light microscopy (including time lapse observations and immunofluorescence staining observed under confocal scanning laser microscopy) and SEM. We show that the species produces motile male gametes. Motility is mostly associated with the extrusion and retrieval of microtubule-based 'threads', which are structures hitherto unknown in stramenopiles, their number varying from one to three per cell. We also report experimental evidence for sex pheromones that reciprocally stimulate sexualization of compatible clones and orientate motility of the male gametes after an initial 'random walk'. The threads superficially resemble flagella, in that both are produced by male gametes and contain microtubules. However, one striking difference is that threads cannot beat or undulate and have no motility of their own, and they do not bear mastigonemes. Threads are sticky and catch and draw objects, including eggs. The motility conferred by the threads is probably crucial for sexual reproduction of P. trainorii, because this diatom is non-motile in its vegetative stage but obligately outbreeding. Our pheromone experiments are the first studies in which gametogenesis has been induced in diatoms by cell

  14. Novel sex cells and evidence for sex pheromones in diatoms.

    Shinya Sato

    Full Text Available BACKGROUND: Diatoms belong to the stramenopiles, one of the largest groups of eukaryotes, which are primarily characterized by a presence of an anterior flagellum with tubular mastigonemes and usually a second, smooth flagellum. Based on cell wall morphology, diatoms have historically been divided into centrics and pennates, of which only the former have flagella and only on the sperm. Molecular phylogenies show the pennates to have evolved from among the centrics. However, the timing of flagellum loss--whether before the evolution of the pennate lineage or after--is unknown, because sexual reproduction has been so little studied in the 'araphid' basal pennate lineages, to which Pseudostaurosira belongs. METHODS/PRINCIPAL FINDING: Sexual reproduction of an araphid pennate, Pseudostaurosira trainorii, was studied with light microscopy (including time lapse observations and immunofluorescence staining observed under confocal scanning laser microscopy and SEM. We show that the species produces motile male gametes. Motility is mostly associated with the extrusion and retrieval of microtubule-based 'threads', which are structures hitherto unknown in stramenopiles, their number varying from one to three per cell. We also report experimental evidence for sex pheromones that reciprocally stimulate sexualization of compatible clones and orientate motility of the male gametes after an initial 'random walk'. CONCLUSIONS/SIGNIFICANCE: The threads superficially resemble flagella, in that both are produced by male gametes and contain microtubules. However, one striking difference is that threads cannot beat or undulate and have no motility of their own, and they do not bear mastigonemes. Threads are sticky and catch and draw objects, including eggs. The motility conferred by the threads is probably crucial for sexual reproduction of P. trainorii, because this diatom is non-motile in its vegetative stage but obligately outbreeding. Our pheromone experiments

  15. New bimetallic EMF cell shows promise in direct energy conversion

    Hesson, J. C.; Shimotake, H.

    1968-01-01

    Concentration cell, based upon a thermally regenerative cell principle, produces electrical energy from any large heat source. This experimental bimetallic EMF cell uses a sodium-bismuth alloy cathode and a pure liquid sodium anode. The cell exhibits reliability, corrosion resistance, and high current density performance.

  16. Long Term Performance Study of a Direct Methanol Fuel Cell Fed with Alcohol Blends

    Teresa J. Leo; Miguel A. Raso; Emilio Navarro; Eleuterio Mora

    2013-01-01

    The use of alcohol blends in direct alcohol fuel cells may be a more environmentally friendly and less toxic alternative to the use of methanol alone in direct methanol fuel cells. This paper assesses the behaviour of a direct methanol fuel cell fed with aqueous methanol, aqueous ethanol and aqueous methanol/ethanol blends in a long term experimental study followed by modelling of polarization curves. Fuel cell performance is seen to decrease as the ethanol content rises, and subsequent opera...

  17. Optimum Performance of Direct Hydrogen Hybrid Fuel Cell Vehicles

    Zhao, Hengbing; Burke, Andy

    2009-01-01

    Proton Exchange Membrane fuel cell (PEMFC) technology is one of the most attractive candidates for transportation applications due to its inherently high efficiency and high power density. However, the fuel cell system efficiency can suffer because of the need for forced air supply and water-cooling systems. Hence the operating strategy of the fuel cell system can have a significant impact on the fuel cell system efficiency and thus vehicle fuel economy. The key issues are how the fuel cell b...

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

    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.

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

    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…

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

    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

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

    Anna Boss

    2016-08-01

    Full Text Available 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.

  2. Direct Observation of Clinical Skills Feedback Scale: Development and Validity Evidence.

    Halman, Samantha; Dudek, Nancy; Wood, Timothy; Pugh, Debra; Touchie, Claire; McAleer, Sean; Humphrey-Murto, Susan

    2016-01-01

    Construct: This article describes the development and validity evidence behind a new rating scale to assess feedback quality in the clinical workplace. Competency-based medical education has mandated a shift to learner-centeredness, authentic observation, and frequent formative assessments with a focus on the delivery of effective feedback. Because feedback has been shown to be of variable quality and effectiveness, an assessment of feedback quality in the workplace is important to ensure we are providing trainees with optimal learning opportunities. The purposes of this project were to develop a rating scale for the quality of verbal feedback in the workplace (the Direct Observation of Clinical Skills Feedback Scale [DOCS-FBS]) and to gather validity evidence for its use. Two panels of experts (local and national) took part in a nominal group technique to identify features of high-quality feedback. Through multiple iterations and review, 9 features were developed into the DOCS-FBS. Four rater types (residents n = 21, medical students n = 8, faculty n = 12, and educators n = 12) used the DOCS-FBS to rate videotaped feedback encounters of variable quality. The psychometric properties of the scale were determined using a generalizability analysis. Participants also completed a survey to gather data on a 5-point Likert scale to inform the ease of use, clarity, knowledge acquisition, and acceptability of the scale. Mean video ratings ranged from 1.38 to 2.96 out of 3 and followed the intended pattern suggesting that the tool allowed raters to distinguish between examples of higher and lower quality feedback. There were no significant differences between rater type (range = 2.36-2.49), suggesting that all groups of raters used the tool in the same way. The generalizability coefficients for the scale ranged from 0.97 to 0.99. Item-total correlations were all above 0.80, suggesting some redundancy in items. Participants found the scale easy to use (M = 4.31/5) and clear

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

    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

  4. Directional differentiation of chicken embryonic stem cells into ...

    Chicken embryonic stem (ES) cells are useful for producing transgenic chickens and preserving genetic material in avian species. In this study, the differentiation potential of chicken ES cells was investigated in vitro. Chicken ES cells were differentiated into osteoblasts cultured for 15 to 21 days in the induction media ...

  5. Direct evidence for an evolving dust cloud in the exoplanet KIC 12557548 b

    Bochinski, J. J.; Haswell, C. A.; Dhillon, V. S.; Littlefair, S. P.; Marsh, T. R.

    2014-04-01

    We present simultaneous multi-color optical photometry of the transiting exoplanet KIC 12557548 b which reveals, for the first time, the colour dependence of the transit depth. These depths are consistent with dust extinction as observed in the ISM, but require grain sizes comparable to the largest found in the ISM: 0.25μm - 1μm. This provides direct evidence in favour of the disrupting low-mass rocky planet model for this object. Our light curves also give the the highest-quality coverage of individual transits to date. The smooth low amplitude pre-ingress and post-egress features, and the sharp V-shaped transits noted and modelled in the phase-folded Kepler data are probably artefacts of averaging many transits of variable shape. Our light curves reveal instead a step-like shoulder in the egress. The transit shape overall is not too different from that caused by a circular disc of occulting material, suggesting that the bulk of the extincting dust is not significantly elongated along the orbital path. The changing wavelength-dependent transit depth offers an unprecedented opportunity to determine the composition of the disintegrating rocky body KIC 12557548 b. We detected 3 out-of-transit u' band events consistent with stellar flares. These could be signatures of star-planet interactions.

  6. Age Differences in Self-Continuity: Converging Evidence and Directions for Future Research.

    Löckenhoff, Corinna E; Rutt, Joshua L

    2017-06-01

    Life-span development is inherently linked to the perception of time and associated temporal construals. Such concepts are multi-faceted in nature and have important practical implications in areas such as time management, financial planning, or medical choices. A large body of research has documented age-related limitations in global time horizons, but age differences in other aspects of temporal construal are comparatively poorly understood. The present article draws attention to developmental trajectories of self-continuity, defined as perceived associations of one's present self with past and future selves. After considering historical roots and contemporary views on self-continuity, we turn to the life-span developmental literature and review several convergent streams of research that provide indirect evidence for age-related increases in self-continuity. We then consider a small body of recent studies which have directly assessed age differences in self-continuity and summarize our current understanding of this phenomenon including associations between explicit and implicit measures, symmetry between past and future self-continuity, and differentiation from other aspects of time perception. We conclude by highlighting open theoretical questions and considering the practical implications of an increased sense of self-continuity with advancing age. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Direct evidence for GTP and GDP-Pi intermediates in microtubule assembly

    Melki, R.; Carlier, M.F.; Pantaloni, D.

    1990-01-01

    Identification of the kinetic intermediates in GTP hydrolysis on microtubules and characterization of their assembly properties is essential in understanding microtubule dynamics. By using an improved glass filter assay that selectively traps microtubules with a dead time of 2 s and monitoring taxol-induced rapid assembly of microtubules from [γ- 32 P, 3 H]GTP-tubulin 1:1 complex, direct evidence has been obtained for GTP- and GDP-P i -microtubule transient states in the early stages of the polymerization process. A simple kinetic analysis of GTP hydrolysis on microtubules within two sequential pseudo-first-order processes led to apparent first-order rate constants of 0.065 s -1 for the cleavage of the γ-phosphate and 0.02 s -1 for the liberation of P i , assuming a simple random model. Apparent rate constants for GTP hydrolysis and P i release were independent of the composition of the buffer used to polymerize tubulin. The significance of these values with respect to those derived from previous studies from this and other laboratories and the possibility of a vectorial model for GTP hydrolysis are discussed

  8. Direct evidence of the existence of Mn3+ ions in MnTiO3

    Maurya, R. K.; Sharma, Priyamedha; Patel, Ashutosh; Bindu, R.

    2017-08-01

    We investigate the room temperature electronic properties of MnTiO3 synthesised by different preparation conditions. For this purpose, we prepared MnTiO3 under two different cooling rates, one is naturally cooled while the other is quenched in liq.nitrogen. The samples were studied using optical absorbance, photoemission spectroscopy and band structure calculations. We observe significant changes in the structural parameters as a result of quenching. Interestingly, in the parent compound, our combined core level, valence band and optical absorbance studies give evidence of the Mn existence in both 2+ and 3+ states. The fraction of Mn3+ ions has been found to increase on quenching MnTiO3 suggests an increase in oxygen non-stoichiometry. The increase in the fraction of the Mn3+ ions has been manifested a) as slight enhancement in the intensity of the optical absorbance in the visible region. There occurs persistent photo-resistance when the incident light is terminated after shining; b) in the behaviour of the features (close to Fermi level) in the valence band spectra. Hence, the combined analysis of the core level, valence band and optical absorbance spectra suggests that the charge carriers are hole like which further leads to the increase in the electrical conductivity of the quenched sample. The present results provide a recipe to tune the optical absorption in the visible range for its applications in optical sensors, solar cell, etc.

  9. Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.

    Mizoguchi, Takamasa; Ikeda, Shoko; Watanabe, Saori; Sugawara, Michiko; Itoh, Motoyuki

    2017-10-31

    Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1 ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1 ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway. Published under the PNAS license.

  10. Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

    Gupta, Kanupriya; Metgud, Rashmi

    2013-01-01

    Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined. PMID:24455418

  11. Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

    Kanupriya Gupta

    2013-01-01

    Full Text Available Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined.

  12. Calpain-Mediated positional information directs cell wall orientation to sustain plant stem cell activity, growth and development

    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...

  13. Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

    Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

    2005-01-01

    Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

  14. Antitumor Activity of Rat Mesenchymal Stem Cells during Direct or Indirect Co-Culturing with C6 Glioma Cells.

    Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Mel'nikov, P A; Cherepanov, S A; Levinsky, A B; Chehonin, V P

    2016-02-01

    The tumor-suppressive effect of rat mesenchymal stem cells against low-differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other "non-stem" cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell-cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas.

  15. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

    Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

    2017-01-01

    A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform t

  16. Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

    Kathryn L McCabe

    Full Text Available To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs for transplantation in patients with corneal endothelial dystrophies.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.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.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.

  17. Direct-to-consumer stem cell marketing and regulatory responses.

    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.

  18. Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors

    Adriana Bajetto

    2017-10-01

    Full Text Available Glioblastoma (GBM, the most common primary brain tumor in adults, is an aggressive, fast-growing and highly vascularized tumor, characterized by extensive invasiveness and local recurrence. In GBM and other malignancies, cancer stem cells (CSCs are believed to drive invasive tumor growth and recurrence, being responsible for radio- and chemo-therapy resistance. Mesenchymal stem cells (MSCs are multipotent progenitors that exhibit tropism for tumor microenvironment mediated by cytokines, chemokines and growth factors. Initial studies proposed that MSCs might exert inhibitory effects on tumor development, although, to date, contrasting evidence has been provided. Different studies reported either MSC anti-tumor activity or their support to tumor growth. Here, we examined the effects of umbilical cord (UC-MSCs on in vitro GBM-derived CSC growth, by direct cell-to-cell interaction or indirect modulation, via the release of soluble factors. We demonstrate that UC-MSCs and CSCs exhibit reciprocal tropism when co-cultured as 3D spheroids and their direct cell interaction reduces the proliferation of both cell types. Contrasting effects were obtained by UC-MSC released factors: CSCs, cultured in the presence of conditioned medium (CM collected from UC-MSCs, increased proliferation rate through transient ERK1/2 and Akt phosphorylation/activation. Analysis of the profile of the cytokines released by UC-MSCs in the CM revealed a strong production of molecules involved in inflammation, angiogenesis, cell migration and proliferation, such as IL-8, GRO, ENA-78 and IL-6. Since CXC chemokine receptor 2 (CXCR2, a receptor shared by several of these ligands, is expressed in GBM CSCs, we evaluated its involvement in CSC proliferation induced by UC-MSC-CM. Using the CXCR2 antagonist SB225002, we observed a partial but statistically significant inhibition of CSC proliferation and migration induced by the UC-MSC-released cytokines. Conversely, CXCR2 blockade did not

  19. Different Effects of Human Umbilical Cord Mesenchymal Stem Cells on Glioblastoma Stem Cells by Direct Cell Interaction or Via Released Soluble Factors

    Bajetto, Adriana; Pattarozzi, Alessandra; Corsaro, Alessandro; Barbieri, Federica; Daga, Antonio; Bosio, Alessia; Gatti, Monica; Pisaturo, Valerio; Sirito, Rodolfo; Florio, Tullio

    2017-01-01

    Glioblastoma (GBM), the most common primary brain tumor in adults, is an aggressive, fast-growing and highly vascularized tumor, characterized by extensive invasiveness and local recurrence. In GBM and other malignancies, cancer stem cells (CSCs) are believed to drive invasive tumor growth and recurrence, being responsible for radio- and chemo-therapy resistance. Mesenchymal stem cells (MSCs) are multipotent progenitors that exhibit tropism for tumor microenvironment mediated by cytokines, chemokines and growth factors. Initial studies proposed that MSCs might exert inhibitory effects on tumor development, although, to date, contrasting evidence has been provided. Different studies reported either MSC anti-tumor activity or their support to tumor growth. Here, we examined the effects of umbilical cord (UC)-MSCs on in vitro GBM-derived CSC growth, by direct cell-to-cell interaction or indirect modulation, via the release of soluble factors. We demonstrate that UC-MSCs and CSCs exhibit reciprocal tropism when co-cultured as 3D spheroids and their direct cell interaction reduces the proliferation of both cell types. Contrasting effects were obtained by UC-MSC released factors: CSCs, cultured in the presence of conditioned medium (CM) collected from UC-MSCs, increased proliferation rate through transient ERK1/2 and Akt phosphorylation/activation. Analysis of the profile of the cytokines released by UC-MSCs in the CM revealed a strong production of molecules involved in inflammation, angiogenesis, cell migration and proliferation, such as IL-8, GRO, ENA-78 and IL-6. Since CXC chemokine receptor 2 (CXCR2), a receptor shared by several of these ligands, is expressed in GBM CSCs, we evaluated its involvement in CSC proliferation induced by UC-MSC-CM. Using the CXCR2 antagonist SB225002, we observed a partial but statistically significant inhibition of CSC proliferation and migration induced by the UC-MSC-released cytokines. Conversely, CXCR2 blockade did not reduce the

  20. Evident?

    Plant, Peter

    2012-01-01

    Quality assurance and evidence in career guidance in Europe are often seen as self-evident approaches, but particular interests lie behind......Quality assurance and evidence in career guidance in Europe are often seen as self-evident approaches, but particular interests lie behind...

  1. Design and Operation of an Electrochemical Methanol Concentration Sensor for Direct Methanol Fuel Cell Systems

    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.

  2. Ethanol modulates cortical activity: direct evidence with combined TMS and EEG.

    Kähkönen, S; Kesäniemi, M; Nikouline, V V; Karhu, J; Ollikainen, M; Holi, M; Ilmoniemi, R J

    2001-08-01

    The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (EEG) and located using inversion algorithms. Focal magnetic pulses to the left motor cortex were delivered with a figure-of-eight coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity was adjusted to the motor threshold of abductor digiti minimi. Two conditions before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the coil pressed against the scalp; and (2) control condition, with the coil separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control recording of one subject during TMS was made with two bipolar platinum needle electrodes inserted to the left temporal muscle. In each condition, 120 pulses were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG signals was observed at 43 ms after the TMS pulse in the real-TMS condition but not in the control condition or in the control scalp EMG. Potential maps before and after ethanol ingestion were significantly different from each other (P = 0.01), but no differences were found in the control condition. Ethanol changed the TMS-evoked potentials over right frontal and left parietal areas, the underlying effect appearing to be largest in the right prefrontal area. Our findings suggest that ethanol may have changed the functional connectivity between prefrontal and motor cortices. This new noninvasive method provides direct evidence about the modulation of cortical connectivity after ethanol challenge. Copyright 2001 Academic Press.

  3. Direct evidence of plasma - density structuring in the auroral F-region ionosphere

    Tsunoda, R.T.; Haeggstroem, I.; Pellinen-Wannberg, A.; Steen, Aa.; Wannberg, G.

    1985-03-01

    We investigate the hypothesis that large-scale plasma-density enhancements found in the auroral F layer become structured via a magnetic-flux-tube interchange (MFTI) process. In such a process, plasma structure is produced when spatially irregular electric fields transport higher number-density plasma into a region containing lower number-density plasma, and vice versa. Direct experimental evidence of this process can be obtained by measuring concurrently the spatial distributions of F-region plasma density and electric field. Using the tristatic EISCAT radar facility, we measured these quantities in a two-dimensional plane transverse to the geomagnetic field, at 300-km altitude. We show, in a case study, that plasma-density structure found along the poleward wall of a blob was indeed accompanied by similar-scale variations in the ionospheric electric field, and that the sense of relative motion between high- and low-number-density plasma is consistent with ongoing structuring of the plasma via a MFTI process. From the estimated growth rate of 3 x 10 -3 s -1 , the observed plasma structure could have been produced in several minutes by the irregular electic field pattern. The source of the MFTI process, however, is not clear. The MFTI process did not appear to be driven by F-region polarization electric fields, a conclusion based on (1) the apparent lack of inverse correlation between plasma density and 'slip' velocity patterns, and (2) the positive growth rate found along the poleward wall of the blob in the presence of a westward Pedersen current. This conclusion excludes (at least for this data set) the gradient-drift and current-convective instabilities as primary sources of the ongoing structuring process. (Author)

  4. Establishment of a pig fibroblast-derived cell line for locus-directed transgene expression in cell cultures and blastocysts

    Jakobsen, Jannik E; Li, Juan; Moldt, Brian

    2011-01-01

    We report the establishment of a spontaneously immortalized pig cell line designated Pig Flip-in Visualize (PFV) for locus-directed transgene expression in pig cells and blastocysts. The PFV cell line was isolated from pig ear fibroblasts transfected with a Sleeping Beauty DNA transposon-based do......We report the establishment of a spontaneously immortalized pig cell line designated Pig Flip-in Visualize (PFV) for locus-directed transgene expression in pig cells and blastocysts. The PFV cell line was isolated from pig ear fibroblasts transfected with a Sleeping Beauty DNA transposon...

  5. Direct Observation of High-Temperature Superconductivity in One-Unit-Cell FeSe Films

    Zhang Wen-Hao; Zhang Jin-Song; Li Fang-Sen; Guo Ming-Hua; Ding Hao; Tang Chen-Jia; Wang Qing-Yan; He Ke; Ji Shuai-Hua; Chen Xi; Sun Yi; Zhao Yan-Fei; Xing Ying; Wang Hui-Chao; Zhang Hui-Min; Peng Jun-Ping; Li Zhi; Wang Meng; Fujita Takeshi; Hirata Akihiko

    2014-01-01

    We prepared one-unit-cell (1-UC) thick FeSe films on insulating SrTiO 3 substrates with non-superconducting FeTe protection layers by molecular beam epitaxy for ex situ studies. By direct transport and magnetic measurements, we provide definitive evidence for high temperature superconductivity in the 1-UC FeSe films with an onset T C above 40 K and an extremely large critical current density J C ∼1.7×10 6 A/cm 2 at 2 K, which are much higher than T C ∼8 K and J C ∼10 4 A/cm 2 for bulk FeSe, respectively. Our work may pave the way to enhancing and tailoring superconductivity by interface engineering. (express letter)

  6. Conceptual representations in mind and brain: theoretical developments, current evidence and future directions.

    Kiefer, Markus; Pulvermüller, Friedemann

    2012-07-01

    Conceptual representations in long-term memory crucially contribute to perception and action, language and thought. However, the precise nature of these conceptual memory traces is discussed controversially. In particular, the grounding of concepts in the sensory and motor brain systems is the focus of a current debate. Here, we review theoretical accounts of the structure and neural basis of conceptual memory and evaluate them in light of recent empirical evidence. Models of conceptual processing can be distinguished along four dimensions: (i) amodal versus modality-specific, (ii) localist versus distributed, (iii) innate versus experience-dependent, and (iv) stable versus flexible. A systematic review of behavioral and neuroimaging studies in healthy participants along with brain-damaged patients will then be used to evaluate the competing theoretical approaches to conceptual representations. These findings indicate that concepts are flexible, distributed representations comprised of modality-specific conceptual features. Conceptual features are stored in distinct sensory and motor brain areas depending on specific sensory and motor experiences during concept acquisition. Three important controversial issues are highlighted, which require further clarification in future research: the existence of an amodal conceptual representation in the anterior temporal lobe, the causal role of sensory and motor activation for conceptual processing and the grounding of abstract concepts in perception and action. We argue that an embodiment view of conceptual representations realized as distributed sensory and motor cell assemblies that are complemented by supramodal integration brain circuits may serve as a theoretical framework to guide future research on concrete and abstract concepts. Copyright © 2011 Elsevier Srl. All rights reserved.

  7. Method of operating a direct dme fuel cell system

    2011-01-01

    The present invention relates to a method of operating a fuel cell system comprising one or more fuel cells with a proton exchange membrane, wherein the membrane is composed of a polymeric material comprising acid-doped polybenzimidazole (PBI). The method comprises adjusting the operating...

  8. hydrogel membrane as electrolyte for direct borohydride fuel cells

    Administrator

    and hence attractive energy sources for future gene- ration. Among the various types of fuel cells, poly- mer electrolyte fuel cells (PEFCs) are especially promising due to their quick start-up capabilities under ambient conditions. But PEFCs suffer from carbon monoxide poisoning of platinum anode. 1–3 while using reformer ...

  9. Direct sorbitol proton exchange membrane fuel cell using moderate catalyst loadings

    Oyarce, Alejandro; Gonzalez, Carlos; Lima, Raquel Bohn; Lindström, Rakel Wreland; Lagergren, Carina; Lindbergh, Göran

    2014-01-01

    Highlights: •The performance of a direct sorbitol fuel cell was evaluated at different temperatures. •The performance was compared to the performance of a direct glucose fuel cell. •The mass specific peak power density of the direct sorbitol fuel cell was 3.6 mW mg −1 totalcatalystloading at 80 °C. •Both sorbitol and glucose fuel cell suffer from deactivation. -- Abstract: Recent progress in biomass hydrolysis has made it interesting to study the use of sorbitol for electricity generation. In this study, sorbitol and glucose are used as fuels in proton exchange membrane fuel cells having 0.9 mg cm −2 PtRu/C at the anode and 0.3 mg cm −2 Pt/C at the cathode. The sorbitol oxidation was found to have slower kinetics than glucose oxidation. However, at low temperatures the direct sorbitol fuel cell shows higher performance than the direct glucose fuel cell, attributed to a lower degree of catalyst poisoning. The performance of both fuel cells is considerably improved at higher temperatures. High temperatures lower the poisoning, allowing the direct glucose fuel cell to reach a higher performance than the direct sorbitol fuel cell. The mass specific peak power densities of the direct sorbitol and direct glucose fuel cells at 65 °C was 3.2 mW mg −1 catalyst and 3.5 mW mg −1 catalyst , respectively. Both of these values are one order of magnitude larger than mass specific peak power densities of earlier reported direct glucose fuel cells using proton exchange membranes. Furthermore, both the fuel cells showed a considerably decrease in performance with time, which is partially attributed to sorbitol and glucose crossover poisoning the Pt/C cathode

  10. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

    Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore

    2005-01-01

    of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi...

  11. Carbon fuel particles used in direct carbon conversion fuel cells

    Cooper, John F.; Cherepy, Nerine

    2012-10-09

    A system for preparing particulate carbon fuel and using the particulate carbon fuel in a fuel cell. Carbon particles are finely divided. The finely dividing carbon particles are introduced into the fuel cell. A gas containing oxygen is introduced into the fuel cell. The finely divided carbon particles are exposed to carbonate salts, or to molten NaOH or KOH or LiOH or mixtures of NaOH or KOH or LiOH, or to mixed hydroxides, or to alkali and alkaline earth nitrates.

  12. Carbon Fuel Particles Used in Direct Carbon Conversion Fuel Cells

    Cooper, John F.; Cherepy, Nerine

    2008-10-21

    A system for preparing particulate carbon fuel and using the particulate carbon fuel in a fuel cell. Carbon particles are finely divided. The finely dividing carbon particles are introduced into the fuel cell. A gas containing oxygen is introduced into the fuel cell. The finely divided carbon particles are exposed to carbonate salts, or to molten NaOH or KOH or LiOH or mixtures of NaOH or KOH or LiOH, or to mixed hydroxides, or to alkali and alkaline earth nitrates.

  13. Direct Connect Supersonic Combustion Facility (Research Cell 22)

    Federal Laboratory Consortium — Description: RC22 is a continuous-flow, direct-connect supersonic-combustion research facility that is capable of simulating flight conditions from Mach 3.0 to Mach...

  14. Advanced feeder-free generation of induced pluripotent stem cells directly from blood cells.

    Trokovic, Ras; Weltner, Jere; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Salomaa, Veikko; Jalanko, Anu; Otonkoski, Timo; Kyttälä, Aija

    2014-12-01

    Generation of validated human induced pluripotent stem cells (iPSCs) for biobanking is essential for exploring the full potential of iPSCs in disease modeling and drug discovery. Peripheral blood mononuclear cells (PBMCs) are attractive targets for reprogramming, because blood is collected by a routine clinical procedure and is a commonly stored material in biobanks. Generation of iPSCs from blood cells has previously been reported using integrative retroviruses, episomal Sendai viruses, and DNA plasmids. However, most of the published protocols require expansion and/or activation of a specific cell population from PBMCs. We have recently collected a PBMC cohort from the Finnish population containing more than 2,000 subjects. Here we report efficient generation of iPSCs directly from PBMCs in feeder-free conditions in approximately 2 weeks. The produced iPSC clones are pluripotent and transgene-free. Together, these properties make this novel method a powerful tool for large-scale reprogramming of PBMCs and for iPSC biobanking. ©AlphaMed Press.

  15. Direct conversion of human amniotic cells into endothelial cells without transitioning through a pluripotent state

    Ginsberg, Michael; Schachterle, William; Shido, Koji; Rafii, Shahin

    2016-01-01

    Endothelial cells (ECs) have essential roles in organ development and regeneration, and therefore they could be used for regenerative therapies. However, generation of abundant functional endothelium from pluripotent stem cells has been difficult because ECs generated by many existing strategies have limited proliferative potential and display vascular instability. The latter difficulty is of particular importance because cells that lose their identity over time could be unsuitable for therapeutic use. Here, we describe a 3-week platform for directly converting human mid-gestation lineage-committed amniotic fluid–derived cells (ACs) into a stable and expandable population of vascular ECs (rAC-VECs) without using pluripotency factors. By transient expression of the ETS transcription factor ETV2 for 2 weeks and constitutive expression the ETS transcription factors FLI1 and ERG1, concomitant with TGF-β inhibition for 3 weeks, epithelial and mesenchymal ACs are converted, with high efficiency, into functional rAC-VECs. These rAC-VECs maintain their vascular repertoire and morphology over numerous passages in vitro, and they form functional vessels when implanted in vivo. rAC-VECs can be detected in recipient mice months after implantation. Thus, rAC-VECs can be used to establish a cellular platform to uncover the molecular determinants of vascular development and heterogeneity and potentially represent ideal ECs for the treatment of regenerative disorders. PMID:26540589

  16. Functional living biointerfaces to direct cell-material interaction

    Rodrigo Navarro, Aleixandre

    2016-01-01

    [EN] This thesis deals with the development of a living biointerface between synthetic substrates and living cells to engineer cell-material interactions for tissue engineering purposes. This living biointerface is made of Lactococcus lactis, a non-pathogenic lactic bacteria widely used as starter in the dairy industry and, recently, in the expression of heterologous proteins in applications such as oral vaccine delivery or membrane-bound expression of proteins. L. lactis has been engine...

  17. Mis-specified cells die by an active gene-directed process, and inhibition of this death results in cell fate transformation in Drosophila

    Werz, Christian; Lee, Tom V.; Lee, Peter L.; Lackey, Melinda; Bolduc, Clare; Stein, David S.; Bergmann, Andreas

    2009-01-01

    Summary Incorrectly specified or mis-specified cells often undergo cell death or are transformed to adopt a different cell fate during development. The underlying cause for this distinction is largely unknown. In many developmental mutants in Drosophila, large numbers of mis-specified cells die synchronously, providing a convenient model for analysis of this phenomenon. The maternal mutant bicoid is particularly useful model with which to address this issue because its mutant phenotype is a combination of both transformation of tissue (acron to telson) and cell death in the presumptive head and thorax regions. We show that a subset of these mis-specified cells die through an active gene-directed process involving transcriptional upregulation of the cell death inducer hid. Upregulation of hid also occurs in oskar mutants and other segmentation mutants. In hid bicoid double mutants, mis-specified cells in the presumptive head and thorax survive and continue to develop, but they are transformed to adopt a different cell fate. We provide evidence that the terminal torso signaling pathway protects the mis-specified telson tissue in bicoid mutants from hid-induced cell death, whereas mis-specified cells in the head and thorax die, presumably because equivalent survival signals are lacking. These data support a model whereby mis-specification can be tolerated if a survival pathway is provided, resulting in cellular transformation. PMID:16280349

  18. Infrared photoexcitation spectroscopy of conducting polymer and C60 composites: direct evidence of photo-induced electron transfer

    Lee, Kwanghee; Janssen, R.A.J.; Sariciftci, N.S.; Heeger, A.J.

    1994-01-01

    We report direct spectral evidence of photoinduced electron transfer from the excited state of conducting polymer onto C60 by infrared photoexcitation spectroscopy, from 0.01 eV (100 cm-1) to 1.3 eV (11,000 cm-1). The photoinduced absorption spectra of poly(3-octylthiophene) (P30T) and

  19. Tactile motion adaptation reduces perceived speed but shows no evidence of direction sensitivity.

    Sarah McIntyre

    Full Text Available INTRODUCTION: While the directionality of tactile motion processing has been studied extensively, tactile speed processing and its relationship to direction is little-researched and poorly understood. We investigated this relationship in humans using the 'tactile speed aftereffect' (tSAE, in which the speed of motion appears slower following prolonged exposure to a moving surface. METHOD: We used psychophysical methods to test whether the tSAE is direction sensitive. After adapting to a ridged moving surface with one hand, participants compared the speed of test stimuli on the adapted and unadapted hands. We varied the direction of the adapting stimulus relative to the test stimulus. RESULTS: Perceived speed of the surface moving at 81 mms(-1 was reduced by about 30% regardless of the direction of the adapting stimulus (when adapted in the same direction, Mean reduction = 23 mms(-1, SD = 11; with opposite direction, Mean reduction = 26 mms(-1, SD = 9. In addition to a large reduction in perceived speed due to adaptation, we also report that this effect is not direction sensitive. CONCLUSIONS: Tactile motion is susceptible to speed adaptation. This result complements previous reports of reliable direction aftereffects when using a dynamic test stimulus as together they describe how perception of a moving stimulus in touch depends on the immediate history of stimulation. Given that the tSAE is not direction sensitive, we argue that peripheral adaptation does not explain it, because primary afferents are direction sensitive with friction-creating stimuli like ours (thus motion in their preferred direction should result in greater adaptation, and if perceived speed were critically dependent on these afferents' response intensity, the tSAE should be direction sensitive. The adaptation that reduces perceived speed therefore seems to be of central origin.

  20. Nafion®/H-ZSM-5 composite membranes with superior performance for direct methanol fuel cells

    Yildirim, M.H.; Curos, Anna Roca; Motuzas, Julius; Motuzas, J.; Julbe, Anne; Stamatialis, Dimitrios; Wessling, Matthias

    2009-01-01

    Solution cast composite direct methanol fuel cell membranes (DEZ) based on DE2020 Nafion® dispersion and in-house prepared H-ZSM-5 zeolites with different Si/Al ratios were prepared and thoroughly characterized for direct methanol fuel cell (DMFC) applications. All composite membranes have indeed

  1. Direct Utilization of Coal Syngas in High Temperature Fuel Cells

    Celik, Ismail B. [West Virginia University, Morgantown, WV (United States)

    2014-10-30

    This EPSCoR project had two primary goals: (i) to build infrastructure and work force at WVU to support long-term research in the area of fuel cells and related sciences; (ii) study effects of various impurities found in coal-syngas on performance of Solid Oxide Fuel Cells (SOFC). As detailed in this report the WVU research team has made significant accomplishments in both of these areas. What follows is a brief summary of these accomplishments: State-of-the-art test facilities and diagnostic tools have been built and put into use. These include cell manufacturing, half-cell and full-cell test benches, XPS, XRD, TEM, Raman, EDAX, SEM, EIS, and ESEM equipment, unique in-situ measurement techniques and test benches (Environmental EM, Transient Mass-Spectrometer-MS, and IR Optical Temperature measurements). In addition, computational capabilities have been developed culminating in a multi-scale multi-physics fuel cell simulation code, DREAM-SOFC, as well as a Beowulf cluster with 64 CPU units. We have trained 16 graduate students, 10 postdoctoral fellows, and recruited 4 new young faculty members who have actively participated in the EPSCoR project. All four of these faculty members have already been promoted to the tenured associate professor level. With the help of these faculty and students, we were able to secure 14 research awards/contracts amounting to a total of circa $5.0 Million external funding in closely related areas of research. Using the facilities mentioned above, the effects of PH3, HCl, Cl2, and H2S on cell performance have been studied in detail, mechanisms have been identified, and also remedies have been proposed and demonstrated in the laboratory. For example, it has been determined that PH3 reacts rapidly with Ni to from secondary compounds which may become softer or even melt at high temperature and then induce Ni migration to the surface of the cell changing the material and micro-structural properties of the cell drastically. It is found that

  2. Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement.

    Kravchenko-Balasha, Nataly; Shin, Young Shik; Sutherland, Alex; Levine, R D; Heath, James R

    2016-05-17

    Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell-cell signaling can depend on cell-cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell-cell signaling that induces a directed cell-cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell-cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell-cell distances. We show that glioblastoma cell-cell movement can be described as Brownian motion biased by cell-cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

  3. Directed Differentiation of Human Pluripotent Stem Cells to Microglia

    Panagiotis Douvaras

    2017-06-01

    Full Text Available Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs. Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell lines.

  4. Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

    Cristina Sobacchi

    2017-05-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

  5. Manipulation of cell cycle progression can counteract the apparent loss of correction frequency following oligonucleotide-directed gene repair

    Kmiec Eric B

    2007-02-01

    Full Text Available Abstract Background Single-stranded oligonucleotides (ssODN are used routinely to direct specific base alterations within mammalian genomes that result in the restoration of a functional gene. Despite success with the technique, recent studies have revealed that following repair events, correction frequencies decrease as a function of time, possibly due to a sustained activation of damage response signals in corrected cells that lead to a selective stalling. In this study, we use thymidine to slow down the replication rate to enhance repair frequency and to maintain substantial levels of correction over time. Results First, we utilized thymidine to arrest cells in G1 and released the cells into S phase, at which point specific ssODNs direct the highest level of correction. Next, we devised a protocol in which cells are maintained in thymidine following the repair reaction, in which the replication is slowed in both corrected and non-corrected cells and the initial correction frequency is retained. We also present evidence that cells enter a senescence state upon prolonged treatment with thymidine but this passage can be avoided by removing thymidine at 48 hours. Conclusion Taken together, we believe that thymidine may be used in a therapeutic fashion to enable the maintenance of high levels of treated cells bearing repaired genes.

  6. Investigation of in vitro bone cell adhesion and proliferation on Ti using direct current stimulation

    Bodhak, Subhadip; Bose, Susmita; Kinsel, William C.; Bandyopadhyay, Amit

    2012-01-01

    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, was used to study the current stimulation effect on bone cells cultured on conducting Ti samples in vitro. Cell–material 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–material 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. - Highlights: ► D.C. stimulation was used to enhance in vitro bone cell adhesion and proliferation. ► Cells cultured on Ti were stimulated by using a custom made electrical stimulator. ► Optimization was performed by using a varying range of direct currents ∼ 5 to 25 μA. ► 25 μA stimulation was found most beneficial for promotion of cell adhesion/growth.

  7. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes

    Yao Xiao

    2016-09-01

    Full Text Available A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents.

  8. Investigation of Ruthenium Dissolution in Advanced Membrane Electrode Assemblies for Direct Methanol Based Fuel Cells Stacks

    Valdez, T. I.; Firdosy, S.; Koel, B. E.; Narayanan, S. R.

    2005-01-01

    This viewgraph presentation gives a detailed review of the Direct Methanol Based Fuel Cell (DMFC) stack and investigates the Ruthenium that was found at the exit of the stack. The topics include: 1) Motivation; 2) Pathways for Cell Degradation; 3) Cell Duration Testing; 4) Duration Testing, MEA Analysis; and 5) Stack Degradation Analysis.

  9. Characterization of polymer blends PES/SPSf and PES/SPEEK for direct methanol fuel cells

    Manea, G.C.; Mulder, M.H.V.

    2002-01-01

    Existing polymer electrolyte membranes (PEMs) applied for hydrogen fuel cells are frequently not suitable for direct methanol fuel cells due to the high methanol permeability. Therefore, new materials are required and in order to avoid laborious fuel cell experiments with a so-called

  10. Sensing of substratum rigidity and directional migration by fast-crawling cells

    Okimura, Chika; Sakumura, Yuichi; Shimabukuro, Katsuya; Iwadate, Yoshiaki

    2018-05-01

    Living cells sense the mechanical properties of their surrounding environment and respond accordingly. Crawling cells detect the rigidity of their substratum and migrate in certain directions. They can be classified into two categories: slow-moving and fast-moving cell types. Slow-moving cell types, such as fibroblasts, smooth muscle cells, mesenchymal stem cells, etc., move toward rigid areas on the substratum in response to a rigidity gradient. However, there is not much information on rigidity sensing in fast-moving cell types whose size is ˜10 μ m and migration velocity is ˜10 μ m /min . In this study, we used both isotropic substrata with different rigidities and an anisotropic substratum that is rigid on the x axis but soft on the y axis to demonstrate rigidity sensing by fast-moving Dictyostelium cells and neutrophil-like differentiated HL-60 cells. Dictyostelium cells exerted larger traction forces on a more rigid isotropic substratum. Dictyostelium cells and HL-60 cells migrated in the "soft" direction on the anisotropic substratum, although myosin II-null Dictyostelium cells migrated in random directions, indicating that rigidity sensing of fast-moving cell types differs from that of slow types and is induced by a myosin II-related process.

  11. Evidence That Androgens Modulate Human Thymic T Cell Output

    Olsen, Nancy J.; Kovacs, William J.

    2010-01-01

    Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy. Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells (PBMCs). Cells bearing T cell receptor excision circles (TRECs) were quantitated using real-time PCR amplification of DNA isolated from PBMCs from normal men and from hypogonadal men before and after testosterone replacement therapy. Results CD4+CD45+ (“naïve”) T cells comprised 10.5% of lymphocytes in normal males; this proportion was greatly increased in two hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after one month and to 12.51% after 7 months of normalized androgen levels. In two hypogonadal patients TREC levels fell by 83% and 78% after androgen replacement therapy. Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement. PMID:21218609

  12. Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells.

    Kaitsuka, Taku; Tomizawa, Kazuhito

    2015-11-06

    Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

  13. Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells

    Taku Kaitsuka

    2015-11-01

    Full Text Available Protein transduction using cell-penetrating peptides (CPPs is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

  14. Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells.

    Gardell, Jennifer L; Parker, David C

    2017-01-01

    Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

  15. The Effects of Senses of Direction on Wayfinding Behaviors: Evidence from Biking Tourists

    Lin Jo-Hui

    2014-01-01

    Full Text Available The purpose of this study is to examine and observe the effects of senses of direction (i.e., abilities of memory and awareness of orientation on wayfinding behaviors for biking tourists. A total of 295 biking tourists completed a questionnaire using a purposive sampling method. The hierarchical regression model was employed to test the proposed hypotheses. Results show that biking tourists’ abilities of memory and awareness of orientation have a direct effect on their wayfinding behaviors. The contribution of this study is to demonstrate the implication of senses of direction to biking tourists’ wayfinding behaviors and to provide biking tourists suggestions for wayfinding strategies.

  16. CORRUPTION AND FOREIGN DIRECT INVESTMENT. EVIDENCE FROM CENTRAL AND EASTERN EUROPEAN STATES

    Cristina Mihaela Amarandei

    2013-09-01

    Full Text Available This paper examines the impact of corruption on foreign direct investment inflows for ten Central and Eastern European states. The paper attempts to answer the question: what is the role of corruption in attracting foreign direct investments? Using the data from UNCTAD for foreign direct investment and Corruption Perception Index from Transparency International, for a period of 12 years, 2000-2012, we evaluate the specific impact of corruptions on FDI using GDP as control variable. Our results confirm the majority of literature and show a negative significant relation between the variables analyzed, but at a lower intensity than expected.

  17. Foreign Direct Investment and Electronics Exports: Exploratory Empirical Evidence from Malaysia's Top Five Electronics Exports

    Tuck Cheong Tang; Koi Nyen Wong

    2007-01-01

    The foreign direct investment (FDI) has contributed significantly to Malaysia's electronics exports as well as the growth and development of the electronics industry as a result of the export-oriented industrialization initiatives undertaken since 1970s. The aim of this study is to explore the causation between FDI and electronics exports by using Malaysia''s top five electronics exports by SITC (Standard International Trade Classification) product groups. The findings show a bi-directional c...

  18. The Effects of Senses of Direction on Wayfinding Behaviors: Evidence from Biking Tourists

    Lin Jo-Hui; Ho Ching-Hua; Ngan Kok-Lim; Tu Jin-Hua; Weerapaiboon Wongladda

    2014-01-01

    The purpose of this study is to examine and observe the effects of senses of direction (i.e., abilities of memory and awareness of orientation) on wayfinding behaviors for biking tourists. A total of 295 biking tourists completed a questionnaire using a purposive sampling method. The hierarchical regression model was employed to test the proposed hypotheses. Results show that biking tourists’ abilities of memory and awareness of orientation have a direct effect on their wayfinding behaviors. ...

  19. Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.

    Michael C Weiger

    Full Text Available Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF or lysophosphatitic acid (LPA are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.

  20. Characterization of hydrogel printer for direct cell-laden scaffolds

    Whulanza, Yudan; Arsyan, Rendria; Saragih, Agung Shamsuddin

    2018-02-01

    The additive manufacturing technology has been massively developed since the last decade. The technology was previously known as rapid prototyping techniques that aimed to produce a prototyping product in fast and economical way. Currently, this technique is also applied to fabricate microstructure utilized in tissue engineering technology. Here, we introduce a 3D printer which using hydrogel gelatin to realize cell laden scaffold with dimension around 50-100 µm. However, in order to fabricate such a precise dimension, an optimum working parameters are required to control the physical properties of gelatin. At the end of our study, we formulated the best parameters to perform the product as we desired.

  1. Direct evidence that radiation induced micronuclei of early embryos require a mitosis for expression

    Mueller, W.U.; Schlusen, I.; Streffer, C.

    1991-01-01

    The naturally synchronous development of early mouse embryos was exploited to address the question, whether micronuclei require a mitosis for expression or whether they can be expressed in the same cell cycle, in which exposure to X-rays or caffeine took place. Experiments with 2-cell and with 4-cell embryos showed that micronulcei are expressed only if a mitosis is completed. There was no indication, even after doses up to 20 Gy, that micronuclei can be expressed before the mitosis was reached, which followed exposure. Furthermore, no nuclear fragmentation pointing to apoptosis could be detected in the cycle, in which cells were exposed. The same results were obtained when caffeine (5 mM) was used as micronucleus inducing agent. (orig.)

  2. Theory of direct sunlight transmission through orthogonal screen cells

    Aljofi, E.K.

    2006-01-01

    The Purpose of this paper is to investigate the feasibility of using the Rawshan screens to control high light intensity and to avoid excessive solar radiation penetrating inside the building interior. The exploration of the environmental characteristics of this device indicates an ideal solution to utilize available daylight in the arid atmosphere, reduces energy consumption due to the us of artificial light and ensures the continuity of the traditional architecture and the country heritage. A systematic analysis of direct sunlight transmission has been explored using a mathematical approach. The study intends to construct a predictive tool for the architects through which different specifications of the Rawshan screens were identified as far as direct beam of light concerned. The predictive tool was set-up to investigate various parameters of the screen such as the screen configurations, the aperture configurations, the change in orientation and the effect of the sky condition. The analysis of light transmission through the screen were set-up for orthogonal shapes

  3. Characterization of Polyethylene-Graft-Sulfonated Polyarylsulfone Proton Exchange Membranes for Direct Methanol Fuel Cell Applications.

    Kim, Hyung Kyu; Zhang, Gang; Nam, Changwoo; Chung, T C Mike

    2015-12-04

    This paper examines polymer film morphology and several important properties of polyethylene-graft-sulfonated polyarylene ether sulfone (PE-g-s-PAES) proton exchange membranes (PEMs) for direct methanol fuel cell applications. Due to the extreme surface energy differences between a semi-crystalline and hydrophobic PE backbone and several amorphous and hydrophilic s-PAES side chains, the PE-g-s-PAES membrane self-assembles into a unique morphology, with many proton conductive s-PAES channels embedded in the stable and tough PE matrix and a thin hydrophobic PE layer spontaneously formed on the membrane surfaces. In the bulk, these membranes show good mechanical properties (tensile strength >30 MPa, Young's modulus >1400 MPa) and low water swelling (λ 3 mmol/g in the s-PAES domains. On the surface, the thin hydrophobic and semi-crystalline PE layer shows some unusual barrier (protective) properties. In addition to exhibiting higher through-plane conductivity (up to 160 mS/cm) than in-plane conductivity, the PE surface layer minimizes methanol cross-over from anode to cathode with reduced fuel loss, and stops the HO• and HO₂• radicals, originally formed at the anode, entering into PEM matrix. Evidently, the thin PE surface layer provides a highly desirable protecting layer for PEMs to reduce fuel loss and increase chemical stability. Overall, the newly developed PE-g-s-PAES membranes offer a desirable set of PEM properties, including conductivity, selectivity, mechanical strength, stability, and cost-effectiveness for direct methanol fuel cell applications.

  4. Characterization of Polyethylene-Graft-Sulfonated Polyarylsulfone Proton Exchange Membranes for Direct Methanol Fuel Cell Applications

    Hyung Kyu Kim

    2015-12-01

    Full Text Available This paper examines polymer film morphology and several important properties of polyethylene-graft-sulfonated polyarylene ether sulfone (PE-g-s-PAES proton exchange membranes (PEMs for direct methanol fuel cell applications. Due to the extreme surface energy differences between a semi-crystalline and hydrophobic PE backbone and several amorphous and hydrophilic s-PAES side chains, the PE-g-s-PAES membrane self-assembles into a unique morphology, with many proton conductive s-PAES channels embedded in the stable and tough PE matrix and a thin hydrophobic PE layer spontaneously formed on the membrane surfaces. In the bulk, these membranes show good mechanical properties (tensile strength >30 MPa, Young’s modulus >1400 MPa and low water swelling (λ < 15 even with high IEC >3 mmol/g in the s-PAES domains. On the surface, the thin hydrophobic and semi-crystalline PE layer shows some unusual barrier (protective properties. In addition to exhibiting higher through-plane conductivity (up to 160 mS/cm than in-plane conductivity, the PE surface layer minimizes methanol cross-over from anode to cathode with reduced fuel loss, and stops the HO• and HO2• radicals, originally formed at the anode, entering into PEM matrix. Evidently, the thin PE surface layer provides a highly desirable protecting layer for PEMs to reduce fuel loss and increase chemical stability. Overall, the newly developed PE-g-s-PAES membranes offer a desirable set of PEM properties, including conductivity, selectivity, mechanical strength, stability, and cost-effectiveness for direct methanol fuel cell applications.

  5. Development of nanosized electrocatalysts for direct ethanol fuel cells

    Mohamedi, M. [Institut National de la Recherche Scientifique, Varennes, PQ (Canada). Centre de l' Energie, Materiaux et Telecommunications

    2008-07-01

    Fuel cells have been touted as a promising power supply for automotive, portable or stationary use. Although methanol is a strong contender as an alternative fuel, the extensive use of this toxic compound is not practical due to environmental hazards. Ethanol is a good substitute because it has a very positive environmental, health, and safety footprint with no major uncertainties or hazards. Ethanol is a hydrogen-rich liquid which has more energy density than methanol. The C-C bond has a determining effect on fuel cell efficiency and the theoretical energy yield. Therefore, a good electrocatalyst towards the complete oxidation of ethanol must activate the C-C bond breaking while avoiding the poisoning of the catalytic surface by carbon monoxide species that occurs with methanol oxidation. The objective of this study was to develop new catalyst nanoparticles of well-controlled shape, size, and composition with excellent stability and better electrocatalytic activity. This paper described the recent achievements regarding the development of a series of PtxSn100-x catalysts prepared by pulsed laser deposition (PLD). It reported on the effect of several deposition parameters on the structure and properties of the deposited catalysts. It also described how these deposition conditions affect the electrocatalytic response of the resulting materials toward ethanol oxidation. Some interesting periodic oscillations were observed at some catalysts during ethanol electrooxidation. 7 refs., 1 fig.

  6. Burnout and Risk of Cardiovascular Disease: Evidence, Possible Causal Paths, and Promising Research Directions

    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…

  7. Management of Child and Adolescent Eating Disorders: The Current Evidence Base and Future Directions

    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…

  8. The Adaptor Protein SAP Directly Associates with CD3ζ Chain and Regulates T Cell Receptor Signaling

    Proust, Richard; Bertoglio, Jacques; Gesbert, Franck

    2012-01-01

    Mutations altering the gene encoding the SLAM associated protein (SAP) are responsible for the X-linked lymphoproliferative disease or XLP1. Its absence is correlated with a defective NKT cells development, a decrease in B cell functions and a reduced T cells and NK cells cytotoxic activities, thus leading to an immunodeficiency syndrome. SAP is a small 128 amino-acid long protein that is almost exclusively composed of an SH2 domain. It has been shown to interact with the CD150/SLAM family of receptors, and in a non-canonical manner with SH3 containing proteins such as Fyn, βPIX, PKCθ and Nck1. It would thus play the role of a minimal adaptor protein. It has been shown that SAP plays an important function in the activation of T cells through its interaction with the SLAM family of receptors. Therefore SAP defective T cells display a reduced activation of signaling events downstream of the TCR-CD3 complex triggering. In the present work, we evidence that SAP is a direct interactor of the CD3ζ chain. This direct interaction occurs through the first ITAM of CD3ζ, proximal to the membrane. Additionally, we show that, in the context of the TCR-CD3 signaling, an Sh-RNA mediated silencing of SAP is responsible for a decrease of several canonical T cell signaling pathways including Erk, Akt and PLCγ1 and to a reduced induction of IL-2 and IL-4 mRNA. Altogether, we show that SAP plays a central function in the T cell activation processes through a direct association with the CD3 complex. PMID:22912825

  9. Decreased Odds of Injection Risk Behavior Associated With Direct Versus Indirect Use of Syringe Exchange: Evidence From Two California Cities.

    Behrends, Czarina N; Li, Chin-Shang; Gibson, David R

    2017-07-29

    While there is substantial evidence that syringe exchange programs (SEPs) are effective in preventing HIV among people who inject drugs (PWID), nearly all the evidence comes from PWID who obtain syringes from an SEP directly. Much less is known about the benefits of secondary exchange to PWID who get syringes indirectly from friends or acquaintances who visit an SEP for them. We evaluated the effectiveness of direct versus indirect syringe exchange in reducing HIV-related high-risk injecting behavior among PWID in two separate studies conducted in Sacramento and San Jose, California, cities with quite different syringe exchange models. In both studies associations between direct and indirect syringe exchange and self-reported risk behavior were examined with multivariable logistic regression models. Study 1 assessed effects of a "satellite" home-delivery syringe exchange in Sacramento, while Study 2 evaluated a conventional fixed-site exchange in San Jose. Multivariable analyses revealed 95% and 69% reductions, respectively, in high-risk injection associated with direct use of the SEPs in Sacramento and San Jose, and a 46% reduction associated with indirect use of the SEP in Sacramento. Conclusions/Importance: The very large effect of direct SEP use in Sacramento was likely due in part to home delivery of sterile syringes. While more modest effects were associated with indirect use, such use nevertheless is valuable in reducing the risk of HIV transmission of PWID who are unable or unwilling to visit a syringe exchange.

  10. Enhanced micronucleus formation in the descendants of {gamma}-ray-irradiated tobacco cells: Evidence for radiation-induced genomic instability in plant cells

    Yokota, Yuichiro, E-mail: yokota.yuichiro@jaea.go.jp [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Funayama, Tomoo; Hase, Yoshihiro [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Hamada, Nobuyuki [Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae, Tokyo 201-8511 (Japan); Kobayashi, Yasuhiko; Tanaka, Atsushi; Narumi, Issay [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan)

    2010-09-10

    Ionizing radiation-induced genomic instability has been documented in various end points such as chromosomal aberrations and mutations, which arises in the descendants of irradiated mammalian or yeast cells many generations after the initial insult. This study aimed at addressing radiation-induced genomic instability in higher plant tobacco cells. We thus investigated micronucleus (MN) formation and cell proliferation in tobacco cells irradiated with {gamma}-rays and their descendants. In {gamma}-irradiated cells, cell cycle was arrested at G{sub 2}/M phase at around 24 h post-irradiation but released afterward. In contrast, MN frequency peaked at 48 h post-irradiation. Almost half of 40 Gy-irradiated cells had MN at 48 h post-irradiation, but proliferated as actively as sham-irradiated cells up to 120 h post-irradiation. Moreover, the descendants that have undergone at least 22 generations after irradiation still showed a two-fold MN frequency compared to sham-irradiated cells. This is the direct evidence for radiation-induced genomic instability in tobacco cells.

  11. Floodplain Condition and Water Framework Directive River Classification in England: Evidence of a Disconnect.

    Bentley, S.

    2017-12-01

    The European Union Water Framework Directive came into force in October 2000 committing European Union member states to achieve Good Ecological Status for all water bodies. By 2015 29% of rivers across England had achieved this level suggesting that these watercourse units are now functioning well. This study utilises recently published land cover data for England clipped to the floodplain boundary as defined by the 100 year return period discharge to examine the state of valley bottom vegetation and function for these Good Status rivers. Agricultural use of floodplain areas is high with cereal and horticulture covering an average of 24% and pasture accounting for some 37% of the area. Maximum values increase to 77% and 92% respectively. In all cases wetland accounts for less than 2% of the floodplain and rough grassland averages 7%. Such significant and widespread alteration to floodplain vegetation character suggests that the ecological functioning of this component of the fluvial system has been severely negatively impacted calling into question the Water Framework Directive status level. This is a fault of the Water Framework Directive process which only explicitly evaluates the hydromorphological component of the fluvial system for high status rivers preferring to infer functioning from biological indicators that are focused on in-channel assessments. The fundamental omission of floodplain condition in the Water Framework Directive process will result in only partial achievement of the original goals of the Directive with the majority of Europe's floodplains remaining in a highly degraded, non-functional state.

  12. Cytocompatibility of direct water synthesized cadmium selenide quantum dots in colo-205 cells

    Rodriguez-Torres, Marcos R. [Universidad Metropolitana, Nanomaterials Science Laboratory, School of Science and Technology (United States); Velez, Christian; Zayas, Beatriz [Universidad Metropolitana, ChemTox Laboratory, School of Environmental Affairs (United States); Rivera, Osvaldo [Universidad Metropolitana, Nanomaterials Science Laboratory, School of Science and Technology (United States); Arslan, Zikri [Jackson State University, Department of Chemistry (United States); Gonzalez-Vega, Maxine N. [Universidad Metropolitana, Nanomaterials Science Laboratory, School of Science and Technology (United States); Diaz-Diestra, Daysi; Beltran-Huarac, Juan; Morell, Gerardo [University of Puerto Rico, Molecular Science Research Center (United States); Primera-Pedrozo, Oliva M., E-mail: oprimera1@suagm.edu [Universidad Metropolitana, Nanomaterials Science Laboratory, School of Science and Technology (United States)

    2015-06-15

    Cadmium selenide quantum dots (CdSe QDs), inorganic semiconducting nanocrystals, are alluring increased attraction due to their highly refined chemistry, availability, and super tunable optical properties suitable for many applications in different research areas, such as photovoltaics, light-emitting devices, environmental sciences, and nanomedicine. Specifically, they are being widely used in bio-imaging in contrast to organic dyes due to their high brightness and improved photo-stability, and their ability to tune their absorption and emission spectra upon changing the crystal size. The production of CdSe QDs is mostly assisted by trioctylphosphine oxide compound, which acts as solvent or solubilizing agent and renders the QDs soluble in organic compounds (such as toluene, chloroform, and hexane) that are highly toxic. To circumvent the toxicity-related factor in CdSe QDs, we report the synthesis of CdSe QDs capped with thioglycolic acid (TGA) in an aqueous medium, and their biocompatibility in colo-205 cancer cells. In this study, the [Cd{sup 2+}]/[TGA] ratio was adjusted to 11:1 and the Se concentration (10 and 15 mM) was monitored in order to evaluate its influence on the optical properties and cytocompatibility. QDs resulted to be quite stable in water (after purification) and RPMI cell medium and no precipitation was observed for long contact times, making them appealing for in vitro experiments. The spectroscopy analysis, advanced electron microscopy, and X-ray diffractometry studies indicate that the final products were successfully formed exhibiting an improved optical response. Colo-205 cells being exposed to different concentrations of TGA-capped CdSe QDs for 12, 24, and 48 h with doses ranging from 0.5 to 2.0 mM show high tolerance reaching cell viabilities as high as 93 %. No evidence of cellular apoptotic pathways was observed as pointed out by our Annexin V assays at higher concentrations. Moreover, confocal microscopy analysis conducted to

  13. STIM1-Directed Reorganization of Microtubules in Activated Mast Cells

    Hájková, Zuzana; Bugajev, Viktor; Dráberová, Eduarda; Vinopal, Stanislav; Dráberová, Lubica; Janáček, Jiří; Dráber, Petr; Dráber, Pavel

    2011-01-01

    Roč. 186, č. 2 (2011), s. 913-923 ISSN 0022-1767 R&D Projects: GA ČR(CZ) GD204/09/H084; GA ČR GA204/09/1777; GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA MŠk LC545; GA MŠk(CZ) LC06063; GA AV ČR KAN200520701 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50110509 Keywords : STIM1 * bone marrow-derived mast cells * microtubules Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.788, year: 2011

  14. A mathematical model for eph/ephrin-directed segregation of intermingled cells.

    Rotem Aharon

    Full Text Available Eph receptors, the largest family of receptor tyrosine kinases, control cell-cell adhesion/de-adhesion, cell morphology and cell positioning through interaction with cell surface ephrin ligands. Bi-directional signalling from the Eph and ephrin complexes on interacting cells have a significant role in controlling normal tissue development and oncogenic tissue patterning. Eph-mediated tissue patterning is based on the fine-tuned balance of adhesion and de-adhesion reactions between distinct Eph- and ephrin-expressing cell populations, and adhesion within like populations (expressing either Eph or ephrin. Here we develop a stochastic, Lagrangian model that is based on Eph/ephrin biology: incorporating independent Brownian motion to describe cell movement and a deterministic term (the drift term to represent repulsive and adhesive interactions between neighbouring cells. Comparison between the experimental and computer simulated Eph/ephrin cell patterning events shows that the model recapitulates the dynamics of cell-cell segregation and cell cluster formation. Moreover, by modulating the term for Eph/ephrin-mediated repulsion, the model can be tuned to match the actual behaviour of cells with different levels of Eph expression or activity. Together the results of our experiments and modelling suggest that the complexity of Eph/ephrin signalling mechanisms that control cell-cell interactions can be described well by a mathematical model with a single term balancing adhesion and de-adhesion between interacting cells. This model allows reliable prediction of Eph/ephrin-dependent control of cell patterning behaviour.

  15. Evidence for age-related equivalence in the directed forgetting paradigm.

    Gamboz, Nadia; Russo, Riccardo

    2002-01-01

    The directed forgetting paradigm involves, under particular experimental circumstances, inhibitory mechanisms, which operate to the successful forgetting of irrelevant words. The item-by-item cueing method (e.g., Basden & Basden, 1996) was used to investigate the directed forgetting effect in young and old adults. Processing of the experimental words was manipulated between subjects by asking participants to perform either a deep or a shallow orienting task on each word of the study list before the occurrence of the cue (to remember of to forget). Results indicated that the instruction to process deeply both to-be-remembered and to-be-forgotten words led to equivalent directed forgetting effects in young and old adults. These results are discussed with respect to the implications they have for the Inhibitory Deficit theory (e.g., Hasher & Zacks, 1988), which suggests that cognitive aging is mainly characterized by a reduction in the efficiency of inhibitory processes.

  16. Evidence of Self-Directed Learning on a High School Robotics Team

    Nathan R. Dolenc

    2014-12-01

    Full Text Available Self-directed learning is described as an individual taking the initiative to engage in a learning experience while assuming responsibility to follow through to its conclusion. Robotics competitions are examples of informal environments that can facilitate self-directed learning. This study examined how mentor involvement, student behavior, and physical workspace contributed to self-directed learning on one robotics competition team. How did mentors transfer responsibility to students? How did students respond to managing a team? Are the physical attributes of a workspace important? The mentor, student, and workplace factors captured in the research showed mentors wanting students to do the work, students assuming leadership roles, and the limited workspace having a positive effect on student productivity.

  17. Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks.

    Brandon, Mark P; Koenig, Julie; Leutgeb, Stefan

    2014-03-01

    The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type-the place cell. We therefore suggest that parallel information processing in different classes of cells-as is typically observed at lower levels of sensory processing-continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.

  18. Direct Evidence of Mg Incorporation Pathway in Vapor-Liquid-Solid Grown p-type Nonpolar GaN Nanowires

    Patsha, Avinash; Amirthapandian, S.; Pandian, Ramanathaswamy; Bera, S.; Bhattacharya, Anirban; Dhara, Sandip

    2015-01-01

    Doping of III-nitride based compound semiconductor nanowires is still a challenging issue to have a control over the dopant distribution in precise locations of the nanowire optoelectronic devices. Knowledge of the dopant incorporation and its pathways in nanowires for such devices is limited by the growth methods. We report the direct evidence of incorporation pathway for Mg dopants in p-type nonpolar GaN nanowires grown via vapour-liquid-solid (VLS) method in a chemical vapour deposition te...

  19. Global evidence directing regional preventive strategies in Southeast Asia for fighting TB/HIV.

    Aung, Myo Nyein; Moolphate, Saiyud; Paudel, Damodar; Jayathunge Ph, Mangalasiri; Duangrithi, Duangjai; Wangdi, Kinley; Aung, Thin Nyein Nyein; Lorga, Thaworn; Higuchi, Kazue

    2013-03-14

    Tuberculosis (TB) and human immunodeficiency virus (HIV) co-epidemics form a huge burden of disease in the Southeast Asia region. Five out of eleven nations in this region are high TB/HIV burden countries: Myanmar, Thailand, India, Indonesia and Nepal. The trends of TB incidence in these countries have been rising in recent years, in contrast to a falling global trend. Experts in the field of TB control and health service providers have been perplexed by the association of TB and HIV infections which causes a mosaic clinical presentation, a unique course with poor treatment outcomes including death. We conducted a review of contemporary evidence relating to TB/HIV control with the aims of assisting integrated health system responses in Southeast Asia and demystifying current evidence to facilitate translating it into practice.

  20. Direct evidence for a thermal effect of Ar+ ion bombardment in a conventional sputtering mode

    Okuyama, F.; Fujimoto, Y.

    1986-01-01

    Evidence is presented that the Ar + ion bombardment for sputtering in Auger electron spectroscopy can heat the target up to 2000 0 C if the target has poor heat conduction. Polycrystalline microneedles of Cr exhibited spherical tips after being exposed to 3 keV Ar + ions, proving that the needle tips were melted by impacting Ar + ions. Microneedles of Mo ion bombarded under the same condition were bent plastically, which perhaps reflects the thermal annealing of the needles during ion bombardment

  1. How to prevent burnout in cardiologists? A review of the current evidence, gaps, and future directions.

    Panagioti, Maria; Geraghty, Keith; Johnson, Judith

    2018-01-01

    Burnout is rising in all physicians, and cardiologists are not an exemption. Cardiology is a very popular specialty among medical students as it is associated with outstanding training standards and high prestige and income. In this review, we critically summarize the evidence on consequences, causes, and evidence-based interventions for burnout with a view toward recommending the best strategies for promoting wellness in cardiologists. Only a handful of studies have examined burnout specifically in cardiologists. Evidence therefore was mainly extrapolated by larger studies in all physicians and other physician specialties. Burnout in cardiologists has serious negative personal and professional consequences and is associated with suboptimal healthcare outcomes for patients. Burnout in cardiologists is primarily driven by professional and healthcare system demands and inefficiencies such as excessive workload and role complexity, training and certification demands, inefficient compensation models and lack of resources, computerization, and loss of autonomy. Moreover, loss of connectedness with patients, difficulties in balancing work and personal life and overvaluing compulsiveness and perfectionism in medical practice further increase the risk for burnout. Burnout among cardiologists may be best mitigated by organizational strategies complemented by individual stress reduction and reflection techniques under the resilience-based approach. Large-scale strategies are needed to mitigate burnout and promote physician wellness as a shared responsibility of healthcare systems and individuals and be committed in creating a new culture in medicine. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice

    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

  3. Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice.

    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.

  4. Quantifying the weight of fingerprint evidence through the spatial relationship, directions and types of minutiae observed on fingermarks.

    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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Intentional Forgetting Reduces Color-Naming Interference: Evidence from Item-Method Directed Forgetting

    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…

  6. Phonetic Category Cues in Adult-Directed Speech: Evidence from Three Languages with Distinct Vowel Characteristics

    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…

  7. New forms of work organisations, direct and indirect worker participation. Evidence from the Netherlands

    Drucker, Michiel; Looise, Jan C.; Garibaldo, F.; Telljohan, V.

    2004-01-01

    The paper starts with a brief introduction of the ideas with respect to the connection between the introduction of new forms of work organisation and direct and indirect participation (section 2). To show that these ideas are not just theory, but sometimes are realised in practice, we add to this

  8. A high selectivity quaternized polysulfone membrane for alkaline direct methanol fuel cells

    Abuin, GC

    2015-04-01

    Full Text Available polysulfone membrane for alkaline direct methanol fuel cells Graciela C. Abuina, Esteban A. Franceschinib, Patrick Nonjolac, Mkhulu K. Mathec, Mmalewane Modibedic, Horacio R. Cortib,* aCentro de Procesos Superficiales, Instituto Nacional de Tecnología...

  9. Micropump Fuel Mix Control for Novel Miniature Direct Methanol Fuel Cells, Phase I

    National Aeronautics and Space Administration — The Energies and Power Densities of Direct Methanol Fuel Cells (DMFCs) are limited by the size and weight associated with the liquid pump, which must circulate the...

  10. Porous carbon as electrode material in direct ethanol fuel cells (DEFCs) synthesized by the direct carbonization of MOF-5

    Khan, Inayatali

    2014-01-12

    Porous carbon (PC-900) was prepared by direct carbonization of porous metal-organic framework (MOF)-5 (Zn4O(bdc)3, bdc=1,4-benzenedicarboxylate) at 900 °C. The carbon material was deposited with PtM (M=Fe, Ni, Co, and Cu (20 %) metal loading) nanoparticles using the polyol reduction method, and catalysts PtM/PC-900 were designed for direct ethanol fuel cells (DEFCs). However, herein, we are reporting PtFe/PC-900 catalyst combination which has exhibited superior performance among other options. This catalyst was characterized by powder XRD, high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and selected area electron diffraction (SAED) technique. The electrocatalytic capability of the catalyst for ethanol electrooxidation was investigated using cyclic voltammetry and direct ethanol single cell testing. The results were compared with those of PtFe and Pt supported on Vulcan XC72 carbon catalysts (PFe/CX-72 and Pt/XC-72) prepared via the same method. It has been observed that the catalyst PtFe/PC-900 developed in this work showed an outstanding normalized activity per gram of Pt (6.8 mA/g Pt) and superior power density (121 mW/cm2 at 90 °C) compared to commercially available carbon-supported catalysts. © Springer-Verlag Berlin Heidelberg 2014.

  11. Porous carbon as electrode material in direct ethanol fuel cells (DEFCs) synthesized by the direct carbonization of MOF-5

    Khan, Inayatali; Badshah, Amin; Haider, Naghma; Ullah, Shafiq; Anjum, Dalaver H.; Nadeem, Muhammad Arif

    2014-01-01

    Porous carbon (PC-900) was prepared by direct carbonization of porous metal-organic framework (MOF)-5 (Zn4O(bdc)3, bdc=1,4-benzenedicarboxylate) at 900 °C. The carbon material was deposited with PtM (M=Fe, Ni, Co, and Cu (20 %) metal loading) nanoparticles using the polyol reduction method, and catalysts PtM/PC-900 were designed for direct ethanol fuel cells (DEFCs). However, herein, we are reporting PtFe/PC-900 catalyst combination which has exhibited superior performance among other options. This catalyst was characterized by powder XRD, high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and selected area electron diffraction (SAED) technique. The electrocatalytic capability of the catalyst for ethanol electrooxidation was investigated using cyclic voltammetry and direct ethanol single cell testing. The results were compared with those of PtFe and Pt supported on Vulcan XC72 carbon catalysts (PFe/CX-72 and Pt/XC-72) prepared via the same method. It has been observed that the catalyst PtFe/PC-900 developed in this work showed an outstanding normalized activity per gram of Pt (6.8 mA/g Pt) and superior power density (121 mW/cm2 at 90 °C) compared to commercially available carbon-supported catalysts. © Springer-Verlag Berlin Heidelberg 2014.

  12. Intracellular Position of Centrioles and the Direction of Homeostatic Epithelial Cell Movements in the Mouse Cornea.

    Silverman, Erika; Zhao, Jin; Merriam, John C; Nagasaki, Takayuki

    2017-02-01

    Corneal epithelial cells exhibit continuous centripetal movements at a rate of about 30 µm per day, but neither the driving force nor the mechanism that determines the direction of movements is known. To facilitate the investigation of homeostatic cell movement, we examined if the intracellular position of a centriole can be used as a directional marker of epithelial cell movements in the mouse cornea. A direction of cell movements was estimated in fixed specimens from a pattern of underlying subepithelial nerve fibers. Intracellular position of centrioles was determined by gamma-tubulin immunohistology and plotted in a narrow strip along the entire diameter of a cornea from limbus to limbus. When we determined the position of centrioles in the peripheral cornea where cell movements proceed generally along a radial path, about 55% of basal epithelial cells contained a centriole in the front half of a cell. However, in the central cornea where cells exhibit a spiral pattern of movements, centrioles were distributed randomly. These results suggest that centrioles tend to be positioned toward the direction of movement in corneal basal epithelial cells when they are moving centripetally at a steady rate.

  13. Direct contact with endoderm-like cells efficiently induces cardiac progenitors from mouse and human pluripotent stem cells.

    Hideki Uosaki

    Full Text Available RATIONALE: Pluripotent stem cell-derived cardiac progenitor cells (CPCs have emerged as a powerful tool to study cardiogenesis in vitro and a potential cell source for cardiac regenerative medicine. However, available methods to induce CPCs are not efficient or require high-cost cytokines with extensive optimization due to cell line variations. OBJECTIVE: Based on our in-vivo observation that early endodermal cells maintain contact with nascent pre-cardiac mesoderm, we hypothesized that direct physical contact with endoderm promotes induction of CPCs from pluripotent cells. METHOD AND RESULT: To test the hypothesis, we cocultured mouse embryonic stem (ES cells with the endodermal cell line End2 by co-aggregation or End2-conditioned medium. Co-aggregation resulted in strong induction of Flk1(+ PDGFRa(+ CPCs in a dose-dependent manner, but the conditioned medium did not, indicating that direct contact is necessary for this process. To determine if direct contact with End2 cells also promotes the induction of committed cardiac progenitors, we utilized several mouse ES and induced pluripotent (iPS cell lines expressing fluorescent proteins under regulation of the CPC lineage markers Nkx2.5 or Isl1. In agreement with earlier data, co-aggregation with End2 cells potently induces both Nkx2.5(+ and Isl1(+ CPCs, leading to a sheet of beating cardiomyocytes. Furthermore, co-aggregation with End2 cells greatly promotes the induction of KDR(+ PDGFRa(+ CPCs from human ES cells. CONCLUSIONS: Our co-aggregation method provides an efficient, simple and cost-effective way to induce CPCs from mouse and human pluripotent cells.

  14. From algorithmic computing to direct retrieval: evidence from number and alphabetic arithmetic in children and adults.

    Barrouillet, P; Fayol, M

    1998-03-01

    A number of theories of mental arithmetic suggest that the ability to solve simple addition and subtraction problems develops from an algorithmic strategy toward a strategy based on the direct retrieval of the result from memory. In the experiment presented here, 2nd and 12th graders were asked to solve two tasks of number and alphabet arithmetic. The subjects transformed series of 1 to 4 numbers or letters (item span) by adding or subtracting an operand varying from 1 to 4 (operation span). Although both the item and operation span were associated with major and identical effects in the case of both numbers and letters at 2nd grade, such effects were clearly observable only in the case of letters for the adult subjects. This suggests the use of an algorithmic strategy for both types of material in the case of the children and for the letters only in the case of the adults, who retrieved numerical results directly from memory.

  15. Alcohol Marketing on Twitter and Instagram: Evidence of Directly Advertising to Youth/Adolescents.

    Barry, Adam E; Bates, Austin M; Olusanya, Olufunto; Vinal, Cystal E; Martin, Emily; Peoples, Janiene E; Jackson, Zachary A; Billinger, Shanaisa A; Yusuf, Aishatu; Cauley, Daunte A; Montano, Javier R

    2016-07-01

    Assess whether alcohol companies restrict youth/adolescent access, interaction, and exposure to their marketing on Twitter and Instagram. Employed five fictitious male and female Twitter (n = 10) and Instagram (n = 10) user profiles aged 13, 15, 17, 19 and/or 21. Using cellular smartphones, we determined whether profiles could (a) interact with advertising content-e.g. retweet, view video or picture content, comment, share URL; and/or (b) follow and directly receive advertising material updates from the official Instagram and Twitter pages of 22 alcohol brands for 30 days. All user profiles could fully access, view, and interact with alcohol industry content posted on Instagram and Twitter. Twitter's age-gate, which restricts access for those under 21, successfully prevented underage profiles from following and subsequently receiving promotional material/updates. The two 21+ profiles collectively received 1836 alcohol-related tweets within 30 days. All Instagram profiles, however, were able to follow all alcohol brand pages and received an average of 362 advertisements within 30 days. The quantity of promotional updates increased throughout the week, reaching their peak on Thursday and Friday. Representatives/controllers of alcohol brand Instagram pages would respond directly to our underage user's comments. The alcohol industry is in violation of their proposed self-regulation guidelines for digital marketing communications on Instagram. While Twitter's age-gate effectively blocked direct to phone updates, unhindered access to post was possible. Everyday our fictitious profiles, even those as young as 13, were bombarded with alcohol industry messages and promotional material directly to their smartphones. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  16. Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions

    Schiöth, Helgi B.; Craft, Suzanne; Brooks, Samantha J.; Frey, William H.; Benedict, Christian

    2011-01-01

    Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood–brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes as...

  17. Preventing malaria in pregnancy through community-directed interventions: evidence from Akwa Ibom State, Nigeria

    Ishola Gbenga

    2011-08-01

    Full Text Available Abstract Background Despite massive anti-malaria campaigns across the subcontinent, effective access to intermittent preventive treatment (IPTp and insecticide-treated nets (ITNs among pregnant women remain low in large parts of sub-Saharan Africa. The slow uptake of malaria prevention products appears to reflect lack of knowledge and resistance to behavioural change, as well as poor access to resources, and limited support of programmes by local communities and authorities. Methods A recent community-based programme in Akwa Ibom State, Nigeria, is analysed to determine the degree to which community-directed interventions can improve access to malaria prevention in pregnancy. Six local government areas in Southern Nigeria were selected for a malaria in pregnancy prevention intervention. Three of these local government areas were selected for a complementary community-directed intervention (CDI programme. Under the CDI programme, volunteer community-directed distributors (CDDs were appointed by each village and kindred in the treatment areas and trained to deliver ITNs and IPTp drugs as well as basic counseling services to pregnant women. Findings Relative to women in the control area, an additional 7.4 percent of women slept under a net during pregnancy in the treatment areas (95% CI [0.035, 0.115], p-value Conclusion The presented results suggest that the inclusion of community-based programmes can substantially increase effective access to malaria prevention, and also increase access to formal health care access in general, and antenatal care attendance in particular in combination with supply side interventions. Given the relatively modest financial commitments they require, community-directed programmes appear to be a cost-effective way to improve malaria prevention; the participatory approach underlying CDI programmes also promises to strengthen ties between the formal health sector and local communities.

  18. External Finance and the Foreign Direct Investment Decision: Evidence from Privately-Owned-Enterprises in China

    Duanmu, J-L

    2015-01-01

    Access to external finance is found to be a statistically significant factor explaining the probability of privately owned enterprises (POEs) in China undertaking foreign direct investment (FDI). The significance of external finance is magnified in industries featuring a heavy dependence on external finance, high technology, low tangibility, and high inventory. The external finance and FDI linkage is weaker for POEs with group affiliation, but stronger for those with generous employment welfa...

  19. Evidence for transmission of bluetongue virus serotype 26 through direct contact.

    Carrie Batten

    Full Text Available The aim of this study was to assess the mechanisms of transmission of bluetongue virus serotype 26 (BTV-26 in goats. A previous study, which investigated the pathogenicity and infection kinetics of BTV-26 in goats, unexpectedly revealed that one control goat may have been infected through a direct contact transmission route. To investigate the transmission mechanisms of BTV-26 in more detail an experimental infection study was carried out in which three goats were infected with BTV-26, three goats were kept uninfected, but were housed in direct contact with the infected goats, and an additional four goats were kept in indirect contact separated from infected goats by metal gates. This barrier allowed the goats to have occasional face-to-face contact in the same airspace, but feeding, watering, sampling and environmental cleaning was carried out separately. The three experimentally infected goats did not show clinical signs of BTV, however high levels of viral RNA were detected and virus was isolated from their blood. At 21 dpi viral RNA was detected in, and virus was isolated from the blood of the three direct contact goats, which also seroconverted. The four indirect barrier contact goats remained uninfected throughout the duration of the experiment. In order to assess replication in a laboratory model species of Culicoides biting midge, more than 300 Culicoides sonorensis were fed a BTV-26 spiked blood meal and incubated for 7 days. The dissemination of BTV-26 in individual C. sonorensis was inferred from the quantity of virus RNA and indicated that none of the insects processed at day 7 possessed transmissible infections. This study shows that BTV-26 is easily transmitted through direct contact transmission between goats, and the strain does not seem to replicate in C. sonorensis midges using standard incubation conditions.

  20. 1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells.

    Okolotowicz, Karl J; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Mercola, Mark; Cashman, John R

    2015-09-01

    Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure-activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Comparative exergy analysis of direct alcohol fuel cells using fuel mixtures

    Leo Mena, Teresa de Jesus; Raso García, Miguel Ángel; Navarro Arevalo, Emilio; Sánchez de la Blanca, Emilia

    2011-01-01

    Within the last years there has been increasing interest in direct liquid fuel cells as power sources for portable devices and, in the future, power plants for electric vehicles and other transport media as ships will join those applications. Methanol is considerably more convenient and easy to use than gaseous hydrogen and a considerable work is devoted to the development of direct methanol fuel cells. But ethanol has much lower toxicity and from an ecological viewpoint ethanol is exceptiona...

  2. Long Term Performance Study of a Direct Methanol Fuel Cell Fed with Alcohol Blends

    Eleuterio Mora

    2013-01-01

    Full Text Available The use of alcohol blends in direct alcohol fuel cells may be a more environmentally friendly and less toxic alternative to the use of methanol alone in direct methanol fuel cells. This paper assesses the behaviour of a direct methanol fuel cell fed with aqueous methanol, aqueous ethanol and aqueous methanol/ethanol blends in a long term experimental study followed by modelling of polarization curves. Fuel cell performance is seen to decrease as the ethanol content rises, and subsequent operation with aqueous methanol only partly reverts this loss of performance. It seems that the difference in the oxidation rate of these alcohols may not be the only factor affecting fuel cell performance.

  3. The Impact of Foreign Direct Investment on the Export Performance: Empirical Evidence for Western Balkan Countries

    Dr.Sc. Nasir Selimi

    2016-07-01

    Full Text Available Recently there are many authors that have studied and analyzed the impact of foreign direct investments (FDI on the export performance. They have different opinions about the effect of foreign direct investments on the export performance. Some of them in their papers conclude that FDI have positive effect on the export performance and some not. There are also findings that FDI do not have any impact on the export performance. Of course for economic benefit of host country it is not important only the amount of FDI, but also their structure. To measure the effect of FDI on the export performance is not easy. Therefore, the main objective of this paper is to analyze empirically the foreign direct investments and exports performance during the period of 1996-2013 in Western Balkan countries. The paper also investigates for the fixed effects and individual heterogeneity across countries and years. Based on the panel regression techniques and Least Square Dummy Variable (LSDV regression method, FDI positively affect export performance in the sample countries in various model specifications. The results and conclusions of this paper we hope that will help everybody who are interested and studying this matter, especially the policy makers.  The last ones have the obligation to facilitate and promote the export if they award confirm that FDI contribute on developing their economy.

  4. Two stages of directed forgetting: Electrophysiological evidence from a short-term memory task.

    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. © 2016 Society for Psychophysiological Research.

  5. Mast cells are important modifiers of autoimmune disease: With so much evidence, why is there controversy?

    Melissa Ann Brown

    2012-06-01

    Full Text Available There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

  6. Direct Reprogramming of Adult Human Somatic Stem Cells Into Functional Neurons Using Sox2, Ascl1, and Neurog2

    Jessica Alves de Medeiros Araújo

    2018-06-01

    Full Text Available Reprogramming of somatic cells into induced pluripotent stem cells (iPS or directly into cells from a different lineage, including neurons, has revolutionized research in regenerative medicine in recent years. Mesenchymal stem cells are good candidates for lineage reprogramming and autologous transplantation, since they can be easily isolated from accessible sources in adult humans, such as bone marrow and dental tissues. Here, we demonstrate that expression of the transcription factors (TFs SRY (sex determining region Y-box 2 (Sox2, Mammalian achaete-scute homolog 1 (Ascl1, or Neurogenin 2 (Neurog2 is sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC into induced neurons (iNs. Furthermore, the combination of Sox2/Ascl1 or Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs showing electrical properties of mature neurons and establishing synaptic contacts with co-culture primary neurons. Finally, we show evidence supporting the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2 may induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs, suggesting that neuronal fate is determined by a combination of signals involving the TFs used for reprogramming but also the internal state of the converted cell. Altogether, the data presented here contribute to the advancement of techniques aiming at obtaining specific neuronal phenotypes from lineage-converted human somatic cells to treat neurological disorders.

  7. The role of massage in sports performance and rehabilitation: current evidence and future direction.

    Brummitt, Jason

    2008-02-01

    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. 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. 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. RESEARCH STUDIES PERTAINING TO THE FOLLOWING GENERAL CATEGORIES WERE IDENTIFIED AND REVIEWED: pre-event (physiological and psychological variables), sports performance, recovery, and rehabilitation. Despite the fact clinical research has been performed, a poor appreciation exists for the appropriate clinical use of sports massage. 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.

  8. Study on the micro direct ethanol fuel cell (Micro-DEFC) performance

    Saisirirat, Penyarat; Joommanee, Bordindech

    2018-01-01

    The direct ethanol fuel cell (DEFC) is selected for this research. DEFC uses ethanol in the fuel cell instead of the more toxic methanol. Ethanol is more attractive than methanol by many reasons. Ethanol is a hydrogen-rich liquid and it has a higher specific energy (8.0 kWh/kg) compared to that of methanol (6.1 kWh/kg). Ethanol can be obtained in great quantity from biomass through a fermentation process from renewable resources such as sugar cane, wheat, corn, and even straw. The use of ethanol would also overcome both the storage and infrastructure challenge of hydrogen for fuel cell applications. The experimental apparatus on the micro direct ethanol fuel cell for measuring the cell performance has been set for this research. The objective is to study the micro direct ethanol fuel cell performance for applying with the portable electronic devices. The cell performance is specified in the terms of cell voltage, cell current and power of the cell at room operating temperature and 1 atm for the pressure and also includes the ethanol fuel consumption. The effect of operating temperature change on the electrical production performance is also studied. The steady-state time for collecting each data value is about 5-10 minutes. The results show that with the increase of concentrations of ethanol by volume, the reactant concentration at the reaction sites increases so the electrochemical rate also increases but when it reaches the saturated point the performance gradually drops.

  9. Optical micromanipulation of active cells with minimal perturbations: direct and indirect pushing.

    Wang, Chenlu; Chowdhury, Sagar; Gupta, Satyandra K; Losert, Wolfgang

    2013-04-01

    The challenge to wide application of optical tweezers in biological micromanipulation is the photodamage caused by high-intensity laser exposure to the manipulated living systems. While direct exposure to infrared lasers is less likely to kill cells, it can affect cell behavior and signaling. Pushing cells with optically trapped objects has been introduced as a less invasive alternative, but the technique includes some exposure of the biological object to parts of the optical tweezer beam. To keep the cells farther away from the laser, we introduce an indirect pushing-based technique for noninvasive manipulation of sensitive cells. We compare how cells respond to three manipulation approaches: direct manipulation, pushing, and indirect pushing. We find that indirect manipulation techniques lessen the impact of manipulation on cell behavior. Cell survival increases, as does the ability of cells to maintain shape and wiggle. Our experiments also demonstrate that indirect pushing allows cell-cell contacts to be formed in a controllable way, while retaining the ability of cells to change shape and move.

  10. Biochemical and microscopic evidence for the internalization and degradation of heparin-containing mast cell granules by bovine endothelial cells

    Atkins, F.M.; Friedman, M.M.; Metcalfe, D.D.

    1985-01-01

    Incubation of [ 35 S]heparin-containing mast cell granules with cultured bovine endothelial cells was followed by the appearance of 35 S-granule-associated radioactivity within the endothelial cells and a decrease in radioactivity in the extracellular fluid. These changes occurred during the first 24 hours of incubation and suggested ingestion of the mast cell granules by the endothelial cells. Periodic electron microscopic examination of the monolayers confirmed this hypothesis by demonstrating apposition of the granules to the plasmalemma of endothelial cells, which was followed by the engulfment of the granules by cytoplasmic projections. Under light microscopic examination, mast cell granules within endothelial cells then appeared to undergo degradation. The degradation of [ 35 S]heparin in mast cell granules was demonstrated by a decrease in the amount of intracellular [ 35 S]heparin proteoglycan after 24 hours and the appearance of free [ 35 S]sulfate in the extracellular compartment. Intact endothelial cells were more efficient at degrading [ 35 S]heparin than were cell lysates or cell supernatants. These data provide evidence of the ability of endothelial cells to ingest mast cell granules and degrade native heparin that is presented as a part of the mast cell granule

  11. Effects of dissolved iron and chromium on the performance of direct methanol fuel cell

    Chen, Weimin; Xin, Qin; Sun, Gongquan; Yang, Shaohua; Zhou, Zhenhua; Mao, Qing; Sun, Pichang

    2007-01-01

    Effects of Fe 3+ and Cr 3+ ions on the performance of direct methanol fuel cell were investigated. The results show that the cell performance decreased remarkably when the concentration of Fe 3+ or Cr 3+ exceeded 1 x 10 -4 mol L -1 . Fe 3+ displayed a strong negative effect on the catalytic oxidation of methanol, while Cr 3+ affected the cell performance primarily by exchanging with protons of the membrane/ionomer and resulted in ionic conductivity losses. Complete recovery of the cell performance was not obtained after flushing the cell with deionized water

  12. Direct Cell-Cell Contact between Mesenchymal Stem Cells and Endothelial Progenitor Cells Induces a Pericyte-Like Phenotype In Vitro

    Markus Loibl

    2014-01-01

    Full Text Available Tissue engineering techniques for the regeneration of large bone defects require sufficient vascularisation of the applied constructs to ensure a sufficient supply of oxygen and nutrients. In our previous work, prevascularised 3D scaffolds have been successfully established by coculture of bone marrow derived stem cells (MSCs and endothelial progenitor cells (EPCs. We identified stabilising pericytes (PCs as part of newly formed capillary-like structures. In the present study, we report preliminary data on the interactions between MSCs and EPCs, leading to the differentiation of pericyte-like cells. MSCs and EPCs were seeded in transwell cultures, direct cocultures, and single cultures. Cells were cultured for 10 days in IMDM 10% FCS or IMDM 5% FCS 5% platelet lysate medium. Gene expression of PC markers, CD146, NG2, αSMA, and PDGFR-β, was analysed using RT-PCR at days 0, 3, 7, and 10. The upregulation of CD146, NG2, and αSMA in MSCs in direct coculture with EPCs advocates the MSCs’ differentiation towards a pericyte-like phenotype in vitro. These results suggest that pericyte-like cells derive from MSCs and that cell-cell contact with EPCs is an important factor for this differentiation process. These findings emphasise the concept of coculture strategies to promote angiogenesis for cell-based tissue engineered bone grafts.

  13. Aminopeptidase N is directly sorted to the apical domain in MDCK cells

    Wessels, H P; Hansen, Gert Helge; Fuhrer, C

    1990-01-01

    In different epithelial cell types, integral membrane proteins appear to follow different sorting pathways to the apical surface. In hepatocytes, several apical proteins were shown to be transported there indirectly via the basolateral membrane, whereas in MDCK cells a direct sorting pathway from...

  14. MONITORING REACTIONS IN ALKALINE DIRECT ETHANOL FUEL CELLS ASSEMBLED WITH NON-PT-CATALYST

    Gülzow, Erich; Beyer, Monique; Friedrich, K. Andreas; Pengel, Stefanie; Fischer, Peter; Bettermann, Hans

    2011-01-01

    This contribution shows how Raman spectroscopy can be used to pursue chemical reactions within fuel cells. For this, the oxidation of ethanol occurring in an alkaline direct ethanolic fuel cell was investigated. The analysis of a sequence of Raman spectra recorded during the reaction shows that ethanol was solely oxidized to acetate in a unique reaction.

  15. Challenges in Design of an Orientation free Micro Direct Methanol Fuel Cell (µDMFC)

    Omidvarnia, Farzaneh; Hansen, Hans Nørgaard; Hales, Jan Harry

    2014-01-01

    the challenges in design and manufacturing of a micro direct methanol fuel cell (μDMFC) as the power generator in hearing aid devices is investigated. Among the different challenges in design for μDMFC, the CO2 bubble management and orientation independency of the cell are addressed by proposing a spring loaded...

  16. Transport phenomena in alkaline direct ethanol fuel cells for sustainable energy production

    An, L.; Zhao, T. S.

    2017-02-01

    Alkaline direct ethanol fuel cells (DEFC), which convert the chemical energy stored in ethanol directly into electricity, are one of the most promising energy-conversion devices for portable, mobile and stationary power applications, primarily because this type of fuel cell runs on a carbon-neutral, sustainable fuel and the electrocatalytic and membrane materials that constitute the cell are relatively inexpensive. As a result, the alkaline DEFC technology has undergone a rapid progress over the last decade. This article provides a comprehensive review of transport phenomena of various species in this fuel cell system. The past investigations into how the design and structural parameters of membrane electrode assemblies and the operating parameters affect the fuel cell performance are discussed. In addition, future perspectives and challenges with regard to transport phenomena in this fuel cell system are also highlighted.

  17. Intraplate Crustal Deformation Within the Northern Sinai Microplate: Evidence from Paleomagnetic Directions and Mechanical Modeling

    Dembo, N.; Granot, R.; Hamiel, Y.

    2017-12-01

    The intraplate crustal deformation found in the northern part of the Sinai Microplate, located near the northern Dead Sea Fault plate boundary, is examined. Previous studies have suggested that distributed deformation in Lebanon is accommodated by regional uniform counterclockwise rigid block rotations. However, remanent magnetization directions observed near the Lebanese restraining bend are not entirely homogeneous suggesting that an unexplained and complex internal deformation pattern exists. In order to explain the variations in the amount of vertical-axis rotations we construct a mechanical model of the major active faults in the region that simulates the rotational deformation induced by motion along these faults. The rotational pattern calculated by the mechanical modeling predicts heterogeneous distribution of rotations around the faults. The combined rotation field that considers both the fault induced rotations and the already suggested regional block rotations stands in general agreement with the observed magnetization directions. Overall, the modeling results provide a more detailed and complete picture of the deformation pattern in this region and show that rotations induced by motion along the Dead Sea Fault act in parallel to rigid block rotations. Finally, the new modeling results unravel important insights as to the fashion in which crustal deformation is distributed within the northern part of the Sinai Microplate and propose an improved deformational mechanism that might be appropriate for other plate margins as well.

  18. Does Foreign Direct Investment Affect Green Growth? Evidence from China’s Experience

    Shujing Yue

    2016-02-01

    Full Text Available Foreign Direct Investment (FDI not only affects the economic growth but also affects the environmental protection of the host country. With China’s background of pursuing green growth, we need to consider the performance of FDI from the economic and environmental benefit aspects. On this basis, using slacks-based measure directional distance function (SBMDDF to build up green growth efficiency, economic efficiency and environmental efficiency indexes, empirical research on FDI in 104 Chinese cities from 2004 to 2011 has shown that: (1 Different cities have differences in their green growth efficiency. Shenzhen city is always efficient in green economic growth. (2 Overall, FDI is positive on Chinese cities’ green growth. (3 When the green growth efficiency is broken down into economic efficiency and environmental efficiency, FDI promotes China’s economic green growth through both environmental benefits and economic benefits. (4 The effect of FDI differs in different sectors. FDI in the emission-intensive sector promotes green efficiency mainly through the improvement of economic efficiency. FDI in the non-emission-intensive sector promotes economic efficiency, environmental efficiency and green efficiency.

  19. The Impact of Foreign Direct Investment (FDI on the Environment: Market Perspectives and Evidence from China

    Jiajia Zheng

    2017-03-01

    Full Text Available Foreign direct investment (FDI may have a positive effect on the level of pollution in host countries, as described by the pollution haven hypothesis (PHH. However, this kind of effect may depend on the economic conditions in host countries. In this study, we conduct research on the FDI’s effect on China’s CO2 emissions during the market-oriented reform. The results are as follows. Firstly, FDI directly promotes China’s CO2 emissions. Secondly, with market-oriented reform, this positive effect from FDI is lowering year by year, which indicates that the market-oriented reform could alleviate the positive effect of FDI on China’s CO2 emissions. Thirdly, as China’s market-oriented reform was implemented gradually from experimental zones to the whole country, regional market development is uneven, and as such so is FDI’s effect on local CO2 emissions. Provinces in the eastern area generally evidenced higher market development and lower CO2 emissions from FDI, while four provinces in west area evidenced both lower market development and higher CO2 emissions from FDI.

  20. Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

    Gonzalo Rosso

    2017-11-01

    Full Text Available Background/Aims: Migration of Schwann cells (SCs progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs are two central events during the development of the peripheral nervous system (PNS. How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

  1. Highly Durable Direct Methanol Fuel Cell with Double-Layered Catalyst Cathode

    Jing Liu

    2015-01-01

    Full Text Available Polymer electrolyte membrane (PEM is one of the key components in direct methanol fuel cells. However, the PEM usually gets attacked by reactive oxygen species during the operation period, resulting in the loss of membrane integrity and formation of defects. Herein, a double-layered catalyst cathode electrode consisting of Pt/CeO2-C as inner catalyst and Pt/C as outer catalyst is fabricated to extend the lifetime and minimize the performance loss of DMFC. Although the maximum power density of membrane electrode assembly (MEA with catalyst cathode is slightly lower than that of the traditional one, its durability is significantly improved. No obvious degradation is evident in the MEA with double-layered catalyst cathode within durability testing. These results indicated that Pt/CeO2-C as inner cathode catalyst layer greatly improved the stability of MEA. The significant reason for the improved stability of MEA is the ability of CeO2 to act as free-radical scavengers.

  2. Study of catalysis for solid oxide fuel cells and direct methanol fuel cells

    Jiang, Xirong

    Fuel cells offer the enticing promise of cleaner electricity with lower environmental impact than traditional energy conversion technologies. Driven by the interest in power sources for portable electronics, and distributed generation and automotive propulsion markets, active development efforts in the technologies of both solid oxide fuel cell (SOFC) and direct methanol fuel cell (DMFC) devices have achieved significant progress. However, current catalysts for fuel cells are either of low catalytic activity or extremely expensive, presenting a key barrier toward the widespread commercialization of fuel cell devices. In this thesis work, atomic layer deposition (ALD), a novel thin film deposition technique, was employed to apply catalytic Pt to SOFC, and investigate both Pt skin catalysts and Pt-Ru catalysts for methanol oxidation, a very important reaction for DMFC, to increase the activity and utilization levels of the catalysts while simultaneously reducing the catalyst loading. For SOFCs, we explored the use of ALD for the fabrication of electrode components, including an ultra-thin Pt film for use as the electrocatalyst, and a Pt mesh structure for a current collector for SOFCs, aiming for precise control over the catalyst loading and catalyst geometry, and enhancement in the current collect efficiency. We choose Pt since it has high chemical stability and excellent catalytic activity for the O2 reduction reaction and the H2 oxidation reaction even at low operating temperatures. Working SOFC fuel cells were fabricated with ALD-deposited Pt thin films as an electrode/catalyst layer. The measured fuel cell performance reveals that comparable peak power densities were achieved for ALD-deposited Pt anodes with only one-fifth of the Pt loading relative to a DC-sputtered counterpart. In addition to the continuous electrocatalyst layer, a micro-patterned Pt structure was developed via the technique of area selective ALD. By coating yttria-stabilized zirconia, a

  3. Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration.

    Somogyi, Kálmán; Rørth, Pernille

    2004-07-01

    Cells migrating through a tissue exert force via their cytoskeleton and are themselves subject to tension, but the effects of physical forces on cell behavior in vivo are poorly understood. Border cell migration during Drosophila oogenesis is a useful model for invasive cell movement. We report that this migration requires the activity of the transcriptional factor serum response factor (SRF) and its cofactor MAL-D and present evidence that nuclear accumulation of MAL-D is induced by cell stretching. Border cells that cannot migrate lack nuclear MAL-D but can accumulate it if they are pulled by other migrating cells. Like mammalian MAL, MAL-D also responds to activated Diaphanous, which affects actin dynamics. MAL-D/SRF activity is required to build a robust actin cytoskeleton in the migrating cells; mutant cells break apart when initiating migration. Thus, tension-induced MAL-D activity may provide a feedback mechanism for enhancing cytoskeletal strength during invasive migration.

  4. No evidence for the use of stem cell therapy for tendon disorders : a systematic review

    Pas, Haiko I M F L; Moen, Maarten H; Haisma, Hidde J; Winters, Marinus

    2017-01-01

    INTRODUCTION: Stem cells have emerged as a new treatment option for tendon disorders. We systematically reviewed the current evidence for stem cell therapy in tendon disorders. METHODS: Randomised and non-randomised controlled trials, cohort studies and case series with a minimum of 5 cases were

  5. A probabilistic approach for the interpretation of RNA profiles as cell type evidence

    de Zoete, J.; Curran, J.; Sjerps, M.

    2016-01-01

    DNA profiles can be used as evidence to distinguish between possible donors of a crime stain. In some cases, both the prosecution and the defence claim that the cell material was left by the suspect but they dispute which cell type was left behind. For example, in sexual offense cases the

  6. The direct health-care burden of valvular heart disease: evidence from US national survey data

    Moore M

    2016-10-01

    Full Text Available Matt Moore,1 Jie Chen,2 Peter J Mallow,3 John A Rizzo4 1Global Health Economic Strategy, Edwards Lifesciences Inc, Irvine, CA, 2Department of Health Services and Administration, University of Maryland, College Park, MD, 3Health Economics and Outcomes Research, CTI Clinical Trial & Consulting Services Inc, Cincinnati, OH, 4Department of Preventive Medicine and Economics, Stony Brook University, Stony Brook, NY, USA Purpose: This study quantified the overall effects of aortic valve disease (AVD and mitral valve disease (MVD by disease severity on direct health-care costs to insurers and patients.Materials and methods: Based on 1996–2011 data from the Medical Expenditure Panel Survey (MEPS, a large, nationally representative US database, multivariate analyses were performed to assess the relationship between AVD and MVD and direct annual health-care costs to insurers and patients, at individual and US-aggregate levels. Adults aged 18 years and over with diagnosis codes for AVD or MVD based on International Classification of Diseases (ninth revision diagnosis codes were identified. Subjects were further classified as symptomatic AVD, asymptomatic AVD, symptomatic MVD, and asymptomatic MVD. These classifications were determined with clinical assistance and based in part on data availability in the MEPS.Results: The MEPS database included 148 patients with AVD: 53 patients with symptomatic AVD, 95 patients with asymptomatic AVD, and 1,051 with MVD, including 315 patients with symptomatic MVD and 736 patients with asymptomatic MVD. Symptomatic AVD had the largest incremental effect on annual per patient health-care expenditure: $12,789 for symptomatic AVD, $10,816 for asymptomatic AVD, $5,163 for symptomatic MVD, and $1,755 for asymptomatic MVD. When aggregated to the US population, heart-valve disease accounted for an incremental annual cost of $23.4 billion. The largest aggregate annual costs were incurred by patients with symptomatic MVD ($7

  7. Hybrid direct carbon fuel cells and their reaction mechanisms - a review

    Deleebeeck, Lisa; Kammer Hansen, Kent

    2014-01-01

    with carbon capture and storage (CCS) due to the high purity of CO2 emitted in the exhaust gas. Direct carbon (or coal) fuel cells (DCFCs) are directly fed with solid carbon to the anode chamber. The fuel cell converts the carbon at the anode and the oxygen at the cathode into electricity, heat and reaction......As coal is expected to continue to dominate power generation demands worldwide, it is advisable to pursue the development of more efficient coal power generation technologies. Fuel cells show a much higher fuel utilization efficiency, emit fewer pollutants (NOx, SOx), and are more easily combined...

  8. Hybrid Direct Carbon Fuel Cell Performance with Anode Current Collector Material

    Deleebeeck, Lisa; Kammer Hansen, Kent

    2015-01-01

    collectors were studied: Au, Ni, Ag, and Pt. It was shown that the performance of the direct carbon fuel cell (DCFC) is dependent on the current collector materials, Ni and Pt giving the best performance, due to their catalytic activity. Gold is suggested to be the best material as an inert current collector......The influence of the current collector on the performance of a hybrid direct carbon fuel cell (HDCFC), consisting of solid oxide fuel cell (SOFC) with a molten carbonate-carbon slurry in contact with the anode, has been investigated using current-voltage curves. Four different anode current...

  9. Gelatin-based laser direct-write technique for the precise spatial patterning of cells.

    Schiele, Nathan R; Chrisey, Douglas B; Corr, David T

    2011-03-01

    Laser direct-writing provides a method to pattern living cells in vitro, to study various cell-cell interactions, and to build cellular constructs. However, the materials typically used may limit its long-term application. By utilizing gelatin coatings on the print ribbon and growth surface, we developed a new approach for laser cell printing that overcomes the limitations of Matrigel™. Gelatin is free of growth factors and extraneous matrix components that may interfere with cellular processes under investigation. Gelatin-based laser direct-write was able to successfully pattern human dermal fibroblasts with high post-transfer viability (91% ± 3%) and no observed double-strand DNA damage. As seen with atomic force microscopy, gelatin offers a unique benefit in that it is present temporarily to allow cell transfer, but melts and is removed with incubation to reveal the desired application-specific growth surface. This provides unobstructed cellular growth after printing. Monitoring cell location after transfer, we show that melting and removal of gelatin does not affect cellular placement; cells maintained registry within 5.6 ± 2.5 μm to the initial pattern. This study demonstrates the effectiveness of gelatin in laser direct-writing to create spatially precise cell patterns with the potential for applications in tissue engineering, stem cell, and cancer research.

  10. Brain insulin signaling and Alzheimer's disease: current evidence and future directions.

    Schiöth, Helgi B; Craft, Suzanne; Brooks, Samantha J; Frey, William H; Benedict, Christian

    2012-08-01

    Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.

  11. Direct evidence for human reliance on rainforest resources in late Pleistocene Sri Lanka.

    Roberts, Patrick; Perera, Nimal; Wedage, Oshan; Deraniyagala, Siran; Perera, Jude; Eregama, Saman; Gledhill, Andrew; Petraglia, Michael D; Lee-Thorp, Julia A

    2015-03-13

    Human occupation of tropical rainforest habitats is thought to be a mainly Holocene phenomenon. Although archaeological and paleoenvironmental data have hinted at pre-Holocene rainforest foraging, earlier human reliance on rainforest resources has not been shown directly. We applied stable carbon and oxygen isotope analysis to human and faunal tooth enamel from four late Pleistocene-to-Holocene archaeological sites in Sri Lanka. The results show that human foragers relied primarily on rainforest resources from at least ~20,000 years ago, with a distinct preference for semi-open rainforest and rain forest edges. Homo sapiens' relationship with the tropical rainforests of South Asia is therefore long-standing, a conclusion that indicates the time-depth of anthropogenic reliance and influence on these habitats. Copyright © 2015, American Association for the Advancement of Science.

  12. Masked form priming in writing words from pictures: evidence for direct retrieval of orthographic codes.

    Bonin, P; Fayol, M; Peereman, R

    1998-09-01

    Three experiments used the masked priming paradigm to investigate the role of orthographic and phonological information in written picture naming. In all the experiments, participants had to write the names of pictures as quickly as possible under three different priming conditions. Nonword primes could be: (1) phonologically and orthographically related to the picture name; (2) orthographically related as in (1) but phonologically related to a lesser degree than in (1); (3) orthographically and phonologically unrelated except for the first consonant (or consonant cluster). Orthographic priming effects were observed with a prime exposure duration of 34 ms (Experiments 1 and 2) and of 51 ms (Experiment 3). In none of the experiments, did homophony between primes and picture names yield an additional advantage. Taken together, these findings support the view of the direct retrieval of orthographic information through lexical access in written picture naming, and thus argue against the traditional view that the retrieval of orthographic codes of obligatorily mediated by phonology.

  13. Determinants Of Foreign Direct Investment In Mauritius Evidence From Time Series Data

    Medha Kisto

    2017-08-01

    Full Text Available Over the last two decades Foreign Direct Investment FDI claimed an impressive economic record as it enables economy to transit from an agrarian to knowledge based economy. This paper focuses on the determinants and impact of FDI in Mauritius using annual time series data from 1975 through 2015. The Vector Error Correction Model VECM analysis reveals that macroeconomic variables namely inflation rates and exchange rate are among the major and important factor that affect FDI in Mauritius over this period of time. Exchange rate exhibited negative significant influence on FDI while interest rate affects FDI positively. The study therefore recommends that government should continue to diversify the export and tourism markets ensure stable macroeconomic policies implement reforms on doing business increase its expenditure in the area of infrastructural development and redirect FDI in productive sector of the economy as ways to accelerate the growth of Mauritian economy.

  14. Foreign direct investment, institutional development, and environmental externalities: evidence from China.

    Wang, Danny T; Chen, Wendy Y

    2014-03-15

    The question of how foreign direct investment (FDI) affects a host country's natural environment has generated much debate but little consensus. Building on an institution-based theory, this article examines how the institutional development of a host setting affects the degree of FDI-related environmental externalities in China (specifically, industrial sulfur dioxide emissions). With a panel data set of 287 Chinese cities, over the period 2002-2009, this study reveals that FDI in general induces negative environmental externalities. Investments from OECD countries increase sulfur dioxide emissions, whereas FDI from Hong Kong, Macau, and Taiwan shows no significant effect. Institutional development reduces the impacts of FDI across the board. By focusing on the moderating role of institutions, this study sheds new light on the long-debated relationships among FDI, institutions, and the environments of the host countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Analysis of antigen-specific B-cell memory directly ex vivo.

    McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

    2004-01-01

    Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

  16. Is Russia successful in attracting foreign direct investment? Evidence based on gravity model estimation

    Mariev Oleg

    2016-09-01

    Full Text Available The aim of this paper is twofold. First, it is to answer the question of whether Russia is successful in attracting foreign direct investment (FDI. Second, it is to identify partner countries that “overinvest” and “underinvest” in the Russian economy. We do this by calculating potential FDI inflows to Russia and comparing them with actual values. This research is associated with the empirical estimation of factors explaining FDI flows between countries. The methodological foundation used for the research is the gravity model of foreign direct investment. In discussing the pros and cons of different econometric methods of the estimation gravity equation, we conclude that the Poisson pseudo maximum likelihood method with instrumental variables (IV PPML is one of the best options in our case. Using a database covering about 70% of FDI flows for the period of 2001-2011, we discover the following factors that explain the variance of bilateral FDI flows in the world economy: GDP value of investing country, GDP value of recipient country, distance between countries, remoteness of investor country, remoteness of recipient country, level of institutions development in host country, wage level in host country, membership of two countries in a regional economic union, common official language, common border and colonial relationships between countries in the past. The potential values of FDI inflows are calculated using coefficients of regressors from the econometric model. We discover that the Russian economy performs very well in attracting FDI: the actual FDI inflows exceed potential values by 1.72 times. Large developed countries (France, Germany, UK, Italy overinvest in the Russian economy, while smaller and less developed countries (Czech Republic, Belarus, Denmark, Ukraine underinvest in Russia. Countries of Southeast Asia (China, South Korea, Japan also underinvest in the Russian economy.

  17. Direct Experimental Evidence of Back-Surface Acceleration from Laser-Irradiated Foils

    Allen, M; Patel, P; Mackinnon, A; Price, D; Wilks, S; Morse, E

    2004-01-01

    Au foils were irradiated with a 100-TW, 100-fs laser at intensities greater than 10 20 W/cm 2 producing proton beams with a total yield of ∼ 10 11 and maximum proton energy of > 9 MeV. Removing contamination from the back surface of Au foils with an Ar-ion sputter gun reduced the total yield of accelerated protons to less than 1% of the yield observed without removing contamination. Removing contamination the front surface (laser-interaction side) of the target had no observable effect on the proton beam. We present a one-dimensional particle-in-cell simulation that models the experiment. Both experimental and simulation results are consistent with the back-surface acceleration mechanism described in the text

  18. Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research

    Rafael N. Ruggiero

    2017-06-01

    Full Text Available Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC or ameliorate (e.g., cannabidiol, CBD schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB1 and TRPV1 agonist on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.

  19. Electrophysiological evidence for flexible goal-directed cue processing during episodic retrieval.

    Herron, Jane E; Evans, Lisa H; Wilding, Edward L

    2016-05-15

    A widely held assumption is that memory retrieval is aided by cognitive control processes that are engaged flexibly in service of memory retrieval and memory decisions. While there is some empirical support for this view, a notable exception is the absence of evidence for the flexible use of retrieval control in functional neuroimaging experiments requiring frequent switches between tasks with different cognitive demands. This absence is troublesome in so far as frequent switches between tasks mimic some of the challenges that are typically placed on memory outside the laboratory. In this experiment we instructed participants to alternate frequently between three episodic memory tasks requiring item recognition or retrieval of one of two different kinds of contextual information encoded in a prior study phase (screen location or encoding task). Event-related potentials (ERPs) elicited by unstudied items in the two tasks requiring retrieval of study context were reliably different, demonstrating for the first time that ERPs index task-specific processing of retrieval cues when retrieval goals change frequently. The inclusion of the item recognition task was a novel and important addition in this study, because only the ERPs elicited by unstudied items in one of the two context conditions diverged from those in the item recognition condition. This outcome constrains functional interpretations of the differences that emerged between the two context conditions and emphasises the utility of this baseline in functional imaging studies of retrieval processing operations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Direct evidence of Rickettsia typhi infection in Rhipicephalus sanguineus ticks and their canine hosts

    Karla Dzul-Rosado

    2017-06-01

    Full Text Available Murine typhus is a rickettsiosis caused by Rickettsia typhi, whose transmission is carried out by rat fleas in urban settlements as classically known, but it also has been related to cat fleas in a sub-urban alternative cycle that has been suggested by recent reports. These studies remarks that in addition to rats, other animals like cats, opossums and dogs could be implied in the transmission of Rickettsia typhi as infected fleas obtained from serologically positive animals have been detected in samples from endemic areas. In Mexico, the higher number of murine typhus cases have been detected in the Yucatan peninsula, which includes a great southeastern region of Mexico that shows ecologic characteristics similar to the sub-urban alternative cycle recently described in Texas and California at the United States. To find out which are the particular ecologic characteristics of murine typhus transmission in this region, we analyzed blood and Rhipicephalus sanguineus ticks obtained from domestic dogs by molecular approaches, demonstrating that both samples were infected by Rickettsia typhi. Following this, we obtained isolates that were analyzed by genetic sequencing to corroborate this infection in 100% of the analyzed samples. This evidence suggests for the first time that ticks and dogs could be actively participating in the transmission of murine typhus, in a role that requires further studies for its precise description.

  1. Trace element similarity groups in north Florida Spanish moss: evidence for direct uptake of aerosol particles

    Sheline, J.; Akselsson, R.; Winchester, J.W.

    1976-02-20

    The elemental composition of 10 samples of Spanish moss Tillandsia usneoides L. collected mainly in forested areas near Tallahassee, Florida, has been compared to the composition of the ambient aerosol particle background in the forest measured as a function of particle size. For forest samples, moss composition is similar to the composition of aerosol particles greater than about 0.5-..mu..m diameter for the elements S, Cl, Ti, V, Fe, Ni, Zn, Br, Pb, and possibly Cu. Elements relatively enriched in the moss fall into two groups, K, Rb, Zr and Ca, Sr, Mn, based on detailed association patterns. No evidence is found for an enrichment, relative to the ambient aerosol, of pollution-derived elements Pb, Br, V, and Ni, although those elements are found at higher concentrations in moss samples from locations nearer roadways or oil-fired power plants. The moss appears to have potential value as an indicator of time average aerosol composition for particles of greater than or equal to 0.5 ..mu..m, except for the enriched elements, which may have longer biological retention times. (auth)

  2. Direct evidence of spin frustration in the fcc antiferromagnet NiS sub 2

    Matsuura, M; Endoh, Y; Hirota, K; Yamada, K

    2002-01-01

    NiS sub 2 is a well-known Mott insulator with anomalous antiferromagnetic long-range order of coexistent type I (Q sub M =(1,0,0), T sub N sub 1 =40 K) and type II (Q sub M =(1/2,1/2,1/2), T sub N sub 2 =30 K). Extensive neutron-scattering measurements reveal that magnetism in NiS sub 2 is governed by geometrical spin frustration, resulting in magnetic diffuse scattering extending along the fcc zone boundary. Although the diffuse scattering exists at temperatures as high as 250 K (6T sub N sub 1), it disappears rapidly below T sub N sub 2 , associated with minor crystal distortion. We observed a clear energy gap in addition to the low-energy spin-wave excitation at significantly below 30 K, and obtain evidence that degeneracy due to the coexistence of the two types of antiferromagnetism is relieved in the ground state via the reduction in symmetry due to distortion. (orig.)

  3. Will a mAb-Based Immunotherapy Directed against Cancer Stem Cells Be Feasible?

    Silvia Santamaria

    2017-11-01

    Full Text Available The cancer stem cell (CSC hypothesis suggests that within a tumor, there is a small subpopulation of cells with stem cell properties responsible for tumor maintenance and metastasis generation. This hypothesis also implies that new antitumor drugs, rather than targeting the bulk of the tumor mass, would be more effective if they directly targeted the CSC subpopulation. The CSCs from several types of tumors have been identified with mAbs recognizing surface antigens in these cells; however, antigens specifically or exclusively expressed in the CSC population have not yet been identified. Thus, questioning the possibility of using therapeutic antibodies directed against the CSCs. Here, we review the possibilities of using antibodies directly targeting the CSCs as therapeutic agents in the form of naked antibodies, antibodies conjugated to nanoparticles, or antibody cocktails.

  4. The Degradation Interface of Magnesium Based Alloys in Direct Contact with Human Primary Osteoblast Cells.

    Nezha Ahmad Agha

    Full Text Available Magnesium alloys have been identified as a new generation material of orthopaedic implants. In vitro setups mimicking physiological conditions are promising for material / degradation analysis prior to in vivo studies however the direct influence of cell on the degradation mechanism has never been investigated. For the first time, the direct, active, influence of human primary osteoblasts on magnesium-based materials (pure magnesium, Mg-2Ag and Mg-10Gd alloys is studied for up to 14 days. Several parameters such as composition of the degradation interface (directly beneath the cells are analysed with a scanning electron microscope equipped with energy dispersive X-ray and focused ion beam. Furthermore, influence of the materials on cell metabolism is examined via different parameters like active mineralisation process. The results are highlighting the influences of the selected alloying element on the initial cells metabolic activity.

  5. The Degradation Interface of Magnesium Based Alloys in Direct Contact with Human Primary Osteoblast Cells.

    Ahmad Agha, Nezha; Willumeit-Römer, Regine; Laipple, Daniel; Luthringer, Bérengère; Feyerabend, Frank

    2016-01-01

    Magnesium alloys have been identified as a new generation material of orthopaedic implants. In vitro setups mimicking physiological conditions are promising for material / degradation analysis prior to in vivo studies however the direct influence of cell on the degradation mechanism has never been investigated. For the first time, the direct, active, influence of human primary osteoblasts on magnesium-based materials (pure magnesium, Mg-2Ag and Mg-10Gd alloys) is studied for up to 14 days. Several parameters such as composition of the degradation interface (directly beneath the cells) are analysed with a scanning electron microscope equipped with energy dispersive X-ray and focused ion beam. Furthermore, influence of the materials on cell metabolism is examined via different parameters like active mineralisation process. The results are highlighting the influences of the selected alloying element on the initial cells metabolic activity.

  6. Evidence for Differential Glycosylation of Trophoblast Cell Types*

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E.; Longtine, Mark S.; Schust, Danny J.; Haslam, Stuart M.; Blois, Sandra M.; Dell, Anne; Clark, Gary F.

    2016-01-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3–4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2–3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2–3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. PMID:26929217

  7. Evidence for Differential Glycosylation of Trophoblast Cell Types.

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E; Longtine, Mark S; Schust, Danny J; Haslam, Stuart M; Blois, Sandra M; Dell, Anne; Clark, Gary F

    2016-06-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3-4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2-3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2-3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Future directions in psychological assessment: combining evidence-based medicine innovations with psychology's historical strengths to enhance utility.

    Youngstrom, Eric A

    2013-01-01

    Assessment has been a historical strength of psychology, with sophisticated traditions of measurement, psychometrics, and theoretical underpinnings. However, training, reimbursement, and utilization of psychological assessment have been eroded in many settings. Evidence-based medicine (EBM) offers a different perspective on evaluation that complements traditional strengths of psychological assessment. EBM ties assessment directly to clinical decision making about the individual, uses simplified Bayesian methods explicitly to integrate assessment data, and solicits patient preferences as part of the decision-making process. Combining the EBM perspective with psychological assessment creates a hybrid approach that is more client centered, and it defines a set of applied research topics that are highly clinically relevant. This article offers a sequence of a dozen facets of the revised assessment process, along with examples of corollary research studies. An eclectic integration of EBM and evidence-based assessment generates a powerful hybrid that is likely to have broad applicability within clinical psychology and enhance the utility of psychological assessments.

  9. Measurement of direct CP violation in the NA48 experiment; Mise en evidence de la violation directe de CP par l'experience NA48

    Formica, A

    2001-10-01

    The 2 first chapters of this thesis are dedicated to the theoretical and experimental aspects of CP violation. The NA48 experiment is a third generation experiment like KTeV, NA48 has been designed to collect data concerning the simultaneous detection of the 4 decay modes: K{sub L,S} {yields} {pi}{pi} and to provide the measurement of the parameter of direct CP violation with an uncertainty nearing 2*10{sup -4}. The third chapter describes the experimental equipment of NA48 in CERN: the production of K{sub L} and K{sub S} beams, the tagging system, the detection system for K {yields} {pi}{sup +}{pi}{sup -}, the detection system for K {yields} {pi}{sup 0}{pi}{sup 0}, the data acquisition system, and the trigger system. Chapter 4 is dedicated to the selection and identification of events. Chapter 5 deals with specific problems concerning the detection of {pi}{sup +}{pi}{sup -}, it means: the dead time in the triggering system, the overflow of the chamber reading system and the inefficiency of shift chambers. Chapter 6 lists the different corrections and systematic errors concerning the double ratio R, and gives the following result: Re({epsilon}'/{epsilon}=(14.4{+-}2.6)*10{sup -4}) which is by itself, for the first time, an evidence of direct violation. (A.C.)

  10. Recent advances on Zeolite modification for direct alcohol fuel cells (DAFCs)

    Makertihartha, I. G. B. N.; Zunita, M.; Rizki, Z.; Dharmawijaya, P. T.

    2017-03-01

    The increase of energy demand and global warming issues has driven studies of alternative energy sources. The polymer electrolyte membrane fuel cell (PEMFC) can be an alternative energy source by (partially) replacing the use of fossil fuel which is in line with the green technology concept. However, the usage of hydrogen as a fuel has several disadvantages mainly transportation and storage related to its safety aspects. Recently, alcohol has gained attention as an energy source for fuel cell application, namely direct alcohol fuel cell (DAFC). Among alcohols, high-mass energy density methanol and ethanol are widely used as direct methanol fuel cell (DMFC) and direct ethanol fuel cell (DEFC), respectively. Currently, the performance of DMFC is still rudimentary. Furthermore, the use of ethanol gives some additional privileges such as non-toxic property, renewable, ease of production in great quantity by the fermentation of sugar-containing raw materials. Direct alcohol fuel cell (DAFC) still has weakness in the low proton conductivity and high alcohol crossover. Therefore, to increase the performance of DAFC, modification using zeolite has been performed to improve proton conductivity and decrease alcohol crossover. Zeolite also has high thermal resistance properties, thereby increasing DAFC performance. This paper will discuss briefly about modification of catalyst and membrane for DAFC using zeolite. Zeolite modification effect on fuel cell performance especially proton conductivity and alcohol crossover will be presented in detail.

  11. The Use of Evidence in Public Debates in the Media: The Case of Swiss Direct-Democratic Campaigns in the Health Policy Sector

    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…

  12. An engineered cell-imprinted substrate directs osteogenic differentiation in stem cells

    Kamguyan, Khorshid; Katbab, Ali Asghar; Mahmoudi, Morteza

    2018-01-01

    A cell-imprinted poly(dimethylsiloxane)/hydroxyapatite nanocomposite substrate was fabricated to engage topographical, mechanical, and chemical signals to stimulate and boost stem cell osteogenic differentiation. The physicochemical properties of the fabricated substrates, with nanoscale resolution...

  13. Directed Secretion by Bone Cells of a Factor that Attracts Breast Cancer Cells

    Gay, Carol

    2001-01-01

    The hFOB osteoblast cell line was cultured in both undifferentiated and differentiated states and tested for the capacity of the cell layers to occlude fluorescent-tagged dextrans of 4-, 20- and 40 kD molecular weight...

  14. The morphological and molecular changes of brain cells exposed to direct current electric field stimulation.

    Pelletier, Simon J; Lagacé, Marie; St-Amour, Isabelle; Arsenault, Dany; Cisbani, Giulia; Chabrat, Audrey; Fecteau, Shirley; Lévesque, Martin; Cicchetti, Francesca

    2014-12-07

    The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  15. Evidence for a stepwise program of extrathymic T cell development within the human tonsil

    McClory, Susan; Hughes, Tiffany; Freud, Aharon G.; Briercheck, Edward L.; Martin, Chelsea; Trimboli, Anthony J.; Yu, Jianhua; Zhang, Xiaoli; Leone, Gustavo; Nuovo, Gerard; Caligiuri, Michael A.

    2012-01-01

    The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34+CD38dimLin– cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34+CD38brightLin– cells; (c) CD34+CD1a+CD11c– cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34–CD1a+CD3–CD11c– cells, which resemble CD4+CD8+ double-positive T cells in the thymus; and (e) CD34–CD1a+CD3+CD11c– cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT+ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre–T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development. PMID:22378041

  16. Direct evidence of advantage of using nanosized zeolite Beta for ISFET-based biosensor construction

    Soy, Esin; Galioglu, Sezin; Soldatkin, Oleksandr O.; Dzyadevych, Sergei V.; Warzywoda, Juliusz; Sacco, Albert; Akata, Burcu

    2013-01-01

    Analytical characteristics of urease- and butyrylcholinesterase (BuChE)- based ion sensitive field-effect transistor (ISFET) biosensors were investigated by the incorporation of zeolite Beta nanoparticles with varying Si/Al ratios. The results obtained by the zeolite-modified ISFET transducers suggested that the Si/Al ratio strongly influenced the biosensor performances due to the electrostatic interactions among enzyme, substrate, and zeolite surface as well as the nature of the enzymatic reaction. Using relatively small nanoparticles (62.7 ± 10, 76.2 ± 10, and 77.1 ± 10 nm) rather than larger particles, that are widely used in the literature, allow us to produce more homogenous products which will give more control over the quantity of materials used on the electrode surface and ability to change solely Si/Al ratio without changing other parameters such as particle size, pore volume, and surface area. This should enable the investigation of the individual effect of changing acidic and electronic nature of this material on the biosensor characteristics. According to our results, high biosensor sensitivity is evident on nanosize and submicron size particles, with the former resulting in higher performance. The sensitivity of biosensors modified by zeolite particles is higher than that to the protein for both types of biosensors. Most significantly, our results show that the performance of constructed ISFET-type biosensors strongly depends on Si/Al ratio of employed zeolite Beta nanoparticles as well as the type of enzymatic reaction employed. All fabricated biosensors demonstrated high signal reproducibility and stability for both BuChE and urease.

  17. Digital mental health and intellectual disabilities: state of the evidence and future directions.

    Sheehan, Rory; Hassiotis, Angela

    2017-11-01

    The use of digital technologies in the management of mental illness, and more generally in the promotion of well-being and mental health, has received much recent attention and is a focus of current health policy. We conducted a narrative review to explore the opportunities and risks of digital technologies in mental healthcare specifically for people with intellectual disability, a sometimes marginalised and socially excluded group. The scope of digital mental health is vast and the promise of cheaper and more effective interventions delivered digitally is attractive. People with intellectual disability experience high rates of mental illness and could benefit from the development of novel therapies, yet seem to have been relatively neglected in the discourse around digital mental health and are often excluded from the development and implementation of new interventions. People with intellectual disability encounter several barriers to fully embracing digital technology, which may be overcome with appropriate support and adaptations. A small, but growing, literature attests to the value of incorporating digital technologies into the lives of people with intellectual disability, not only for promoting health but also for enhancing educational, vocational and leisure opportunities. Clearly further evidence is needed to establish the safety and clinical efficacy of digital mental health interventions for people with and without intellectual disability. A digital inclusion strategy that explicitly addresses the needs of people with intellectual disability would ensure that all can share the benefits of the digital world. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. First direct evidence of chalcolithic footwear from the near eastern highlands.

    Pinhasi, Ron

    2010-01-01

    In 2008, a well preserved and complete shoe was recovered at the base of a Chalcolithic pit in the cave of Areni-1, Armenia. Here, we discuss the chronology of this find, its archaeological context and its relevance to the study of the evolution of footwear. Two leather samples and one grass sample from the shoe were dated at the Oxford Radiocarbon Accelerator Unit (ORAU). A third leather sample was dated at the University of California-Irvine Accelerator Mass Spectrometry Facility (UCIAMS). The R_Combine function for the three leather samples provides a date range of 3627-3377 Cal BC (95.4% confidence interval) and the calibrated range for the straw is contemporaneous (3627-3377 Cal BC). The shoe was stuffed with loose, unfastened grass (Poaceae) without clear orientation which was more than likely used to maintain the shape of the shoe and\\/or prepare it for storage. The shoe is 24.5 cm long (European size 37), 7.6 to 10 cm wide, and was made from a single piece of leather that wrapped around the foot. It was worn and shaped to the wearer\\'s right foot, particularly around the heel and hallux where the highest pressure is exerted in normal gait. The Chalcolithic shoe provides solid evidence for the use of footwear among Old World populations at least since the Chalcolithic. Other 4th millennium discoveries of shoes (Italian and Swiss Alps), and sandals (Southern Israel) indicate that more than one type of footwear existed during the 4th millennium BC, and that we should expect to discover more regional variations in the manufacturing and style of shoes where preservation conditions permit.

  19. Thermal radiation characteristics and direct evidence of tungsten cooling on the way to nanostructure formation on its surface

    Takamura, S., E-mail: takamura@aitech.ac.jp [Faculty of Engineering, Aichi Institute of Technology, Yakusa-cho, Toyota 470-0392 (Japan); Miyamoto, T. [Faculty of Engineering, Aichi Institute of Technology, Yakusa-cho, Toyota 470-0392 (Japan); Ohno, N. [Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)

    2013-07-15

    The physical properties of tungsten with nanostructure on its surface are investigated focusing on the thermal radiation and cooling characteristics. First, direct evidence of substantial W surface cooling has been clearly shown with use of a very thin thermocouple inserted into W target, which solves an uncertainty associated with a radiation thermometer. Second, the above measurements of W surface temperature make it possible to estimate quantitatively the total emissivity from which we may evaluate the radiative power through the Stefan–Boltzmann equation, which is very important for mitigation evaluation of a serious plasma heat load to the plasma-facing component.

  20. Thermal radiation characteristics and direct evidence of tungsten cooling on the way to nanostructure formation on its surface

    Takamura, S.; Miyamoto, T.; Ohno, N.

    2013-01-01

    The physical properties of tungsten with nanostructure on its surface are investigated focusing on the thermal radiation and cooling characteristics. First, direct evidence of substantial W surface cooling has been clearly shown with use of a very thin thermocouple inserted into W target, which solves an uncertainty associated with a radiation thermometer. Second, the above measurements of W surface temperature make it possible to estimate quantitatively the total emissivity from which we may evaluate the radiative power through the Stefan–Boltzmann equation, which is very important for mitigation evaluation of a serious plasma heat load to the plasma-facing component

  1. Is Obesity Stigma Based on Perceptions of Appearance or Character? Theory, Evidence, and Directions for Further Study

    Florian van Leeuwen

    2015-08-01

    Full Text Available Theoretical approaches to stigmatization have highlighted distinct psychological mechanisms underlying distinct instances of stigmatization. Some stigmas are based on inferences of substandard psychological character (e.g., individuals deemed untrustworthy, whereas others are based on perceptions of substandard physical appearance (e.g., individuals with physical deformities. These inferences and perceptions are associated with specific cognitive and motivational processes, which have implications for understanding specific instances of stigmatization. Recent theoretical approaches and empirical findings suggest that obesity stigma involves both inferences of substandard psychological character and perceptions of substandard physical appearance. We provide a review of the relevant evidence and discuss directions for future research.

  2. A Review of e-Learning in Canada: A Rough Sketch of the Evidence, Gaps and Promising Directions

    Philip C Abrami; Robert Bernard; Anne Wade; Richard F. Schmid; Eugene Borokhovski; Rana Tamin; Michael Surkes; Gretchen Lowerison; Dai Zhang; Iolie Nicolaidou; Sherry Newman; Lori Wozney; Anna Peretiatkowicz

    2008-01-01

    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. We 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 our database, of which we reviewed 1,146, including all the Canadian primary research and all scholarly reviews of the literature. In total, there were 726 documents in...

  3. Dopaminergic modulation of positive expectations for goal-directed action: evidence from Parkinson’s disease

    Noham eWolpe

    2015-10-01

    Full Text Available Parkinson’s disease (PD impairs the control of movement and cognition, including the planning of action and its consequences. This provides the opportunity to study the dopaminergic influences on the perception and awareness of action. Here we examined the perception of the outcome of a goal-directed action made by medicated patients with PD. A visuomotor task probed the integration of sensorimotor signals with the positive expectations of outcomes (Self priors, which in healthy adults bias perception towards success in proportion to trait optimism. We tested the hypotheses that (i the priors on the perception of the consequences of one’s own actions differ between patients and age- and sex-matched controls, and (ii that these priors are modulated by the levodopa dose equivalent in patients. There was no overall difference between patients and controls in the perceptual priors used. However, the precision of patient priors was inversely related to their levodopa dose equivalent. Patients with high levodopa dose equivalent showed more accurate priors, representing predictions that were closer to the true distribution of performance. Such accuracy has previously been demonstrated when observing the actions of others, suggesting abnormal awareness of action in these patients. These results confirm a link between dopamine and the positive expectation of the outcome of one’s own actions, and may have implications for the management of PD.

  4. Do coverage mandates affect direct-to-consumer advertising for pharmaceuticals? Evidence from parity laws.

    Nathenson, Robert; Richards, Michael R

    2018-01-29

    Direct-to-consumer advertising (DTCA) for prescription drugs is a relatively unique feature of the US health care system and a source of tens of billions of dollars in annual spending. It has also garnered the attention of researchers and policymakers interested in its implications for firm and consumer behavior. However, few economic studies have explored the DTCA response to public policies, especially those mandating coverage of these products. We use detailed advertising expenditure data to assess if pharmaceutical firms increase their marketing efforts after the implementation of relevant state and federal health insurance laws. We focus on mental health parity statutes and related drug therapies-a potentially ripe setting for inducing stronger consumer demand. We find no clear indication that firms expect greater value from DTCA after these regulatory changes. DTCA appears driven by other considerations (e.g., product debut); however, it remains a possibility that firms respond to these laws through other, unobserved channels (e.g., provider detailing).

  5. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  6. Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.

    Lucas, Bronwyn A; Lavi, Eitan; Shiue, Lily; Cho, Hana; Katzman, Sol; Miyoshi, Keita; Siomi, Mikiko C; Carmel, Liran; Ares, Manuel; Maquat, Lynne E

    2018-01-30

    Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs. To explore this possibility, we searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE and each regulated by SMD, by measuring changes in mRNA abundance after individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'-UTR SINEs that independently function in SMD control of myoblast metabolism. Expanding to other species, we demonstrated that SINE-directed SMD likely emerged in both primate and rodent lineages >20-25 million years ago. Our work reveals a mechanism for the convergent evolution of posttranscriptional gene regulatory networks in mammals by species-specific SINE transposition and SMD.

  7. Direct lexical control of eye movements in reading: Evidence from a survival analysis of fixation durations

    Reingold, Eyal M.; Reichle, Erik D.; Glaholt, Mackenzie G.; Sheridan, Heather

    2013-01-01

    Participants’ eye movements were monitored in an experiment that manipulated the frequency of target words (high vs. low) as well as their availability for parafoveal processing during fixations on the pre-target word (valid vs. invalid preview). The influence of the word-frequency by preview validity manipulation on the distributions of first fixation duration was examined by using ex-Gaussian fitting as well as a novel survival analysis technique which provided precise estimates of the timing of the first discernible influence of word frequency on first fixation duration. Using this technique, we found a significant influence of word frequency on fixation duration in normal reading (valid preview) as early as 145 ms from the start of fixation. We also demonstrated an equally rapid non-lexical influence on first fixation duration as a function of initial landing position (location) on target words. The time-course of frequency effects, but not location effects was strongly influenced by preview validity, demonstrating the crucial role of parafoveal processing in enabling direct lexical control of reading fixation times. Implications for models of eye-movement control are discussed. PMID:22542804

  8. Emotion and goal-directed behavior: ERP evidence on cognitive and emotional conflict

    Kanske, Philipp; Obermeier, Christian; Schröger, Erich; Kotz, Sonja A.

    2015-01-01

    Cognitive control supports goal-directed behavior by resolving conflict among opposing action tendencies. Emotion can trigger cognitive control processes, thus speeding up conflict processing when the target dimension of stimuli is emotional. However, it is unclear what role emotionality of the target dimension plays in the processing of emotional conflict (e.g. in irony). In two EEG experiments, we compared the influence of emotional valence of the target (emotional, neutral) in cognitive and emotional conflict processing. To maximally approximate real-life communication, we used audiovisual stimuli. Participants either categorized spoken vowels (cognitive conflict) or their emotional valence (emotional conflict), while visual information was congruent or incongruent. Emotional target dimension facilitated both cognitive and emotional conflict processing, as shown in a reduced reaction time conflict effect. In contrast, the N100 in the event-related potentials showed a conflict-specific reversal: the conflict effect was larger for emotional compared with neutral trials in cognitive conflict and smaller in emotional conflict. Additionally, domain-general conflict effects were observed in the P200 and N200 responses. The current findings confirm that emotions have a strong influence on cognitive and emotional conflict processing. They also highlight the complexity and heterogeneity of the interaction of emotion with different types of conflict. PMID:25925271

  9. Direct evidence for radiative charge transfer after inner-shell excitation and ionization of large clusters

    Hans, Andreas; Stumpf, Vasili; Holzapfel, Xaver; Wiegandt, Florian; Schmidt, Philipp; Ozga, Christian; Reiß, Philipp; Ben Ltaief, Ltaief; Küstner-Wetekam, Catmarna; Jahnke, Till; Ehresmann, Arno; Demekhin, Philipp V.; Gokhberg, Kirill; Knie, André

    2018-01-01

    We directly observe radiative charge transfer (RCT) in Ne clusters by dispersed vacuum-ultraviolet photon detection. The doubly ionized Ne2+-{{{N}}{{e}}}n-1 initial states of RCT are populated after resonant 1s-3p photoexcitation or 1s photoionization of Ne n clusters with ≈ 2800. These states relax further producing Ne+-Ne+-{{{N}}{{e}}}n-2 final states, and the RCT photon is emitted. Ab initio calculations assign the observed RCT signal to the{}{{{N}}{{e}}}2+(2{{{p}}}-2{[}1{{D}}]){--}{{{N}}{{e}}}n-1 initial state, while transitions from other possible initial states are proposed to be quenched by competing relaxation processes. The present results are in agreement with the commonly discussed scenario, where the doubly ionized atom in a noble gas cluster forms a dimer which dissipates its vibrational energy on a picosecond timescale. Our study complements the picture of the RCT process in weakly bound clusters, providing information which is inaccessible by charged particle detection techniques.

  10. Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation.

    Yoo, Jejoong; Kim, Hajin; Aksimentiev, Aleksei; Ha, Taekjip

    2016-03-22

    Although proteins mediate highly ordered DNA organization in vivo, theoretical studies suggest that homologous DNA duplexes can preferentially associate with one another even in the absence of proteins. Here we combine molecular dynamics simulations with single-molecule fluorescence resonance energy transfer experiments to examine the interactions between duplex DNA in the presence of spermine, a biological polycation. We find that AT-rich DNA duplexes associate more strongly than GC-rich duplexes, regardless of the sequence homology. Methyl groups of thymine acts as a steric block, relocating spermine from major grooves to interhelical regions, thereby increasing DNA-DNA attraction. Indeed, methylation of cytosines makes attraction between GC-rich DNA as strong as that between AT-rich DNA. Recent genome-wide chromosome organization studies showed that remote contact frequencies are higher for AT-rich and methylated DNA, suggesting that direct DNA-DNA interactions that we report here may play a role in the chromosome organization and gene regulation.

  11. Evidence for the direct decay of the 125 GeV Higgs boson to fermions

    Chatrchyan, Serguei; Sirunyan, Albert M; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Luyckx, Sten; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Heracleous, Natalie; Kalogeropoulos, Alexis; Keaveney, James; Kim, Tae Jeong; Lowette, Steven; Maes, Michael; Olbrechts, Annik; Python, Quentin; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Favart, Laurent; Gay, Arnaud; Léonard, Alexandre; Marage, Pierre Edouard; Mohammadi, Abdollah; Perniè, Luca; Reis, Thomas; Seva, Tomislav; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Costantini, Silvia; Crucy, Shannon; Dildick, Sven; Garcia, Guillaume; Klein, Benjamin; Lellouch, Jérémie; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Salva Diblen, Sinem; Sigamani, Michael; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Walsh, Sinead; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bruno, Giacomo; Castello, Roberto; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Liao, Junhui; Militaru, Otilia; Nuttens, Claude; Pagano, Davide; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Alves, Gilvan; Correa Martins Junior, Marcos; Dos Reis Martins, Thiago; Pol, Maria Elena; Henrique Gomes E Souza, Moacyr; Aldá Júnior, Walter Luiz; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Malbouisson, Helena; Malek, Magdalena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santaolalla, Javier; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Bernardes, Cesar Augusto; De Almeida Dias, Flavia; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Genchev, Vladimir; Iaydjiev, Plamen; Marinov, Andrey; Piperov, Stefan; Rodozov, Mircho; Sultanov, Georgi; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Du, Ran; Jiang, Chun-Hua; Liang, Dong; Liang, Song; Meng, Xiangwei; Plestina, Roko; Tao, Junquan; Wang, Xianyou; Wang, Zheng; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Qiang; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Mekterovic, Darko; Morovic, Srecko; Sudic, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Bodlak, Martin; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; Elgammal, Sherif; Ellithi Kamel, Ali; Mahmoud, Mohammed; Mahrous, Ayman; Radi, Amr; Kadastik, Mario; Müntel, Mait; Murumaa, Marion; Raidal, Martti; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Nayak, Aruna; Rander, John; Rosowsky, André; Titov, Maksym; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Charlot, Claude; Daci, Nadir; Dahms, Torsten; Dalchenko, Mykhailo; Dobrzynski, Ludwik; Filipovic, Nicolas; Florent, Alice; Granier de Cassagnac, Raphael; Mastrolorenzo, Luca; Miné, Philippe; Mironov, Camelia; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Paganini, Pascal; Sabes, David; Salerno, Roberto; Sauvan, Jean-baptiste; Sirois, Yves; Veelken, Christian; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Bloch, Daniel; Brom, Jean-Marie; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Drouhin, Frédéric; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Juillot, Pierre; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Beaupere, Nicolas; Boudoul, Gaelle; Brochet, Sébastien; Carrillo Montoya, Camilo Andres; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Kurca, Tibor; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Ruiz Alvarez, José David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Xiao, Hong; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Bontenackels, Michael; Calpas, Betty; Edelhoff, Matthias; Feld, Lutz; Hindrichs, Otto; Klein, Katja; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Sprenger, Daniel; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Caudron, Julien; Dietz-Laursonn, Erik; Duchardt, Deborah; Erdmann, Martin; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Weber, Martin; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Haj Ahmad, Wael; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Lingemann, Joschka; Nowack, Andreas; Nugent, Ian Michael; Perchalla, Lars; Pooth, Oliver; Stahl, Achim; Asin, Ivan; Bartosik, Nazar; Behr, Joerg; Behrenhoff, Wolf; Behrens, Ulf; Bell, Alan James; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Burgmeier, Armin; Cakir, Altan; Calligaris, Luigi; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Geiser, Achim; Grebenyuk, Anastasia; Gunnellini, Paolo; Habib, Shiraz; Hauk, Johannes; Hellwig, Gregor; Hempel, Maria; Horton, Dean; Jung, Hannes; Kasemann, Matthias; Katsas, Panagiotis; Kieseler, Jan; Kleinwort, Claus; Krämer, Mira; Krücker, Dirk; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lohmann, Wolfgang; Lutz, Benjamin; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Novgorodova, Olga; Nowak, Friederike; Ntomari, Eleni; Perrey, Hanno; Petrukhin, Alexey; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Ribeiro Cipriano, Pedro M; Riedl, Caroline; Ron, Elias; Sahin, Mehmet Özgür; Salfeld-Nebgen, Jakob; Saxena, Pooja; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Schröder, Matthias; Stein, Matthias; Vargas Trevino, Andrea Del Rocio; Walsh, Roberval; Wissing, Christoph; Aldaya Martin, Maria; Blobel, Volker; Centis Vignali, Matteo; Enderle, Holger; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Görner, Martin; Gosselink, Martijn; Haller, Johannes; Höing, Rebekka Sophie; Kirschenmann, Henning; Klanner, Robert; Kogler, Roman; Lange, Jörn; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Ott, Jochen; Peiffer, Thomas; Pietsch, Niklas; Rathjens, Denis; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Seidel, Markus; Sibille, Jennifer; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Feindt, Michael; Guthoff, Moritz; Hartmann, Frank; Hauth, Thomas; Held, Hauke; Hoffmann, Karl-Heinz; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Kuznetsova, Ekaterina; Lobelle Pardo, Patricia; Martschei, Daniel; Mozer, Matthias Ulrich; Müller, Thomas; Niegel, Martin; Nürnberg, Andreas; Oberst, Oliver; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Röcker, Steffen; Schilling, Frank-Peter; Schott, Gregory; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weiler, Thomas; Wolf, Roger; Zeise, Manuel; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kesisoglou, Stilianos; Kyriakis, Aristotelis; Loukas, Demetrios; Markou, Athanasios; Markou, Christos; Psallidas, Andreas; Topsis-Giotis, Iasonas; Gouskos, Loukas; Panagiotou, Apostolos; Saoulidou, Niki; Stiliaris, Efstathios; Aslanoglou, Xenofon; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Jones, John; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Bencze, Gyorgy; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Karancsi, János; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Swain, Sanjay Kumar; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Kaur, Manjit; Mittal, Monika; Nishu, Nishu; Sharma, Archana; Singh, Jasbir; Kumar, Ashok; Kumar, Arun; Ahuja, Sudha; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Varun; Shivpuri, Ram Krishen; Banerjee, Sunanda; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dutta, Suchandra; Gomber, Bhawna; Jain, Sandhya; Jain, Shilpi; Khurana, Raman; Modak, Atanu; Mukherjee, Swagata; Roy, Debarati; Sarkar, Subir; Sharan, Manoj; Singh, Anil; Abdulsalam, Abdulla; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Chatterjee, Rajdeep Mohan; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Parida, Bibhuti; Sudhakar, Katta; Wickramage, Nadeesha; Banerjee, Sudeshna; Dewanjee, Ram Krishna; Dugad, Shashikant; Arfaei, Hessamaddin; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Jafari, Abideh; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Safarzadeh, Batool; Zeinali, Maryam; Grunewald, Martin; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Chhibra, Simranjit Singh; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; My, Salvatore; Nuzzo, Salvatore; Pacifico, Nicola; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Selvaggi, Giovanna; Silvestris, Lucia; Singh, Gurpreet; Venditti, Rosamaria; Verwilligen, Piet; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Meneghelli, Marco; Montanari, Alessandro; Navarria, Francesco; Odorici, Fabrizio; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gallo, Elisabetta; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Fabbricatore, Pasquale; Ferro, Fabrizio; Lo Vetere, Maurizio; Musenich, Riccardo; Robutti, Enrico; Tosi, Silvano; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Lucchini, Marco Toliman; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Martelli, Arabella; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bisello, Dario; Branca, Antonio; Carlin, Roberto; Checchia, Paolo; Dorigo, Tommaso; Galanti, Mario; Gasparini, Fabrizio; Gasparini, Ugo; Giubilato, Piero; Gonella, Franco; Gozzelino, Andrea; Kanishchev, Konstantin; Lacaprara, Stefano; Lazzizzera, Ignazio; Margoni, Martino; Meneguzzo, Anna Teresa; Montecassiano, Fabio; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Torassa, Ezio; Tosi, Mia; Vanini, Sara; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Gabusi, Michele; Ratti, Sergio P; Riccardi, Cristina; Salvini, Paola; Vitulo, Paolo; Biasini, Maurizio; Bilei, Gian Mario; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Romeo, Francesco; Saha, Anirban; Santocchia, Attilio; Spiezia, Aniello; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Kraan, Aafke; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Moon, Chang-Seong; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Squillacioti, Paola; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Vernieri, Caterina; Barone, Luciano; Cavallari, Francesca; Del Re, Daniele; Diemoz, Marcella; Grassi, Marco; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Micheli, Francesco; Nourbakhsh, Shervin; Organtini, Giovanni; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Soffi, Livia; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Casasso, Stefano; Costa, Marco; Degano, Alessandro; Demaria, Natale; Finco, Linda; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Ortona, Giacomo; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Montanino, Damiana; Schizzi, Andrea; Umer, Tomo; Zanetti, Anna; Chang, Sunghyun; Kim, Tae Yeon; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Ji Eun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Park, Hyangkyu; Sakharov, Alexandre; Son, Dong-Chul; Kim, Jae Yool; Kim, Zero Jaeho; Song, Sanghyeon; Choi, Suyong; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Byounghoon; Lee, Kyong Sei; Park, Sung Keun; Roh, Youn; Choi, Minkyoo; Kim, Ji Hyun; Park, Chawon; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kwon, Eunhyang; Lee, Jongseok; Seo, Hyunkwan; Yu, Intae; Juodagalvis, Andrius; Komaragiri, Jyothsna Rani; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Martínez-Ortega, Jorge; Sánchez Hernández, Alberto; Villasenor-Cendejas, Luis Manuel; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Doesburg, Robert; Reucroft, Steve; Ahmad, Ashfaq; Ahmad, Muhammad; Asghar, Muhammad Irfan; Butt, Jamila; Hassan, Qamar; Hoorani, Hafeez R; Khan, Wajid Ali; Khurshid, Taimoor; Qazi, Shamona; Shah, Mehar Ali; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Wrochna, Grzegorz; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Wolszczak, Weronika; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Varela, Joao; Vischia, Pietro; Golutvin, Igor; Gorbunov, Ilya; Karjavin, Vladimir; Konoplyanikov, Viktor; Korenkov, Vladimir; Kozlov, Guennady; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Savina, Maria; Shmatov, Sergey; Shulha, Siarhei; Skatchkov, Nikolai; Smirnov, Vitaly; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Spiridonov, Alexander; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Vinogradov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Obraztsov, Stepan; Perfilov, Maxim; Petrushanko, Sergey; Savrin, Viktor; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Djordjevic, Milos; Ekmedzic, Marko; Milosevic, Jovan; Aguilar-Benitez, Manuel; Alcaraz Maestre, Juan; Battilana, Carlo; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Ferrando, Antonio; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Merino, Gonzalo; Navarro De Martino, Eduardo; Pérez Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; Willmott, Carlos; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Brun, Hugues; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Lloret Iglesias, Lara; Brochero Cifuentes, Javier Andres; Cabrillo, Iban Jose; Calderon, Alicia; Duarte Campderros, Jordi; Fernandez, Marcos; Gomez, Gervasio; Gonzalez Sanchez, Javier; Graziano, Alberto; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Benaglia, Andrea; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Bernet, Colin; Bianchi, Giovanni; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Bondu, Olivier; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Cerminara, Gianluca; Christiansen, Tim; Coarasa Perez, Jose Antonio; Colafranceschi, Stefano; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; David Tinoco Mendes, Andre; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Dobson, Marc; Dupont-Sagorin, Niels; Elliott-Peisert, Anna; Eugster, Jürg; Franzoni, Giovanni; Funk, Wolfgang; Giffels, Manuel; Gigi, Dominique; Gill, Karl; Girone, Maria; Giunta, Marina; Glege, Frank; Gomez-Reino Garrido, Robert; Gowdy, Stephen; Guida, Roberto; Hammer, Josef; Hansen, Magnus; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Karavakis, Edward; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Mulders, Martijn; Musella, Pasquale; Orsini, Luciano; Palencia Cortezon, Enrique; Pape, Luc; Perez, Emmanuelle; Perrozzi, Luca; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Pimiä, Martti; Piparo, Danilo; Plagge, Michael; Racz, Attila; Reece, William; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Santanastasio, Francesco; Schäfer, Christoph; Schwick, Christoph; Sekmen, Sezen; Sharma, Archana; Siegrist, Patrice; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Treille, Daniel; Tsirou, Andromachi; Veres, Gabor Istvan; Vlimant, Jean-Roch; Wöhri, Hermine Katharina; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; König, Stefan; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Bortignon, Pierluigi; Buchmann, Marco-Andrea; Casal, Bruno; Chanon, Nicolas; Deisher, Amanda; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Dünser, Marc; Eller, Philipp; Grab, Christoph; Hits, Dmitry; Lustermann, Werner; Mangano, Boris; Marini, Andrea Carlo; Martinez Ruiz del Arbol, Pablo; Meister, Daniel; Mohr, Niklas; Nägeli, Christoph; Nef, Pascal; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pauss, Felicitas; Peruzzi, Marco; Quittnat, Milena; Rebane, Liis; Ronga, Frederic Jean; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Theofilatos, Konstantinos; Wallny, Rainer; Weber, Hannsjoerg Artur; Amsler, Claude; Canelli, Maria Florencia; Chiochia, Vincenzo; De Cosa, Annapaola; Hinzmann, Andreas; Hreus, Tomas; Ivova Rikova, Mirena; Kilminster, Benjamin; Millan Mejias, Barbara; Ngadiuba, Jennifer; Robmann, Peter; Snoek, Hella; Taroni, Silvia; Verzetti, Mauro; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Ferro, Cristina; Kuo, Chia-Ming; Li, Syue-Wei; Lin, Willis; Lu, Yun-Ju; Volpe, Roberta; Yu, Shin-Shan; Bartalini, Paolo; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Grundler, Ulysses; Hou, George Wei-Shu; Hsiung, Yee; Kao, Kai-Yi; Lei, Yeong-Jyi; Liu, Yueh-Feng; Lu, Rong-Shyang; Majumder, Devdatta; Petrakou, Eleni; Shi, Xin; Shiu, Jing-Ge; Tzeng, Yeng-Ming; Wang, Minzu; Wilken, Rachel; Asavapibhop, Burin; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Akin, Ilina Vasileva; Aliev, Takhmasib; Bilin, Bugra; Bilmis, Selcuk; Deniz, Muhammed; Gamsizkan, Halil; Guler, Ali Murat; Karapinar, Guler; Ocalan, Kadir; Ozpineci, Altug; Serin, Meltem; Sever, Ramazan; Surat, Ugur Emrah; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Ozkorucuklu, Suat; Bahtiyar, Hüseyin; Barlas, Esra; Cankocak, Kerem; Günaydin, Yusuf Oguzhan; Vardarli, Fuat Ilkehan; Yücel, Mete; Levchuk, Leonid; Sorokin, Pavel; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Frazier, Robert; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Senkin, Sergey; Smith, Vincent J; Williams, Thomas; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Ilic, Jelena; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Burton, Darren; Colling, David; Cripps, Nicholas; Cutajar, Michael; Dauncey, Paul; Davies, Gavin; Della Negra, Michel; Ferguson, William; Fulcher, Jonathan; Futyan, David; Gilbert, Andrew; Guneratne Bryer, Arlo; Hall, Geoffrey; Hatherell, Zoe; Hays, Jonathan; Iles, Gregory; Jarvis, Martyn; Karapostoli, Georgia; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Marrouche, Jad; Mathias, Bryn; Nandi, Robin; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Pioppi, Michele; Raymond, David Mark; Rogerson, Samuel; Rose, Andrew; Seez, Christopher; Sharp, Peter; Sparrow, Alex; Tapper, Alexander; Vazquez Acosta, Monica; Virdee, Tejinder; Wakefield, Stuart; Wardle, Nicholas; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Martin, William; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Dittmann, Jay; Hatakeyama, Kenichi; Kasmi, Azeddine; Liu, Hongxuan; Scarborough, Tara; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Heister, Arno; Lawson, Philip; Lazic, Dragoslav; Richardson, Clint; Rohlf, James; Sperka, David; St John, Jason; Sulak, Lawrence; Alimena, Juliette; Bhattacharya, Saptaparna; Christopher, Grant; Cutts, David; Demiragli, Zeynep; Ferapontov, Alexey; Garabedian, Alex; Heintz, Ulrich; Jabeen, Shabnam; Kukartsev, Gennadiy; Laird, Edward; Landsberg, Greg; Luk, Michael; Narain, Meenakshi; Segala, Michael; Sinthuprasith, Tutanon; Speer, Thomas; Swanson, Joshua; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Kopecky, Alexandra; Lander, Richard; Miceli, Tia; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Rutherford, Britney; Searle, Matthew; Shalhout, Shalhout; Smith, John; Squires, Michael; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Andreev, Valeri; Cline, David; Cousins, Robert; Erhan, Samim; Everaerts, Pieter; Farrell, Chris; Felcini, Marta; Hauser, Jay; Ignatenko, Mikhail; Jarvis, Chad; Rakness, Gregory; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Babb, John; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Jandir, Pawandeep; Lacroix, Florent; Liu, Hongliang; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Nguyen, Harold; Shrinivas, Amithabh; Sturdy, Jared; Sumowidagdo, Suharyo; Wimpenny, Stephen; Andrews, Warren; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Evans, David; Holzner, André; Kelley, Ryan; Kovalskyi, Dmytro; Lebourgeois, Matthew; Letts, James; Macneill, Ian; Padhi, Sanjay; Palmer, Christopher; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Sudano, Elizabeth; Tadel, Matevz; Tu, Yanjun; Vartak, Adish; Wasserbaech, Steven; Würthwein, Frank; Yagil, Avraham; Yoo, Jaehyeok; Barge, Derek; Bradmiller-Feld, John; Campagnari, Claudio; Danielson, Thomas; Dishaw, Adam; Flowers, Kristen; Franco Sevilla, Manuel; Geffert, Paul; George, Christopher; Golf, Frank; Incandela, Joe; Justus, Christopher; Magaña Villalba, Ricardo; Mccoll, Nickolas; Pavlunin, Viktor; Richman, Jeffrey; Rossin, Roberto; Stuart, David; To, Wing; West, Christopher; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Di Marco, Emanuele; Duarte, Javier; Kcira, Dorian; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Rogan, Christopher; Spiropulu, Maria; Timciuc, Vladlen; Wilkinson, Richard; Xie, Si; Zhu, Ren-Yuan; Azzolini, Virginia; Calamba, Aristotle; Carroll, Ryan; Ferguson, Thomas; Iiyama, Yutaro; Jang, Dong Wook; Paulini, Manfred; Russ, James; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Drell, Brian Robert; Ford, William T; Gaz, Alessandro; Luiggi Lopez, Eduardo; Nauenberg, Uriel; Smith, James; Stenson, Kevin; Ulmer, Keith; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Chu, Jennifer; Eggert, Nicholas; Gibbons, Lawrence Kent; Hopkins, Walter; Khukhunaishvili, Aleko; Kreis, Benjamin; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Ryd, Anders; Salvati, Emmanuele; Sun, Werner; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Winstrom, Lucas; Wittich, Peter; Winn, Dave; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Burkett, Kevin; Butler, Joel Nathan; Chetluru, Vasundhara; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gao, Yanyan; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hare, Daryl; Harris, Robert M; Hirschauer, James; Hooberman, Benjamin; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Kaadze, Ketino; Klima, Boaz; Kwan, Simon; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Tiehui; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Mishra, Kalanand; Mrenna, Stephen; Musienko, Yuri; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Prokofyev, Oleg; Ratnikova, Natalia; Sexton-Kennedy, Elizabeth; Sharma, Seema; Soha, Aron; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vidal, Richard; Whitbeck, Andrew; Whitmore, Juliana; Wu, Weimin; Yang, Fan; Yun, Jae Chul; Acosta, Darin; Avery, Paul; Bourilkov, Dimitri; Cheng, Tongguang; Das, Souvik; De Gruttola, Michele; Di Giovanni, Gian Piero; Dobur, Didar; Field, Richard D; Fisher, Matthew; Fu, Yu; Furic, Ivan-Kresimir; Hugon, Justin; Kim, Bockjoo; Konigsberg, Jacobo; Korytov, Andrey; Kropivnitskaya, Anna; Kypreos, Theodore; Low, Jia Fu; Matchev, Konstantin; Milenovic, Predrag; Mitselmakher, Guenakh; Muniz, Lana; Rinkevicius, Aurelijus; Shchutska, Lesya; Skhirtladze, Nikoloz; Snowball, Matthew; Yelton, John; Zakaria, Mohammed; Gaultney, Vanessa; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Chen, Jie; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Prosper, Harrison; Veeraraghavan, Venkatesh; Weinberg, Marc; Baarmand, Marc M; Dorney, Brian; Hohlmann, Marcus; Kalakhety, Himali; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Bazterra, Victor Eduardo; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Khalatyan, Samvel; Kurt, Pelin; Moon, Dong Ho; O'Brien, Christine; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Akgun, Ugur; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Duru, Firdevs; Haytmyradov, Maksat; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Rahmat, Rahmat; Sen, Sercan; Tan, Ping; Tiras, Emrah; Wetzel, James; Yetkin, Taylan; Yi, Kai; Barnett, Bruce Arnold; Blumenfeld, Barry; Bolognesi, Sara; Fehling, David; Gritsan, Andrei; Maksimovic, Petar; Martin, Christopher; Swartz, Morris; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Gray, Julia; Kenny III, Raymond Patrick; Murray, Michael; Noonan, Daniel; Sanders, Stephen; Sekaric, Jadranka; Stringer, Robert; Wang, Quan; Wood, Jeffrey Scott; Barfuss, Anne-Fleur; Chakaberia, Irakli; Ivanov, Andrew; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Saini, Lovedeep Kaur; Shrestha, Shruti; Svintradze, Irakli; Gronberg, Jeffrey; Lange, David; Rebassoo, Finn; Wright, Douglas; Baden, Drew; Calvert, Brian; Eno, Sarah Catherine; Gomez, Jaime; Hadley, Nicholas John; Kellogg, Richard G; Kolberg, Ted; Lu, Ying; Marionneau, Matthieu; Mignerey, Alice; Pedro, Kevin; Skuja, Andris; Temple, Jeffrey; Tonjes, Marguerite; Tonwar, Suresh C; Apyan, Aram; Barbieri, Richard; Bauer, Gerry; Busza, Wit; Cali, Ivan Amos; Chan, Matthew; Di Matteo, Leonardo; Dutta, Valentina; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Klute, Markus; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Ma, Teng; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Stephans, George; Stöckli, Fabian; Sumorok, Konstanty; Velicanu, Dragos; Veverka, Jan; Wyslouch, Bolek; Yang, Mingming; Yoon, Sungho; Zanetti, Marco; Zhukova, Victoria; Dahmes, Bryan; De Benedetti, Abraham; Gude, Alexander; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Mans, Jeremy; Pastika, Nathaniel; Rusack, Roger; Singovsky, Alexander; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Cremaldi, Lucien Marcus; Kroeger, Rob; Oliveros, Sandra; Perera, Lalith; Sanders, David A; Summers, Don; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Gonzalez Suarez, Rebeca; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Lazo-Flores, Jose; Malik, Sudhir; Meier, Frank; Snow, Gregory R; Dolen, James; Godshalk, Andrew; Iashvili, Ia; Jain, Supriya; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Haley, Joseph; Massironi, Andrea; Nash, David; Orimoto, Toyoko; Trocino, Daniele; Wood, Darien; Zhang, Jinzhong; Anastassov, Anton; Hahn, Kristan Allan; Kubik, Andrew; Lusito, Letizia; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Velasco, Mayda; Won, Steven; Berry, Douglas; Brinkerhoff, Andrew; Chan, Kwok Ming; Drozdetskiy, Alexey; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Kolb, Jeff; Lannon, Kevin; Luo, Wuming; Lynch, Sean; Marinelli, Nancy; Morse, David Michael; Pearson, Tessa; Planer, Michael; Ruchti, Randy; Slaunwhite, Jason; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hill, Christopher; Hughes, Richard; Kotov, Khristian; Ling, Ta-Yung; Puigh, Darren; Rodenburg, Marissa; Smith, Geoffrey; Vuosalo, Carl; Winer, Brian L; Wolfe, Homer; Wulsin, Howard Wells; Berry, Edmund; Elmer, Peter; Halyo, Valerie; Hebda, Philip; Hunt, Adam; Jindal, Pratima; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Piroué, Pierre; Quan, Xiaohang; Raval, Amita; Saka, Halil; Stickland, David; Tully, Christopher; Werner, Jeremy Scott; Zenz, Seth Conrad; Zuranski, Andrzej; Brownson, Eric; Lopez, Angel; Mendez, Hector; Ramirez Vargas, Juan Eduardo; Alagoz, Enver; Benedetti, Daniele; Bolla, Gino; Bortoletto, Daniela; De Mattia, Marco; Everett, Adam; Hu, Zhen; Jha, Manoj; Jones, Matthew; Jung, Kurt; Kress, Matthew; Leonardo, Nuno; Lopes Pegna, David; Maroussov, Vassili; Merkel, Petra; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shipsey, Ian; Silvers, David; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Yoo, Hwi Dong; Zablocki, Jakub; Zheng, Yu; Parashar, Neeti; Adair, Antony; Akgun, Bora; Ecklund, Karl Matthew; Geurts, Frank JM; Li, Wei; Michlin, Benjamin; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Zabel, James; Betchart, Burton; Bodek, Arie; Covarelli, Roberto; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Garcia-Bellido, Aran; Goldenzweig, Pablo; Han, Jiyeon; Harel, Amnon; Miner, Daniel Carl; Petrillo, Gianluca; Vishnevskiy, Dmitry; Zielinski, Marek; Bhatti, Anwar; Ciesielski, Robert; Demortier, Luc; Goulianos, Konstantin; Lungu, Gheorghe; Malik, Sarah; Mesropian, Christina; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Lath, Amitabh; Panwalkar, Shruti; Park, Michael; Patel, Rishi; Rekovic, Vladimir; Robles, Jorge; Salur, Sevil; Schnetzer, Steve; Seitz, Claudia; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Rose, Keith; Spanier, Stefan; Yang, Zong-Chang; York, Andrew; Bouhali, Othmane; Eusebi, Ricardo; Flanagan, Will; Gilmore, Jason; Kamon, Teruki; Khotilovich, Vadim; Krutelyov, Vyacheslav; Montalvo, Roy; Osipenkov, Ilya; Pakhotin, Yuriy; Perloff, Alexx; Roe, Jeffrey; Rose, Anthony; Safonov, Alexei; Sakuma, Tai; Suarez, Indara; Tatarinov, Aysen; Toback, David; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Kovitanggoon, Kittikul; Kunori, Shuichi; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Sharma, Monika; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Boutle, Sarah; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Lin, Chuanzhe; Neu, Christopher; Wood, John; Gollapinni, Sowjanya; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Belknap, Donald; Borrello, Laura; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Duric, Senka; Friis, Evan; Grothe, Monika; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Klukas, Jeffrey; Lanaro, Armando; Lazaridis, Christos; Levine, Aaron; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ross, Ian; Sarangi, Tapas; Savin, Alexander; Smith, Wesley H; Woods, Nathaniel

    2014-06-22

    The discovery of a new boson with a mass of approximately 125 GeV in 2012 at the LHC has heralded a new era in understanding the nature of electroweak symmetry breaking and possibly completing the standard model of particle physics. Since the first observation in decays to gamma-gamma, WW, and ZZ boson pairs, an extensive set of measurements of the mass and couplings to W and Z bosons, as well as multiple tests of the spin-parity quantum numbers, have revealed that the properties of the new boson are consistent with those of the long-sought agent responsible for electroweak symmetry breaking. An important open question is whether the new particle also couples to fermions, and in particular to down-type fermions, since the current measurements mainly constrain the couplings to the up-type top quark. Determination of the couplings to down-type fermions requires direct measurement of the corresponding Higgs boson decays, as recently reported by the CMS experiment in the study of Higgs decays to bottom quarks and...

  12. Intentional forgetting reduces color-naming interference: evidence from item-method directed forgetting.

    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 remaining half of the probe items were a repetition of the preceding study item. Repeated probe items were either identical to the preceding study item (E1, E2), a phonetic reproduction of the preceding study item (E3), or perceptually matched to the preceding study item (E4). Color-naming interference was calculated by subtracting color-naming reaction times made in response to a string of meaningless symbols from that of the novel and repeated conditions. Across all experiments, participants recalled more to-be-remembered (TBR) than to-be-forgotten (TBF) study words. More importantly, Experiments 1 and 2 found that color-naming interference was reduced for repeated TBF words relative to repeated TBR words. Experiments 3 and 4 further found that this effect occurred at the perceptual rather than semantic level. These findings suggest that participants may bias processing resources away from the perceptual representation of to-be-forgotten information.

  13. Emotion and goal-directed behavior: ERP evidence on cognitive and emotional conflict.

    Zinchenko, Artyom; Kanske, Philipp; Obermeier, Christian; Schröger, Erich; Kotz, Sonja A

    2015-11-01

    Cognitive control supports goal-directed behavior by resolving conflict among opposing action tendencies. Emotion can trigger cognitive control processes, thus speeding up conflict processing when the target dimension of stimuli is emotional. However, it is unclear what role emotionality of the target dimension plays in the processing of emotional conflict (e.g. in irony). In two EEG experiments, we compared the influence of emotional valence of the target (emotional, neutral) in cognitive and emotional conflict processing. To maximally approximate real-life communication, we used audiovisual stimuli. Participants either categorized spoken vowels (cognitive conflict) or their emotional valence (emotional conflict), while visual information was congruent or incongruent. Emotional target dimension facilitated both cognitive and emotional conflict processing, as shown in a reduced reaction time conflict effect. In contrast, the N100 in the event-related potentials showed a conflict-specific reversal: the conflict effect was larger for emotional compared with neutral trials in cognitive conflict and smaller in emotional conflict. Additionally, domain-general conflict effects were observed in the P200 and N200 responses. The current findings confirm that emotions have a strong influence on cognitive and emotional conflict processing. They also highlight the complexity and heterogeneity of the interaction of emotion with different types of conflict. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

    Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

    2018-01-01

    This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI. PMID:29382112

  15. Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

    Jiangfeng Hu

    2018-01-01

    Full Text Available This study examines the spillover effects of foreign direct investment (FDI on green technology progress rate (as measured by the green total factor productivity. The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

  16. First direct evidence of long-distance seasonal movements and hibernation in a migratory bat

    Weller, Theodore J.; Castle, Kevin T.; Liechti, Felix; Hein, Cris D.; Schirmacher, Michael R.; Cryan, Paul M.

    2016-01-01

    Understanding of migration in small bats has been constrained by limitations of techniques that were labor-intensive, provided coarse levels of resolution, or were limited to population-level inferences. Knowledge of movements and behaviors of individual bats have been unknowable because of limitations in size of tracking devices and methods to attach them for long periods. We used sutures to attach miniature global positioning system (GPS) tags and data loggers that recorded light levels, activity, and temperature to male hoary bats (Lasiurus cinereus). Results from recovered GPS tags illustrated profound differences among movement patterns by individuals, including one that completed a >1000 km round-trip journey during October 2014. Data loggers allowed us to record sub-hourly patterns of activity and torpor use, in one case over a period of 224 days that spanned an entire winter. In this latter bat, we documented 5 torpor bouts that lasted ≥16 days and a flightless period that lasted 40 nights. These first uses of miniature tags on small bats allowed us to discover that male hoary bats can make multi-directional movements during the migratory season and sometimes hibernate for an entire winter.

  17. Environmental Regulation, Foreign Direct Investment and Green Technological Progress-Evidence from Chinese Manufacturing Industries.

    Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

    2018-01-29

    This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications-high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

  18. Evidence on the determinants of foreign direct investment: the case of EU regions

    Laura RESMINI

    2010-12-01

    Full Text Available This study analyses the determinants of Foreign Direct Investment (FDI at regional level. While the determinants of FDI in Europe have been extensively analysed at the country level, the literature on location patterns and on the determinants of FDI at the regional level is only at its beginning. This study follows this line of empirical research by using original data on the number of foreign investments over the 2005-07 period disaggregated by regions of the EU27 and by sectors. We perform a detailed analysis of the location determinants of foreign investments using different econometric specifications in order to consider a large set of variables potentially explaining FDI location. We attempt, on the one hand, to demonstrate whether variables usually employed to explain the determinants of FDI at the country level also influence the location of FDI at the regional level, and on the other hand to identify which locational advantages are able to attract FDI into EU regions. In so doing, we control for firm, sector and spatial heterogeneity in order to capture potential differences in the patterns of location of different kinds of foreign firms.

  19. Economic Determinants of Foreign Direct Investment in Armenia, Kyrgyz Republic and Turkmenistan: Theory and Evidence

    Muhammad AZAM

    2010-11-01

    Full Text Available The aim of the present study is to investigate the effects of different economic determinants on foreign direct investment (FDI for three countries selected from Central Asia namely Armenia, Kyrgyz Republic and Turkmenistan. Secondary data for the period from 1991 to 2009 taken from World Development Indicator (various issues have been utilized. Simple econometric model in log form and the least squares technique have been used. Result found indicates positive effects of market size, official development assistance on FDI and negative effect of inflation on FDI. However, in case of Armenia, the effect of official development assistance on FDI has been found insignificant and such as in case of Kyrgyz Republic, the effect of inflation on FDI has been found insignificant with expected negative sign. Thus, findings of the study recommend that market size and official development assistance needs to be encouraged and inflation needs to be managed in order to achieve higher level of FDI and accelerate the process of economic development.

  20. Evidence for the direct ejection of clusters from non-metallic solids during laser vaporization

    Bloomfield, L.A.; Yang, Y.A.; Xia, P.; Junkin, A.L.

    1991-01-01

    This paper reports on the formation of molecular scale particles or clusters of alkali halides and semiconductors during laser vaporization of solids. By measuring the abundances of cluster ions produced in several different source configurations, the authors have determined that clusters are ejected directly from the source sample and do not need to grow from atomic or molecular vapor. Using samples of mixed alkali halide powders, the authors have found that unalloyed clusters are easily produced in a source that prevents growth from occurring after the clusters leave the sample surface. However, melting the sample or encouraging growth after vaporization lead to the production of alloyed cluster species. The sizes of the ejected clusters are initially random, but the population spectrum quickly becomes structured as hot, unstable-sized clusters decay into smaller particles. In carbon, large clusters with odd number of atoms decay almost immediately. The hot even clusters also decay, but much more slowly. The longest lived clusters are the magic C 50 and C 60 fullerenes. The mass spectrum of large carbon clusters evolves in time from structureless, to only the even clusters, to primarily C 50 and C 60 . If cluster growth is encouraged, the odd clusters reappear and the population spectrum again becomes relatively structureless

  1. New Directions for Natural Killer T Cells in the Immunotherapy of Cancer

    Luc Teyton

    2017-11-01

    Full Text Available Natural killer T (NKT cells have been placed at the interface between innate and adaptive immunity by a long series of experiments that convincingly showed that beyond cytokine secretion and NK cell recruitment, NKT cells were coordinating dendritic cell and B cell maturation through direct membrane contacts and initiate productive responses. As such, NKT cells are the cellular adjuvant of many immune reactions and have functions that go much beyond what their name encapsulates. In addition, the initial discovery of the ligands of NKT cells is deeply linked to cancer biology and therapy. However, for a host of reasons, animal models in which agonists of NKT cells were used did not translate well to human cancers. A systematic reassessment of NKT cells role in tumorigenesis, especially spontaneous one, is now accessible using single cell analysis technologies both in mouse and man, and should be taken advantage of. Similarly, the migration, localization, phenotype of NKT cells following induced expansion after injection of an agonist can be examined at the single cell level. This technological revolution will help evaluate where and how NKT cells can be used in cancer.

  2. Visualization of anomalous Ettingshausen effect in a ferromagnetic film: Direct evidence of different symmetry from spin Peltier effect

    Seki, T.; Iguchi, R.; Takanashi, K.; Uchida, K.

    2018-04-01

    Spatial distribution of temperature modulation due to the anomalous Ettingshausen effect (AEE) is visualized in a ferromagnetic FePt thin film with in-plane and out-of-plane magnetizations using the lock-in thermography technique. Comparing the AEE of FePt with the spin Peltier effect (SPE) of a Pt/yttrium iron garnet junction provides direct evidence of different symmetries of AEE and SPE. Our experiments and numerical calculations reveal that the distribution of heat sources induced by AEE strongly depends on the direction of magnetization, leading to the remarkable different temperature profiles in the FePt thin film between the in-plane and perpendicularly magnetized configurations.

  3. Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells.

    Bargaje, Rhishikesh; Trachana, Kalliopi; Shelton, Martin N; McGinnis, Christopher S; Zhou, Joseph X; Chadick, Cora; Cook, Savannah; Cavanaugh, Christopher; Huang, Sui; Hood, Leroy

    2017-02-28

    Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.

  4. Direct digestion of proteins in living cells into peptides for proteomic analysis.

    Chen, Qi; Yan, Guoquan; Gao, Mingxia; Zhang, Xiangmin

    2015-01-01

    To analyze the proteome of an extremely low number of cells or even a single cell, we established a new method of digesting whole cells into mass-spectrometry-identifiable peptides in a single step within 2 h. Our sampling method greatly simplified the processes of cell lysis, protein extraction, protein purification, and overnight digestion, without compromising efficiency. We used our method to digest hundred-scale cells. As far as we know, there is no report of proteome analysis starting directly with as few as 100 cells. We identified an average of 109 proteins from 100 cells, and with three replicates, the number of proteins rose to 204. Good reproducibility was achieved, showing stability and reliability of the method. Gene Ontology analysis revealed that proteins in different cellular compartments were well represented.

  5. Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors.

    Hidetatsu Outani

    Full Text Available The repair of large cartilage defects with hyaline cartilage continues to be a challenging clinical issue. We recently reported that the forced expression of two reprogramming factors (c-Myc and Klf4 and one chondrogenic factor (SOX9 can induce chondrogenic cells from mouse dermal fibroblast culture without going through a pluripotent state. We here generated induced chondrogenic (iChon cells from human dermal fibroblast (HDF culture with the same factors. We developed a chondrocyte-specific COL11A2 promoter/enhancer lentiviral reporter vector to select iChon cells. The human iChon cells expressed marker genes for chondrocytes but not fibroblasts, and were derived from non-chondrogenic COL11A2-negative cells. The human iChon cells formed cartilage but not tumors in nude mice. This approach could lead to the preparation of cartilage directly from skin in human, without going through pluripotent stem cells.

  6. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  7. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Adam S Zeiger

    Full Text Available Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs via immunocytochemistry, atomic force microscopy (AFM, and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  8. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Zeiger, Adam S; Loe, Felicia C; Li, Ran; Raghunath, Michael; Van Vliet, Krystyn J

    2012-01-01

    Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  9. Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells.

    Tosic, Milica; Allen, Anita; Willmann, Dominica; Lepper, Christoph; Kim, Johnny; Duteil, Delphine; Schüle, Roland

    2018-01-25

    Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.

  10. "Pseudo-Beijing": evidence for convergent evolution in the direct repeat region of Mycobacterium tuberculosis.

    Lukas Fenner

    Full Text Available Mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. One particular M. tuberculosis genotype known as "Beijing" has repeatedly been associated with drug resistance and has been emerging in some parts of the world. "Beijing" strains are traditionally defined based on a characteristic spoligotyping pattern. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC strains exhibiting the typical "Beijing" spoligotyping pattern.MTBC strains were obtained from an ongoing molecular epidemiological study in Switzerland and Nepal. MTBC genotyping was performed based on SNPs, genomic deletions, and 24-loci MIRU-VNTR. We identified three MTBC strains from patients originating from Tibet, Portugal and Nepal which exhibited a spoligotyping patterns identical to the classical Beijing signature. However, based on three alternative molecular markers, these strains were assigned to Lineage 3 (also known as Delhi/CAS rather than to Lineage 2 (also known as East-Asian lineage. Sequencing of the RD207 in one of these strains showed that the deletion responsible for this "Pseudo-Beijing" spoligotype was about 1,000 base pairs smaller than the usual deletion of RD207 in classical "Beijing" strains, which is consistent with an evolutionarily independent deletion event in the direct repeat (DR region of MTBC.We provide an example of convergent evolution in the DR locus of MTBC, and highlight the limitation of using spoligotypes for strain classification. Our results indicate that a proportion of "Beijing" strains may have been misclassified in the past. Markers that are more phylogenetically robust should be used when exploring strain-specific differences in experimental or clinical phenotypes.

  11. Footprints of directional selection in wild Atlantic salmon populations: evidence for parasite-driven evolution?

    Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Lien, Sigbjørn; Primmer, Craig R

    2014-01-01

    Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved.

  12. Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

    Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

    2017-02-01

    Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324. © 2016 AlphaMed Press.

  13. Young driver distraction: state of the evidence and directions for behavior change programs.

    Buckley, Lisa; Chapman, Rebekah L; Sheehan, Mary

    2014-05-01

    Adolescent drivers are overrepresented in distraction-related motor vehicle crashes. A number of potential reasons for such an elevated risk include driving inexperience, high adoption of communication technology, increased peer involvement, and tendency to take risks, which render young drivers particularly vulnerable. Major legislative efforts in Graduated Licensing Systems that include passenger restrictions have shown positive effects. Restrictions on cell phone use are also being introduced; however, it is challenging to enforce such regulations. This article argues that such contextual, legislative interventions are an essential prevention strategy, but there is an unfilled need to introduce behavior change programs that may target adolescents, parents, and friends. A theoretical framework is applied in which risk and protective factors are identified from research within the contexts of community and jurisdiction. In the literature on distraction, social context and normative influences are key elements used to inform program design for adolescent drivers, with parental monitoring informing interventions targeting parents. Following from this assessment of the message content assessment, the design of strategies to deliver the messages is reviewed. In the current literature, school-based programs, simulations, and Web-delivered programs have been evaluated with supplementary strategies delivered by physicians and parents. Such developments are still at an early stage of development, and ultimately will need controlled implementation and evaluation studies. Of course, there is no likely single approach to prevent adolescent driver distraction. Complementary approaches such as the further development of technological interventions to manage phone use are needed. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  14. MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9.

    Li, Jingyuan; Wang, Lijuan; Liu, Zongzhi; Zu, Chao; Xing, Fanfan; Yang, Pei; Yang, Yongkang; Dang, Xiaoqian; Wang, Kunzheng

    2015-09-22

    Accumulating evidence indicates that dysregulation of miRNAs could contribute to tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation and invasion. In the current study, we are interested to examine the role of miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage, we identified miR-494 as a commonly downregulated miRNA in the tissues of patients with chondrosarcoma and chondrosarcoma cancer cell line, and upregulation of miR-494 could inhibit proliferation and invasion of chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells. And downregulation of SOX9 could also inhibit migration and invasion of chondrosarcoma cells. In the last, we identified low expression of miR-494 was significantly correlated with poor overall survival and prognosis of chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and prognosis biomarker for chondrosarcoma.

  15. Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells.

    Lian, Qizhou; Zhang, Yuelin; Liang, Xiaoting; Gao, Fei; Tse, Hung-Fat

    2016-01-01

    Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days. Cells generated with this protocol express typical MSCs surface markers and undergo adipogenesis, osteogenesis, and chondrogenesis similar to adult bone marrow-derived MSCs (BM-MSCs). Nonetheless, compared with adult BM-MSCs, iPSC-MSCs display a higher proliferative capacity, up to 120 passages, without obvious loss of self-renewal potential and constitutively express MSCs surface antigens. MSCs generated with this protocol have numerous applications, including expansion to large scale cell numbers for tissue engineering and the development of cellular therapeutics. This approach has been used to rescue limb ischemia, allergic disorders, and cigarette smoke-induced lung damage and to model mesenchymal and vascular disorders of Hutchinson-Gilford progeria syndrome (HGPS).

  16. Recent Studies on Methanol Crossover in Liquid-Feed Direct Methanol Fuel Cells

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

    2000-01-01

    In this work, the effects of methanol crossover and airflow rates on the cathode potential of an operating direct methanol fuel cell are explored. Techniques for quantifying methanol crossover in a fuel cell and for separating the electrical performance of each electrode in a fuel cell are discussed. The effect of methanol concentration on cathode potential has been determined to be significant. The cathode is found to be mass transfer limited when operating on low flow rate air and high concentrations of methanol. Improvements in cathode structure and operation at low methanol concentration have been shown to result in improved cell performance.

  17. A direct evidence for high carbon dioxide and radon-222 discharge in Central Nepal

    Perrier, F.; Byrdina, S.; Richon, P.; Bollinger, L.; Bureau, S.; Richon, P.; France-Lanord, Ch.; Rajaure, S.; Koirala, Bharat Prasad; Shrestha, Prithvi Lal; Gautam, Umesh Prasad; Tiwari, Dilli Ram; Sapkota, Soma Nath; Revil, A.; Revil, A.; Contraires, S.

    2009-01-01

    Gas discharges have been identified at the Syabru-Bensi hot springs, located at the front of the High Himalaya in Central Nepal, in the Main Central Thrust zone. The hot spring waters are characterized by a temperature reaching 61 C, high salinity, high alkalinity and δ 13 C varying from +0. 7 parts per thousand to +4. 8 parts per thousand. The gas is mainly dry carbon dioxide, with a δ 13 C of -0. 8 parts per thousand. The diffuse carbon dioxide flux, mapped by the accumulation chamber method, reached a value of 19000 g m -2 day -1 , which is comparable with values measured on active volcanoes. Similar values have been observed over a two-year time interval and the integral around the main gas discharge amounts to 0. 25 ± 0. 07 mol s -1 , or 350 ± 100 ton a -1 . The mean radon-222 concentration in spring water did not exceed 2. 5 Bq L -1 , exponentially decreasing with water temperature. In contrast, in gas bubbles collected in the water or in the dry gas discharges, the radon concentration varied from 16 000 to 41000 Bq m -3 . In the soil, radon concentration varied from 25000 to more than 50000 Bq m -3 . Radon flux, measured at more than fifty points, reached extreme values, larger than 2 Bq m -2 s -1 , correlated to the larger values of the carbon dioxide flux. Our direct observation confirms previous studies which indicated large degassing in the Himalaya. The proposed understanding is that carbon dioxide is released at mid-crustal depth by metamorphic reactions within the Indian basement, transported along pre-existing faults by meteoric hot water circulation, and degassed before reaching surface. This work, first, confirms that further studies should be undertaken to better constrain the carbon budget of the Himalaya, and, more generally, the contribution of mountain building to the global carbon balance. Furthermore, the evidenced gas discharges provide a unique natural laboratory for methodological studies, and appear particularly important to study as

  18. Direct evidence for coastal iodine particles from Laminaria macroalgae – linkage to emissions of molecular iodine

    G. McFiggans

    2004-01-01

    Full Text Available Renewal of ultrafine aerosols in the marine boundary layer may lead to repopulation of the marine distribution and ultimately determine the concentration of cloud condensation nuclei (CCN. Thus the formation of nanometre-scale particles can lead to enhanced scattering of incoming radiation and a net cooling of the atmosphere. The recent demonstration of the chamber formation of new particles from the photolytic production of condensable iodine-containing compounds from diiodomethane (CH2I2, (O'Dowd et al., 2002; Kolb, 2002; Jimenez et al., 2003a; Burkholder and Ravishankara, 2003, provides an additional mechanism to the gas-to-particle conversion of sulphuric acid formed in the photo-oxidation of dimethylsulphide for marine aerosol repopulation. CH2I2 is emitted from seaweeds (Carpenter et al., 1999, 2000 and has been suggested as an initiator of particle formation. We demonstrate here for the first time that ultrafine iodine-containing particles are produced by intertidal macroalgae exposed to ambient levels of ozone. The particle composition is very similar both to those formed in the chamber photo-oxidation of diiodomethane and in the oxidation of molecular iodine by ozone. The particles formed in all three systems are similarly aspherical. When small, those formed in the molecular iodine system swell only moderately when exposed to increased humidity environments, and swell progressively less with increasing size; this behaviour occurs whether they are formed in dry or humid environments, in contrast to those in the CH2I2 system. Direct coastal boundary layer observations of molecular iodine, ultrafine particle production and iodocarbons are reported. Using a newly measured molecular iodine photolysis rate, it is shown that, if atomic iodine is involved in the observed particle bursts, it is of the order of at least 1000 times more likely to result from molecular iodine photolysis than diiodomethane photolysis. A hypothesis for molecular

  19. Hemispheric differences in the voluntary control of spatial attention: direct evidence for a right-hemispheric dominance within frontal cortex.

    Duecker, Felix; Formisano, Elia; Sack, Alexander T

    2013-08-01

    Lesion studies in neglect patients have inspired two competing models of spatial attention control, namely, Heilman's "hemispatial" theory and Kinsbourne's "opponent processor" model. Both assume a functional asymmetry between the two hemispheres but propose very different mechanisms. Neuroimaging studies have identified a bilateral dorsal frontoparietal network underlying voluntary shifts of spatial attention. However, lateralization of attentional processes within this network has not been consistently reported. In the current study, we aimed to provide direct evidence concerning the functional asymmetry of the right and left FEF during voluntary shifts of spatial attention. To this end, we applied fMRI-guided neuronavigation to disrupt individual FEF activation foci with a longer-lasting inhibitory patterned TMS protocol followed by a spatial cueing task. Our results indicate that right FEF stimulation impaired the ability of shifting spatial attention toward both hemifields, whereas the effects of left FEF stimulation were limited to the contralateral hemifield. These results provide strong direct evidence for right-hemispheric dominance in spatial attention within frontal cortex supporting Heilman's "hemispatial" theory. This complements previous TMS studies that generally conform to Kinsbourne's "opponent processor" model after disruption of parietal cortex, and we therefore propose that both theories are not mutually exclusive.

  20. Does functional MRI detect activation in white matter? A review of emerging evidence, issues, and future directions

    Gawryluk, Jodie R.; Mazerolle, Erin L.; D'Arcy, Ryan C. N.

    2014-01-01

    Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows for visualization of activated brain regions. Until recently, fMRI studies have focused on gray matter. There are two main reasons white matter fMRI remains controversial: (1) the blood oxygen level dependent (BOLD) fMRI signal depends on cerebral blood flow and volume, which are lower in white matter than gray matter and (2) fMRI signal has been associated with post-synaptic potentials (mainly localized in gray matter) as opposed to action potentials (the primary type of neural activity in white matter). Despite these observations, there is no direct evidence against measuring fMRI activation in white matter and reports of fMRI activation in white matter continue to increase. The questions underlying white matter fMRI activation are important. White matter fMRI activation has the potential to greatly expand the breadth of brain connectivity research, as well as improve the assessment and diagnosis of white matter and connectivity disorders. The current review provides an overview of the motivation to investigate white matter fMRI activation, as well as the published evidence of this phenomenon. We speculate on possible neurophysiologic bases of white matter fMRI signals, and discuss potential explanations for why reports of white matter fMRI activation are relatively scarce. We end with a discussion of future basic and clinical research directions in the study of white matter fMRI. PMID:25152709

  1. Concise review: reprogramming strategies for cardiovascular regenerative medicine: from induced pluripotent stem cells to direct reprogramming.

    Budniatzky, Inbar; Gepstein, Lior

    2014-04-01

    Myocardial cell-replacement therapies are emerging as novel therapeutic paradigms for myocardial repair but are hampered by the lack of sources of autologous human cardiomyocytes. The recent advances in stem cell biology and in transcription factor-based reprogramming strategies may provide exciting solutions to this problem. In the current review, we describe the different reprogramming strategies that can give rise to cardiomyocytes for regenerative medicine purposes. Initially, we describe induced pluripotent stem cell technology, a method by which adult somatic cells can be reprogrammed to yield pluripotent stem cells that could later be coaxed ex vivo to differentiate into cardiomyocytes. The generated induced pluripotent stem cell-derived cardiomyocytes could then be used for myocardial cell transplantation and tissue engineering strategies. We also describe the more recent direct reprogramming approaches that aim to directly convert the phenotype of one mature cell type (fibroblast) to another (cardiomyocyte) without going through a pluripotent intermediate cell type. The advantages and shortcomings of each strategy for cardiac regeneration are discussed, along with the hurdles that need to be overcome on the road to clinical translation.

  2. Trace-element evidence for the origin of desert varnish by direct aqueous atmospheric deposition

    Thiagarajan, Nivedita; Aeolus Lee, Cin-Ty

    2004-07-01

    Smooth rock surfaces in arid environments are often covered with a thin coating of Fe-Mn oxyhydroxides known as desert varnish. It is debated whether such varnish is formed (a) by slow diagenesis of dust particles deposited on rock surfaces, (b) by leaching from the underlying rock substrate, or (c) by direct deposition of dissolved constituents in the atmosphere. Varnishes collected from smooth rock surfaces in the Mojave Desert and Death Valley, California are shown here to have highly enriched and fractionated trace-element abundances relative to upper continental crust (UCC). They are highly enriched in Co, Ni, Pb and the rare-earth elements (REEs). In particular, they have anomalously high Ce/La and low Y/Ho ratios. These features can only be explained by preferential scavenging of Co, Ni, Pb and the REEs by Fe-Mn oxyhydroxides in an aqueous environment. High field strength elements (HFSEs: Zr, Hf, Ta, Nb, Th), however, show only small enrichments despite the fact that these elements should also be strongly scavenged by Fe-Mn oxyhydroxides. This suggests that their lack of enrichment is a feature inherited from a solution initially poor in HFSEs. The first two scenarios for varnish formation can be ruled out as follows. The high enrichment factors of Fe, Mn and many trace elements cannot be generated by mass loss associated with post-depositional diagenesis of dust particles because such a process predicts only a small increase in concentration. In addition, the highly fractionated abundance patterns of particle reactive element pairs (e.g., Ce/La and Y/Ho) rules out leaching of the rock substrate. This is because if leaching were to occur, varnishes would grow from the inside to the outside, and thus any particle-reactive trace element leached from the substrate would be quantitatively sequestered in the Fe-Mn oxyhydroxide layers, prohibiting any significant elemental fractionations. One remaining possibility is that the Fe, Mn and trace metals in varnish are

  3. New evidence for the origin of intracranial germ cell tumours from primordial germ cells

    Hoei-Hansen, C E; Sehested, A; Juhler, M

    2006-01-01

    that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which...... germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children...... and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected...

  4. Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression.

    Ding, Wei; Nowakowski, Grzegorz S; Knox, Traci R; Boysen, Justin C; Maas, Mary L; Schwager, Susan M; Wu, Wenting; Wellik, Linda E; Dietz, Allan B; Ghosh, Asish K; Secreto, Charla R; Medina, Kay L; Shanafelt, Tait D; Zent, Clive S; Call, Timothy G; Kay, Neil E

    2009-11-01

    It was hypothesized that contact between chronic lymphocytic leukaemia (CLL) B-cells and marrow stromal cells impact both cell types. To test this hypothesis, we utilized a long-term primary culture system from bone biopsies that reliably generates a mesenchymal stem cell (MSC). Co-culture of MSC with CLL B-cells protected the latter from both spontaneous apoptosis and drug-induced apoptosis. The CD38 expression in previously CD38 positive CLL B-cells was up-regulated with MSC co-culture. Upregulation of CD71, CD25, CD69 and CD70 in CLL B-cells was found in the co-culture. CD71 upregulation was more significantly associated with high-risk CLL, implicating CD71 regulation in the microenvironment predicting disease progression. In MSC, rapid ERK and AKT phosphorylation (within 30 min) were detected when CLL B-cells and MSC were separated by transwell; indicating that activation of MSC was mediated by soluble factors. These findings support a bi-directional activation between bone marrow stromal cells and CLL B-cells.

  5. CD4/CD8/Dendritic cell complexes in the spleen: CD8+ T cells can directly bind CD4+ T cells and modulate their response

    Barinov, Aleksandr; Galgano, Alessia; Krenn, Gerald; Tanchot, Corinne; Vasseur, Florence

    2017-01-01

    CD4+ T cell help to CD8+ T cell responses requires that CD4+ and CD8+ T cells interact with the same antigen presenting dendritic cell (Ag+DC), but it remains controversial whether helper signals are delivered indirectly through a licensed DC and/or involve direct CD4+/CD8+ T cell contacts and/or the formation of ternary complexes. We here describe the first in vivo imaging of the intact spleen, aiming to evaluate the first interactions between antigen-specific CD4+, CD8+ T cells and Ag+DCs. We show that in contrast to CD4+ T cells which form transient contacts with Ag+DC, CD8+ T cells form immediate stable contacts and activate the Ag+DC, acquire fragments of the DC membranes by trogocytosis, leading to their acquisition of some of the DC properties. They express MHC class II, and become able to present the specific Marilyn peptide to naïve Marilyn CD4+ T cells, inducing their extensive division. In vivo, these CD8+ T cells form direct stable contacts with motile naïve CD4+ T cells, recruiting them to Ag+DC binding and to the formation of ternary complexes, where CD4+ and CD8+ T cells interact with the DC and with one another. The presence of CD8+ T cells during in vivo immune responses leads to the early activation and up-regulation of multiple functions by CD4+ T lymphocytes. Thus, while CD4+ T cell help is important to CD8+ T cell responses, CD8+ T cells can interact directly with naïve CD4+ T cells impacting their recruitment and differentiation. PMID:28686740

  6. Direct Electron Transfer of Dehydrogenases for Development of 3rd Generation Biosensors and Enzymatic Fuel Cells

    Paolo Bollella

    2018-04-01

    Full Text Available Dehydrogenase based bioelectrocatalysis has been increasingly exploited in recent years in order to develop new bioelectrochemical devices, such as biosensors and biofuel cells, with improved performances. In some cases, dehydrogeases are able to directly exchange electrons with an appropriately designed electrode surface, without the need for an added redox mediator, allowing bioelectrocatalysis based on a direct electron transfer process. In this review we briefly describe the electron transfer mechanism of dehydrogenase enzymes and some of the characteristics required for bioelectrocatalysis reactions via a direct electron transfer mechanism. Special attention is given to cellobiose dehydrogenase and fructose dehydrogenase, which showed efficient direct electron transfer reactions. An overview of the most recent biosensors and biofuel cells based on the two dehydrogenases will be presented. The various strategies to prepare modified electrodes in order to improve the electron transfer properties of the device will be carefully investigated and all analytical parameters will be presented, discussed and compared.

  7. SERCA directs cell migration and branching across species and germ layers

    Danielle V. Bower

    2017-10-01

    Full Text Available Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis and ectoderm (Drosophila nervous system behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding.

  8. A comparative study of approaches to direct methanol fuel cells modelling

    Oliveira, V.B.; Falcao, D.S.; Pinto, A.M.F.R. [Centro de Estudos de Fenomenos de Transporte, Departamento de Eng. Quimica, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Rangel, C.M. [Instituto Nacional de Engenharia, Tecnologia e Inovacao, Paco do Lumiar, 22,1649-038 (Portugal)

    2007-03-15

    Fuel cell modelling has received much attention over the past decade in an attempt to better understand the phenomena occurring within the cell. Mathematical models and simulation are needed as tools for design optimization of fuel cells, stacks and fuel cell power systems. Analytical, semi-empirical and mechanistic models for direct methanol fuel cells (DMFC) are reviewed. Effective models were until now developed describing the fundamental electrochemical and transport phenomena taking place in the cell. More research is required to develop models that can account for the two-phase flows occurring in the anode and cathode of the DMFC. The merits and demerits of the models are presented. Selected models of different categories are implemented and discussed. Finally, one of the selected simplified models is proposed as a computer-aided tool for real-time system level DMFC calculations. (author)

  9. Exploration of molecular pathways mediating electric field-directed Schwann cell migration by RNA-Seq

    Yao, Li; Li, Yongchao; Knapp, Jennifer; Smith, Peter

    2015-01-01

    In peripheral nervous systems, Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. Following spinal cord injury, Schwann cells regenerate and migrate to the lesion and are involved in the spinal cord regeneration process. Transplantation of Schwann cells into injured neural tissue results in enhanced spinal axonal regeneration. Effective directional migration of Schwann cells is critical in the neural regeneration process. In this study, we report that Schwann cells migrate anodally in an applied electric field (EF). The directedness and displacement of anodal migration increased significantly when the strength of the EF increased from 50 mV/mm to 200 mV/mm. The EF did not significantly affect the cell migration speed. To explore the genes and signaling pathways that regulate cell migration in EFs, we performed a comparative analysis of differential gene expression between cells stimulated with an EF (100 mV/mm) and those without using next-generation RNA sequencing, verified by RT-qPCR. Based on the cut-off criteria (FC > 1.2, q cells versus EF-stimulated cells. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that compared to the control group, 21 pathways are down-regulated, while 10 pathways are up-regulated. Differentially expressed genes participate in multiple cellular signaling pathways involved in the regulation of cell migration, including pathways of regulation of actin cytoskeleton, focal adhesion, and PI3K-Akt. PMID:25557037

  10. An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells.

    Lorentzen, Anna; Bamber, Jeffrey; Sadok, Amine; Elson-Schwab, Ilan; Marshall, Christopher J

    2011-04-15

    Melanoma cells can switch between an elongated mesenchymal-type and a rounded amoeboid-type migration mode. The rounded 'amoeboid' form of cell movement is driven by actomyosin contractility resulting in membrane blebbing. Unlike elongated A375 melanoma cells, rounded A375 cells do not display any obvious morphological front-back polarisation, although polarisation is thought to be a prerequisite for cell movement. We show that blebbing A375 cells are polarised, with ezrin (a linker between the plasma membrane and actin cytoskeleton), F-actin, myosin light chain, plasma membrane, phosphatidylinositol (4,5)-bisphosphate and β1-integrin accumulating at the cell rear in a uropod-like structure. This structure does not have the typical protruding shape of classical leukocyte uropods, but, as for those structures, it is regulated by protein kinase C. We show that the ezrin-rich uropod-like structure (ERULS) is an inherent feature of polarised A375 cells and not a consequence of cell migration, and is necessary for cell invasion. Furthermore, we demonstrate that membrane blebbing is reduced at this site, leading to a model in which the rigid ezrin-containing structure determines the direction of a moving cell through localised inhibition of membrane blebbing.

  11. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

    Prabhat S Kunwar

    2003-12-01

    Full Text Available In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR, Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

  12. The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration

    Lena Collenburg

    2017-08-01

    Full Text Available Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.

  13. Cell-patterned glass spray for direct drug assay using mass spectrometry

    Wu, Jing; Wang, Shiqi; Chen, Qiushui; Jiang, Hao; Liang, Shuping; Lin, Jin-Ming

    2015-01-01

    In this work, the establishment of a glass spray mass spectrometry (GS-MS) platform for direct cell-based drug assay was described. Cell co-culture, drug-induced cell apoptosis, proliferation analysis and intracellular drug absorption measurement were performed simultaneously on this specifically designed platform. Two groups of co-cultured cells (NIH-3T3/HepG2 and HepG2/MCF-7) were cultivated and they showed high viability within 3 days. The biocompatibility of the platform facilitated the subsequent bioassays, in which, cyclophosphamide (CPA) and genistein were used as the model drugs. The distinctions of cell apoptosis and proliferation between the mono-cultured and co-cultured cells were clearly observed and well explained by in situ GS-MS measurements. A satisfactory linearity of the calibration curve between the relative MS intensity and CPA concentrations was obtained using stable isotope labeling method (y = 0.16545 + 0.0985x, R"2 = 0.9937). The variations in the quantity of absorbed drug were detected and the results were consistent with the concentration-dependence of cell apoptosis. All the results demonstrated that direct cell-based drug assay could be performed on the stable isotope labeling assisted GS-MS platform in a facile and quantitative manner. - Highlights: • A versatile glass spray mass spectrometry (GS-MS) platform for direct cell-based drug assay was developed in this paper. • It has characteristics of the atmospheric pressure ionization method. • It is multifunctional for cell co-culture, bioassays, qualitative and quantitative intracellular drug absorption measurement. • GS-MS has the potential to increase the use of mass spectrometry in biological analysis.

  14. Performance of direct alcohol fuel cells fed with mixed methanol/ethanol solutions

    Wongyao, N. [The Joint Graduate School of Energy and Environment, King Mongkut' s University of Technology Thonburi, 126 Pracha-Uthit Rd., Bang Mod, Thung Khru, Bangkok 10140 (Thailand); Therdthianwong, A., E-mail: apichai.the@kmutt.ac.t [Fuel Cell and Hydrogen Research and Engineering Center, Clean Energy System Group, PDTI, King Mongkut' s University of Technology Thonburi, 126 Pracha-Uthit Rd., Bang Mod, Thung Khru, Bangkok 10140 (Thailand); Therdthianwong, S. [Department of Chemical Engineering, Faculty of Engineering, King Mongkut' s University of Technology Thonburi, 126 Pracha-Uthit Rd., Bang Mod, Thung Khru, Bangkok 10140 (Thailand)

    2011-07-15

    Research highlights: {yields} We examined the performance of direct alcohol fuel cells fed with mixed alcohol. {yields} PtRu-PtSn/C and PtRu/C as catalysts for mixed alcohol electrooxidation reaction. {yields} Misplace adsorption of ethanol on PtRu/C caused the cell performance drop. {yields} PtRu/C showed higher performance than PtRu-PtSn/C for mixed alcohol fuel. -- Abstract: In combining the advantages of both methanol and ethanol, direct alcohol fuel cells fed with mixed alcohol solutions (1 M methanol and 1 M ethanol in varying volume ratios) were tested for performance. Employing a PtRu-PtSn/C catalyst as anode, cell performance was found to diminish rapidly even at 2.5% by volume ethanol mixture. Further increase of ethanol exceeded 10%, the cell performance gradually decreased and finally approached that of direct ethanol fuel cells. The causes of the decrease in the cell performance were the slow electro-oxidation of ethanol and the misplaced adsorption of ethanol on PtRu/C. By comparing the PtRu-PtSn/C cell with the PtRu/C cell operated with mixed alcohol solutions, the cell using PtRu/C as an anode catalyst provided higher power density since more PtRu/C surface was available for methanol oxidation reaction and less ohmic resistance of PtRu/C than that of PtRu-PtSn/C. In order to reach optimization of DAFC performance fed with mixed alcohol, the electrocatalyst used for the anode must selectively adsorb an alcohol, especially ethanol.

  15. Performance of direct alcohol fuel cells fed with mixed methanol/ethanol solutions

    Wongyao, N.; Therdthianwong, A.; Therdthianwong, S.

    2011-01-01

    Research highlights: → We examined the performance of direct alcohol fuel cells fed with mixed alcohol. → PtRu-PtSn/C and PtRu/C as catalysts for mixed alcohol electrooxidation reaction. → Misplace adsorption of ethanol on PtRu/C caused the cell performance drop. → PtRu/C showed higher performance than PtRu-PtSn/C for mixed alcohol fuel. -- Abstract: In combining the advantages of both methanol and ethanol, direct alcohol fuel cells fed with mixed alcohol solutions (1 M methanol and 1 M ethanol in varying volume ratios) were tested for performance. Employing a PtRu-PtSn/C catalyst as anode, cell performance was found to diminish rapidly even at 2.5% by volume ethanol mixture. Further increase of ethanol exceeded 10%, the cell performance gradually decreased and finally approached that of direct ethanol fuel cells. The causes of the decrease in the cell performance were the slow electro-oxidation of ethanol and the misplaced adsorption of ethanol on PtRu/C. By comparing the PtRu-PtSn/C cell with the PtRu/C cell operated with mixed alcohol solutions, the cell using PtRu/C as an anode catalyst provided higher power density since more PtRu/C surface was available for methanol oxidation reaction and less ohmic resistance of PtRu/C than that of PtRu-PtSn/C. In order to reach optimization of DAFC performance fed with mixed alcohol, the electrocatalyst used for the anode must selectively adsorb an alcohol, especially ethanol.

  16. Thermodynamic analysis of Direct Urea Solid Oxide Fuel Cell in combined heat and power applications

    Abraham, F.; Dincer, I.

    2015-12-01

    This paper presents a comprehensive steady state modelling and thermodynamic analysis of Direct Urea Solid Oxide Fuel Cell integrated with Gas Turbine power cycle (DU-SOFC/GT). The use of urea as direct fuel mitigates public health and safety risks associated with the use of hydrogen and ammonia. The integration scheme in this study covers both oxygen ion-conducting solid oxide fuel cells (SOFC-O) and hydrogen proton-conducting solid oxide fuel cells (SOFC-H). Parametric case studies are carried out to investigate the effects of design and operating parameters on the overall performance of the system. The results reveal that the fuel cell exhibited the highest level of exergy destruction among other system components. Furthermore, the SOFC-O based system offers better overall performance than that with the SOFC-H option mainly due to the detrimental reverse water-gas shift reaction at the SOFC anode as well as the unique configuration of the system.

  17. A synthetic glycan microarray enables epitope mapping of plant cell wall glycan-directed antibodies

    Ruprecht, Colin; Bartetzko, Max P; Senf, Deborah

    2017-01-01

    In the last three decades, more than 200 monoclonal antibodies have been raised against most classes of plant cell wall polysaccharides by different laboratories world-wide. These antibodies are widely used to identify differences in plant cell wall components in mutants, organ and tissue types......, and developmental stages. Despite their importance and broad use, the precise binding epitope for only a few of these antibodies has been determined. Here, we use a plant glycan microarray equipped with 88 synthetic oligosaccharides to comprehensively map the epitopes of plant cell wall glycan-directed antibodies....... Our results reveal the binding epitopes for 78 arabinogalactan-, rhamnogalacturonan-, xylan-, and xyloglucan-directed antibodies. We demonstrate that, with knowledge of the exact epitopes recognized by individual antibodies, specific glycosyl hydrolases can be implemented into immunological cell wall...

  18. A flexible thermoresponsive cell culture substrate for direct transfer of keratinocyte cell sheets.

    Praveen, Wulligundam; Madathil, Bernadette K; Sajin Raj, R S; Kumary, T V; Anil Kumar, P R

    2017-10-25

    Most cell sheet engineering systems require a support or carrier to handle the harvested cell sheets. In this study, polyethylene terephthalate-based overhead projection transparency sheets (OHPS) were subjected to surface hydrolysis by alkali treatment to increase pliability and hydrophilicity and enable poly(N-isopropylacrylamide-co-glycidylmethacrylate) copolymer (NGMA) coating to impart thermoresponsiveness. NGMA was applied on the modified OHPS by the technique of spin coating using an indigenously designed spin coater. The spin coating had the advantage of using low volumes of the polymer and a reduced coating time. The surface chemistry and thermoresponsive coating was analyzed by Fourier transform infrared spectroscopy and water contact angle. Human keratinocyte cells were cultured on the spin coated surface and scaffold-free cell sheets were successfully harvested by simple variation of temperature. These cell sheets were found to be viable, exhibited epithelial characteristic and cell-cell contact as confirmed by positive immunostaining for ZO-1. The integrity and morphology of the cell sheet was confirmed by stereomicroscopy and E-SEM. These results highlight the potential of the NGMA spin coated modified OHPS to serve as a thermoresponsive culture surface-cum-flexible transfer tool.

  19. A direct and at nanometer scale study of electrical charge distribution on membranes of alive cells

    Marlière Christian

    2016-01-01

    Full Text Available In this paper is presented an innovative method to map in-vivo and at nanometer scale the electrical charge distribution on membranes of alive cells. It relies on a new atomic force microscopy (AFM mode based on an electro-mechanical coupling effect. Furthermore, an additional electrical signal detected by both the deflection of the AFM cantilever and simultaneous direct current measurements was detected at low scanning rates. It was attributed to the detection of the current stemming from ionic channels. It opens a new way to directly investigate in situ biological electrical surface processes involved in bacterial adhesion, biofilm formation, microbial fuel cells, etc.

  20. Low-Pt-Content Anode Catalyst for Direct Methanol Fuel Cells

    Narayanan, Sekharipuram; Whitacre, Jay

    2008-01-01

    Combinatorial experiments have led to the discovery that a nanophase alloy of Pt, Ru, Ni, and Zr is effective as an anode catalyst material for direct methanol fuel cells. This discovery has practical significance in that the electronic current densities achievable by use of this alloy are comparable or larger than those obtained by use of prior Pt/Ru catalyst alloys containing greater amounts of Pt. Heretofore, the high cost of Pt has impeded the commercialization of direct methanol fuel cells. By making it possible to obtain a given level of performance at reduced Pt content (and, hence, lower cost), the discovery may lead to reduction of the economic impediment to commercialization.

  1. Hydroxide Self-Feeding High-Temperature Alkaline Direct Formate Fuel Cells.

    Li, Yinshi; Sun, Xianda; Feng, Ying

    2017-05-22

    Conventionally, both the thermal degradation of the anion-exchange membrane and the requirement of additional hydroxide for fuel oxidation reaction hinder the development of the high-temperature alkaline direct liquid fuel cells. The present work addresses these two issues by reporting a polybenzimidazole-membrane-based direct formate fuel cell (DFFC). Theoretically, the cell voltage of the high-temperature alkaline DFFC can be as high as 1.45 V at 90 °C. It has been demonstrated that a proof-of-concept alkaline DFFC without adding additional hydroxide yields a peak power density of 20.9 mW cm -2 , an order of magnitude higher than both alkaline direct ethanol fuel cells and alkaline direct methanol fuel cells, mainly because the hydrolysis of formate provides enough OH - ions for formate oxidation reaction. It was also found that this hydroxide self-feeding high-temperature alkaline DFFC shows a stable 100 min constant-current discharge at 90 °C, proving the conceptual feasibility. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

    Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

    2015-07-01

    Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

  3. Direct-write Bioprinting of Cell-laden Methacrylated Gelatin Hydrogels

    Bertassoni, Luiz E.; Cardoso, Juliana C.; Manoharan, Vijayan; Cristino, Ana L.; Bhise, Nupura S.; Araujo, Wesleyan A.; Zorlutuna, Pinar; Vrana, Nihal E.; Ghaemmaghami, Amir M.

    2014-01-01

    Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least 8 days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. PMID:24695367

  4. Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels

    Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Dokmeci, Mehmet R; Khademhosseini, Ali; Ghaemmaghami, Amir M

    2014-01-01

    Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. (paper)

  5. Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels.

    Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Ghaemmaghami, Amir M; Dokmeci, Mehmet R; Khademhosseini, Ali

    2014-06-01

    Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms.

  6. Direct microculture enzyme-linked immunosorbent assay for studying neural cells: oligodendrocytes.

    Gard, A L; Warrington, A E; Pfeiffer, S E

    1988-05-01

    Oligodendrocyte development has been studied in a standardized primary microculture system initiated from day 20-21 fetal rat brain using a solid-phase enzyme-linked immunosorbent assay (ELISA) carried out directly on fixed cells (direct microculture ELISA). A highly reproducible dissociation procedure is described that allows careful control of the number of cells seeded per culture. At a seeding density of 1 x 10(5) cells/culture, up to 250 oligodendrocyte-generating microcultures consisting of 10-12% oligodendrocytes can be prepared from a single fetal rat brain, thereby permitting the simultaneous assay of multiple developmental parameters in sibling cultures. The validity of this method for quantifying myelinogenesis was established by comparing the results obtained by direct microculture ELISA with immunocytochemical counting of cells in parallel cultures. As few as 200 oligodendrocytes could be detected using a biotinylated anti-Ig and an avidin-urease conjugate detection system; CNP immunoreactivity measured by ELISA was linearly proportional to the number of immunolabeled cells between 6 and 34 days in culture; the developmental time courses of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and myelin basic protein (MBP) expression determined by the two methods were very similar. Finally, cell suspensions were seeded at increasing dilution to determine the number of cells required to generate cultures that tested positive for oligodendrocytes by ELISA. As few as 9,000 cells were sufficient, predicting a minimum of 8,000 oligoprogenitors per 20-21 day fetal rat brain. The application of direct microculture ELISA for studying oligodendrocyte population size and myelinogenesis is discussed.

  7. On the Use of Potential Denaturing Agents for Ethanol in Direct Ethanol Fuel Cells

    Domnik Bayer; Florina Jung; Birgit Kintzel; Martin Joos; Carsten Cremers; Dierk Martin; Jörg Bernard; Jens Tübke

    2011-01-01

    Acidic or alkaline direct ethanol fuel cells (DEFCs) can be a sustainable alternative for power generation if they are fuelled with bio-ethanol. However, in order to keep the fuel cheap, ethanol has to be exempted from tax on spirits by denaturing. In this investigation the potential denaturing agents fusel oil, tert-butyl ethyl ether, and Bitrex were tested with regard to their compatibility with fuel cells. Experiments were carried out both in sulphuric acid and potassium hydroxide solution...

  8. Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.

    Hao Ren

    Full Text Available Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons. The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.

  9. Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.

    Ren, Hao; Liu, Ning-Yu; Andreasen, Arne; Thomsen, Jesper S; Cao, Liu; Christensen, Erik I; Zhai, Xiao-Yue

    2013-01-01

    Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons). The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.

  10. Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC.

    Cyntia F Montenegro

    Full Text Available The connective tissue formed by extracellular matrix (ECM rich in fibronectin and collagen consists a barrier that cancer cells have to overpass to reach blood vessels and then a metastatic site. Cell adhesion to fibronectin is mediated by αvβ3 and α5β1 integrins through an RGD motif present in this ECM protein, thus making these receptors key targets for cell migration studies. Here we investigated the effect of an RGD disintegrin, DisBa-01, on the migration of human fibroblasts (BJ and oral squamous cancer cells (OSCC, SCC25 on a fibronectin-rich environment. Time-lapse images were acquired on fibronectin-coated glass-bottomed dishes. Migration speed and directionality analysis indicated that OSCC cells, but not fibroblasts, showed significant decrease in both parameters in the presence of DisBa-01 (1μM and 2μM. Integrin expression levels of the α5, αv and β3 subunits were similar in both cell lines, while β1 subunit is present in lower levels on the cancer cells. Next, we examined whether the effects of DisBa-01 were related to changes in adhesion properties by using paxillin immunostaining and total internal reflection fluorescence TIRF microscopy. OSCCs in the presence of DisBa-01 showed increased adhesion sizes and number of maturing adhesion. The same parameters were analyzed usingβ3-GFP overexpressing cells and showed that β3 overexpression restored cell migration velocity and the number of maturing adhesion that were altered by DisBa-01. Surface plasmon resonance analysis showed that DisBa-01 has 100x higher affinity for αvβ3 integrin than forα5β1 integrin. In conclusion, our results suggest that the αvβ3 integrin is the main receptor involved in cell directionality and its blockage may be an interesting alternative against metastasis.

  11. Evidence Supporting Intralesional Stem Cell Therapy to Improve Equine Flexor Tendon Healing

    Sushmitha Durgam

    2017-01-01

    Full Text Available Clinical bottom lineCurrent experimental evidence suggests that intralesional stem cell administration improves the histological characteristics and matrix organisation of healing equine superficial digital flexor tendons (SDFT; however, the clinical relevance of these findings are not clear. Current case-based evidence suggests that cell-based therapies improve the quality of tendon healing and reduce the recurrence rates of SDFT injuries but the lack of any randomised, controlled prospective studies with function-based outcomes is still concerning, given the widespread advocacy for and use of ‘stem cell’ therapies for the treatment of equine tendon injuries. 

  12. Mycobacterium tuberculosis directs T helper 2 cell differentiation by inducing interleukin-1β production in dendritic cells.

    Dwivedi, Ved Prakash; Bhattacharya, Debapriya; Chatterjee, Samit; Prasad, Durbaka Vijay Raghva; Chattopadhyay, Debprasad; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

    2012-09-28

    Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), resides and replicates within phagocytes and persists in susceptible hosts by modulating protective innate immune responses. Furthermore, M. tuberculosis promotes T helper 2 (Th2) immune responses by altering the balance of T cell polarizing cytokines in infected cells. However, cytokines that regulate Th2 cell differentiation during TB infection remain unknown. Here we show that IL-1β, produced by phagocytes infected by virulent M. tuberculosis strain H37Rv, directs Th2 cell differentiation. In sharp contrast, the vaccine strain bacille Calmette-Guérin as well as RD-1 and ESAT-6 mutants of H37Rv failed to induce IL-1β and promote Th2 cell differentiation. Furthermore, ESAT-6 induced IL-1β production in dendritic cells (DCs), and CD4(+) T cells co-cultured with infected DCs differentiated into Th2 cells. Taken together, our findings indicate that IL-1β induced by RD-1/ESAT-6 plays an important role in the differentiation of Th2 cells, which in turn facilitates progression of TB by inhibiting host protective Th1 responses.

  13. Performance comparison of low-temperature direct alcohol fuel cells with different anode catalysts

    Zhou, W. J.; Zhou, B.; Li, W. Z.; Zhou, Z. H.; Song, S. Q.; Sun, G. Q.; Xin, Q.; Douvartzides, S.; Goula, M.; Tsiakaras, P.

    Low-temperature polymer electrolyte membrane fuel cells directly fed by methanol and ethanol were investigated employing carbon supported Pt, PtSn and PtRu as anode catalysts, respectively. Employing Pt/C as anode catalyst, both direct methanol fuel cell (DMFC) and direct ethanol fuel cell (DEFC) showed poor performances even in presence of high Pt loading on anode. It was found that the addition of Ru or Sn to the Pt dramatically enhances the electro-oxidation of both methanol and ethanol. It was also found that the single cell adopting PtRu/C as anode shows better DMFC performance, while PtSn/C catalyst shows better DEFC performance. The single fuel cell using PtSn/C as anode catalyst at 90 °C shows similar power densities whenever fueled by methanol or ethanol. The cyclic voltammetry (CV) and single fuel cell tests indicated that PtRu is more suitable for DMFC while PtSn is more suitable for DEFC.

  14. High-content analysis of single cells directly assembled on CMOS sensor based on color imaging.

    Tanaka, Tsuyoshi; Saeki, Tatsuya; Sunaga, Yoshihiko; Matsunaga, Tadashi

    2010-12-15

    A complementary metal oxide semiconductor (CMOS) image sensor was applied to high-content analysis of single cells which were assembled closely or directly onto the CMOS sensor surface. The direct assembling of cell groups on CMOS sensor surface allows large-field (6.66 mm×5.32 mm in entire active area of CMOS sensor) imaging within a second. Trypan blue-stained and non-stained cells in the same field area on the CMOS sensor were successfully distinguished as white- and blue-colored images under white LED light irradiation. Furthermore, the chemiluminescent signals of each cell were successfully visualized as blue-colored images on CMOS sensor only when HeLa cells were placed directly on the micro-lens array of the CMOS sensor. Our proposed approach will be a promising technique for real-time and high-content analysis of single cells in a large-field area based on color imaging. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue.

    Sinha, Mithun; Sen, Chandan K; Singh, Kanhaiya; Das, Amitava; Ghatak, Subhadip; Rhea, Brian; Blackstone, Britani; Powell, Heather M; Khanna, Savita; Roy, Sashwati

    2018-03-05

    Inflammation, following injury, induces cellular plasticity as an inherent component of physiological tissue repair. The dominant fate of wound macrophages is unclear and debated. Here we show that two-thirds of all granulation tissue fibroblasts, otherwise known to be of mesenchymal origin, are derived from myeloid cells which are likely to be wound macrophages. Conversion of myeloid to fibroblast-like cells is impaired in diabetic wounds. In cross-talk between keratinocytes and myeloid cells, miR-21 packaged in extracellular vesicles (EV) is required for cell conversion. EV from wound fluid of healing chronic wound patients is rich in miR-21 and causes cell conversion more effectively compared to that by fluid from non-healing patients. Impaired conversion in diabetic wound tissue is rescued by targeted nanoparticle-based delivery of miR-21 to macrophages. This work introduces a paradigm wherein myeloid cells are recognized as a major source of fibroblast-like cells in the granulation tissue.

  16. A ROLE FOR INTERLEUKIN 8 IN DIRECT REGULATION OF T CELL FUNCTIONAL ACTIVITY

    M. E. Meniailo

    2017-01-01

    Full Text Available CD3+T lymphocytes were isolated from normal donors by positive magnetic separation. Activation of the T cells with particles conjugated with antibodies to CD3, СD28 and СD2 molecules led to substantial increase in T cell production of interleukin-8 (IL-8. An interleukin-8 receptor (CXCR1, CD181 was initially expressed in 13.3% of T lymphocytes. Activation of T lymphocytes resulted into a detectable increase of CD181+ cell number among CD4+ naïve cells and CD4+ terminally-differentiated effector cells, and, conversely, into decrease of their number among CD4+ effector memory cells. Activation of T lymphocytes was assessed by membrane expression of CD25 molecule (receptor for IL-2. IL-8 (0.01-10.0 ng/ml was shown to markedly reduce activation of both CD4- and CD4+ effector memory T cells, as well as terminallydifferentiated T effectors, without significantly affecting activation of naive T lymphocytes and central memory T cells. IL-8 noticeably increased IL-2 production by activated Т cells, caused a reduced IL-10 production, and did not significantly affect the secretion of IFNγ and IL-4. The data obtained suggest a significance of IL-8 for direct regulation of adaptive T cell responses.

  17. Homology-Directed Recombination for Enhanced Engineering of Chimeric Antigen Receptor T Cells

    Malika Hale

    2017-03-01

    Full Text Available Gene editing by homology-directed recombination (HDR can be used to couple delivery of a therapeutic gene cassette with targeted genomic modifications to generate engineered human T cells with clinically useful profiles. Here, we explore the functionality of therapeutic cassettes delivered by these means and test the flexibility of this approach to clinically relevant alleles. Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR T cells could be used to treat patients with HIV-associated B cell malignancies. We show that targeted delivery of an anti-CD19 CAR cassette to the CCR5 locus using a recombinant AAV homology template and an engineered megaTAL nuclease results in T cells that are functionally equivalent, in both in vitro and in vivo tumor models, to CAR T cells generated by random integration using lentiviral delivery. With the goal of developing off-the-shelf CAR T cell therapies, we next targeted CARs to the T cell receptor alpha constant (TRAC locus by HDR, producing TCR-negative anti-CD19 CAR and anti-B cell maturation antigen (BCMA CAR T cells. These novel cell products exhibited in vitro cytolytic activity against both tumor cell lines and primary cell targets. Our combined results indicate that high-efficiency HDR delivery of therapeutic genes may provide a flexible and robust method that can extend the clinical utility of cell therapeutics.

  18. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the

  19. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

    Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

    2006-09-01

    Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

  20. CD4+ T cell-derived novel peptide Thp5 induces interleukin-4 production in CD4+ T cells to direct T helper 2 cell differentiation.

    Khan, Mohd Moin; Chatterjee, Samit; Dwivedi, Ved Prakash; Pandey, Nishant Kumar; Singh, Yogesh; Tousif, Sultan; Bhavesh, Neel Sarovar; Van Kaer, Luc; Das, Jyoti; Das, Gobardhan

    2012-01-20

    The differentiation of naïve CD4(+) T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4(+) T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4(+) T cells. Induction of IL-4 in CD4(+) T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-β) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4(+) T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype.

  1. A Self-Supported Direct Borohydride-Hydrogen Peroxide Fuel Cell System

    Ashok K. Shukla

    2009-04-01

    Full Text Available A self-supported direct borohydride-hydrogen peroxide fuel cell system with internal manifolds and an auxiliary control unit is reported. The system, while operating under ambient conditions, delivers a peak power of 40 W with about 2 W to run the auxiliary control unit. A critical cause and effect analysis, on the data for single cells and stack, suggests the optimum concentrations of fuel and oxidant to be 8 wt. % NaBH4 and 2 M H2O2, respectively in extending the operating time of the system. Such a fuel cell system is ideally suited for submersible and aerospace applications where anaerobic conditions prevail.

  2. A quasi-direct methanol fuel cell system based on blend polymer membrane electrolytes

    Li, Qingfeng; Hjuler, Hans Aage; Hasiotis, C.

    2002-01-01

    , compared to less than 100 ppm CO for the Nafion-based technology at 80degrees C. The high CO tolerance makes it possible to use the reformed hydrogen directly from a simple methanol reformer without further CO removal. That both the fuel cell and the methanol reformer operate at temperatures around 200......On the basis of blend polymer electrolytes of polybenzimidazole and sulfonated polysulfone, a polymer electrolyte membrane fuel cell was developed with an operational temperature up to 200degrees C. Due to the high operational temperature, the fuel cell can tolerate 1.0-3.0 vol % CO in the fuel...

  3. A critical examination of the numerology of antigen-binding cells: evidence for multiple receptor specificities on single cells.

    Miller, A

    1977-01-01

    The data available from other laboratories as well as our own on the frequency of cells recognizing major histocompatibility antigens or conventional protein and hapten antigens is critically evaluated. The frequency of specific binding for a large number of antigens is sufficiently high to support the idea that at least part of the antigen-binding cell populati