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Sample records for high self-renewal capacity

  1. CrxOS maintains the self-renewal capacity of murine embryonic stem cells

    International Nuclear Information System (INIS)

    Saito, Ryota; Yamasaki, Tokiwa; Nagai, Yoko; Wu, Jinzhan; Kajiho, Hiroaki; Yokoi, Tadashi; Noda, Eiichiro; Nishina, Sachiko; Niwa, Hitoshi; Azuma, Noriyuki; Katada, Toshiaki; Nishina, Hiroshi

    2009-01-01

    Embryonic stem (ES) cells maintain pluripotency by self-renewal. Several homeoproteins, including Oct3/4 and Nanog, are known to be key factors in maintaining the self-renewal capacity of ES cells. However, other genes required for the mechanisms underlying this process are still unclear. Here we report the identification by in silico analysis of a homeobox-containing gene, CrxOS, that is specifically expressed in murine ES cells and is essential for their self-renewal. ES cells mainly express the short isoform of endogenous CrxOS. Using a polyoma-based episomal expression system, we demonstrate that overexpression of the CrxOS short isoform is sufficient for maintaining the undifferentiated morphology of ES cells and stimulating their proliferation. Finally, using RNA interference, we show that CrxOS is essential for the self-renewal of ES cells, and provisionally identify foxD3 as a downstream target gene of CrxOS. To our knowledge, ours is the first delineation of the physiological role of CrxOS in ES cells.

  2. ERK2 suppresses self-renewal capacity of embryonic stem cells, but is not required for multi-lineage commitment.

    Directory of Open Access Journals (Sweden)

    William B Hamilton

    Full Text Available Activation of the FGF-ERK pathway is necessary for naïve mouse embryonic stem (ES cells to exit self-renewal and commit to early differentiated lineages. Here we show that genetic ablation of Erk2, the predominant ERK isozyme expressed in ES cells, results in hyper-phosphorylation of ERK1, but an overall decrease in total ERK activity as judged by substrate phosphorylation and immediate-early gene (IEG induction. Normal induction of this subset of canonical ERK targets, as well as p90RSK phosphorylation, was rescued by transgenic expression of either ERK1 or ERK2 indicating a degree of functional redundancy. In contrast to previously published work, Erk2-null ES cells exhibited no detectable defect in lineage specification to any of the three germ layers when induced to differentiate in either embryoid bodies or in defined neural induction conditions. However, under self-renewing conditions Erk2-null ES cells express increased levels of the pluripotency-associated transcripts, Nanog and Tbx3, a decrease in Nanog-GFP heterogeneity, and exhibit enhanced self-renewal in colony forming assays. Transgenic add-back of ERK2 is capable of restoring normal pluripotent gene expression and self-renewal capacity. We show that ERK2 contributes to the destabilization of ES cell self-renewal by reducing expression of pluripotency genes, such as Nanog, but is not specifically required for the early stages of germ layer specification.

  3. Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche.

    Science.gov (United States)

    Vanegas, Natalia-Del Pilar; Vernot, Jean-Paul

    2017-01-01

    Leukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells. A leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line. After 3 days, the REH-conditioned medium was removed and freshly isolated CD34+ at a density of up to 100,000 cells/ml were added to the leukemic niche. CD34+ cell evaluations (cell cycle, self-renewal gene expression and migration capacity) were performed after 3 further days of co-culture. Additionally, we preliminary investigated the soluble factors present in the leukemic niche and their effect on the mesenchymal stem cells. Statistical significance was assessed by Student's t test or the nonparametric test Kolmogorov-Smirnov. By co-culturing normal mesenchymal stem cells with the REH-conditioned medium we showed that hematopoietic stem cells, normally in a quiescent state, enter cell cycle and proliferate. This loss of quiescence was accompanied by an increased expression of Ki-67 and c-Myc, two well-known cell proliferation-associated markers. Two central regulators of quiescence GATA2 and p53 were also down regulated. Importantly, two genes involved in HSC self-renewal, Klf4 and the histone-lysine N -methyltransferase enzyme Ezh2, were severely affected. On the contrary, c-Kit expression, the stem cell factor receptor, was upregulated in hematopoietic stem cells when compared to the normal niche. Interestingly, mesenchymal stem cells incubated with the REH-conditioned medium stopped growing, showed a flattened morphology with the appearance of small vacuoles, and importantly, became positive for the senescence-associated beta-galactosidase activity. Evaluation of the leukemic

  4. Aldo Leopold's land health from a resilience point of view: self-renewal capacity of social-ecological systems.

    Science.gov (United States)

    Berkes, Fikret; Doubleday, Nancy C; Cumming, Graeme S

    2012-09-01

    Health approaches to ecology have a strong basis in Aldo Leopold's thinking, and contemporary ecohealth in turn has a strong philosophical basis in Leopold. To commemorate the 125th anniversary of Leopold's birth (1887-1948), we revisit his ideas, specifically the notions of stewardship (land ethic), productive use of ecosystems (land), and ecosystem renewal. We focus on Leopold's perspective on the self-renewal capacity of the land, as understood in terms of integrity and land health, from the contemporary perspective of resilience theory and ecological theory more generally. Using a broad range of literature, we explore insights and implications of Leopold's work for today's human-environment relationships (integrated social-ecological systems), concerns for biodiversity, the development of agency with respect to stewardship, and key challenges of his time and of ours. Leopold's seminal concept of land health can be seen as a triangulation of productive use, self-renewal, and stewardship, and it can be reinterpreted through the resilience lens as the health of social-ecological systems. In contemporary language, this involves the maintenance of biodiversity and ecosystem services, and the ability to exercise agency both for conservation and for environmental justice.

  5. Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.

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    Thomas, Kelsey A; Gibbons, Michael C; Lane, John G; Singh, Anshuman; Ward, Samuel R; Engler, Adam J

    2017-08-01

    Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1816-1823, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. On the self-renewal of teachers.

    Science.gov (United States)

    Waters, David J; Waters, Lane S

    2011-01-01

    In previous issues of the Journal of Veterinary Medical Education, wide-ranging insights on how to achieve excellence in the classroom have been framed by award-winning teachers. These recipes for educational success, however, invariably lack a key ingredient-the teacher's process of self-renewal. What skills and attitudes prime the teacher for continued high performance? To stay out of the ruts of expertise, where does the teacher turn? Teachers and administrators alike recognize its great importance, yet few opportunities for the renewal of teachers are built into the educational system. In this article, we challenge teachers to see their own self-renewal as an underutilized approach to innovate education. We propose a schema for sustained self-renewal: each educator developing her own personalized, hand-picked gallery of intellectual heroes who in turn serve as the educator's life-long teachers. To illustrate the value of this activity, we introduce our own collection of 10 gifted thinkers, providing a brief encounter with each sage as a way of stimulating new thinking on the skills and attitudes that promote personal growth and transformative teaching. We conclude that the veterinary profession should work to create better opportunities for the self-renewal of teachers. By envisioning even our best teachers as unfinished and under construction, we open up a new dialogue situating the self-renewal of teachers at the very core of educational excellence.

  7. Human mesenchymal stem cells self-renew and differentiate according to a deterministic hierarchy.

    Directory of Open Access Journals (Sweden)

    Rahul Sarugaser

    Full Text Available BACKGROUND: Mesenchymal progenitor cells (MPCs have been isolated from a variety of connective tissues, and are commonly called "mesenchymal stem cells" (MSCs. A stem cell is defined as having robust clonal self-renewal and multilineage differentiation potential. Accordingly, the term "MSC" has been criticised, as there is little data demonstrating self-renewal of definitive single-cell-derived (SCD clonal populations from a mesenchymal cell source. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that a tractable MPC population, human umbilical cord perivascular cells (HUCPVCs, was capable of multilineage differentiation in vitro and, more importantly, contributed to rapid connective tissue healing in vivo by producing bone, cartilage and fibrous stroma. Furthermore, HUCPVCs exhibit a high clonogenic frequency, allowing us to isolate definitive SCD parent and daughter clones from mixed gender suspensions as determined by Y-chromosome fluorescent in situ hybridization. CONCLUSIONS/SIGNIFICANCE: Analysis of the multilineage differentiation capacity of SCD parent clones and daughter clones enabled us to formulate a new hierarchical schema for MSC self-renewal and differentiation in which a self-renewing multipotent MSC gives rise to more restricted self-renewing progenitors that gradually lose differentiation potential until a state of complete restriction to the fibroblast is reached.

  8. High molecular weight FGF2 isoforms demonstrate canonical receptor-mediated activity and support human embryonic stem cell self-renewal

    Directory of Open Access Journals (Sweden)

    Denis Kole

    2017-05-01

    Full Text Available Basic fibroblast growth factor (FGF2 is a highly pleiotropic member of a large family of growth factors with a broad range of activities, including mitogenesis and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006, and it is known to be essential for maintenance of balance between survival, proliferation, and self-renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon et al., 2011. A single FGF2 transcript can be translated into five FGF2 protein isoforms, an 18 kDa low molecular weight (LMW isoform and four larger high molecular weight (HMW isoforms (Arese et al., 1999; Arnaud et al., 1999. As they are not generally secreted, high molecular weight (HMW FGF2 isoforms have predominantly been investigated intracellularly; only a very limited number of studies have investigated their activity as extracellular factors. Here we report over-expression, isolation, and biological activity of all recombinant human FGF2 isoforms. We show that HMW FGF2 isoforms can support self-renewal of human embryonic stem cells (hESCs in vitro. Exogenous supplementation with HMW FGF2 isoforms also activates the canonical FGFR/MAPK pathway and induces mitogenic activity in a manner similar to that of the 18 kDa FGF2 isoform. Though all HMW isoforms, when supplemented exogenously, are able to recapitulate LMW FGF2 activity to some degree, it appears that certain isoforms tend to do so more poorly, demonstrating a lesser functional response by several measures. A better understanding of isoform-specific FGF2 effects will lead to a better understanding of developmental and pathological FGF2 signaling.

  9. High-resolution molecular validation of self-renewal and spontaneous differentiation in adipose-tissue derived human mesenchymal stem cells cultured in human platelet lysate

    Science.gov (United States)

    Dudakovic, Amel Dudakovic; Camilleri, Emily; Riester, Scott M.; Lewallen, Eric A.; Kvasha, Sergiy; Chen, Xiaoyue; Radel, Darcie J.; Anderson, Jarett M.; Nair, Asha A.; Evans, Jared M.; Krych, Aaron J.; Smith, Jay; Deyle, David R.; Stein, Janet L.; Stein, Gary S.; Im, Hee-Jeong; Cool, Simon M.; Westendorf, Jennifer J.; Kakar, Sanjeev; Dietz, Allan B.; van Wijnen, Andre J.

    2014-01-01

    Improving the effectiveness of adipose-tissue derived human mesenchymal stromal/stem cells (AMSCs) for skeletal therapies requires a detailed characterization of mechanisms supporting cell proliferation and multi-potency. We investigated the molecular phenotype of AMSCs that were either actively proliferating in platelet lysate or in a basal non-proliferative state. Flow cytometry combined with high-throughput RNA sequencing (RNASeq) and RT-qPCR analyses validate that AMSCs express classic mesenchymal cell surface markers (e.g., CD44, CD73/NT5E, CD90/THY1 and CD105/ENG). Expression of CD90 is selectively elevated at confluence. Self-renewing AMSCs express a standard cell cycle program that successively mediates DNA replication, chromatin packaging, cyto-architectural enlargement and mitotic division. Confluent AMSCs preferentially express genes involved in extracellular matrix (ECM) formation and cellular communication. For example, cell cycle-related biomarkers (e.g., cyclins E2 and B2, transcription factor E2F1) and histone-related genes (e.g., H4, HINFP, NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly upregulated (>10 fold) in quiescent AMSCs. AMSCs also express pluripotency genes (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2) consistent with their multipotent phenotype. Strikingly, AMSCs modulate expression of WNT signaling components and switch production of WNT ligands (from WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while up-regulating WNT-related genes (WISP2, SFRP2 and SFRP4). Furthermore, post-proliferative AMSCs spontaneously express fibroblastic, osteogenic, chondrogenic and adipogenic biomarkers when maintained in confluent cultures. Our findings validate the biological properties of self-renewing and multi-potent AMSCs by providing high-resolution quality control data that support their clinical versatility. PMID:24905804

  10. Hmga2 regulates self-renewal of retinal progenitors.

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    Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

    2014-11-01

    In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

  11. Bmi-1 Regulates Extensive Erythroid Self-Renewal

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    Ah Ram Kim

    2015-06-01

    Full Text Available Red blood cells (RBCs, responsible for oxygen delivery and carbon dioxide exchange, are essential for our well-being. Alternative RBC sources are needed to meet the increased demand for RBC transfusions projected to occur as our population ages. We previously have discovered that erythroblasts derived from the early mouse embryo can self-renew extensively ex vivo for many months. To better understand the mechanisms regulating extensive erythroid self-renewal, global gene expression data sets from self-renewing and differentiating erythroblasts were analyzed and revealed the differential expression of Bmi-1. Bmi-1 overexpression conferred extensive self-renewal capacity upon adult bone-marrow-derived self-renewing erythroblasts, which normally have limited proliferative potential. Importantly, Bmi-1 transduction did not interfere with the ability of extensively self-renewing erythroblasts (ESREs to terminally mature either in vitro or in vivo. Bmi-1-induced ESREs can serve to generate in vitro models of erythroid-intrinsic disorders and ultimately may serve as a source of cultured RBCs for transfusion therapy.

  12. REST controls self-renewal and tumorigenic competence of human glioblastoma cells.

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    Luciano Conti

    Full Text Available The Repressor Element 1 Silencing Transcription factor (REST/NRSF is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets.

  13. LncMAPK6 drives MAPK6 expression and liver TIC self-renewal.

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    Huang, Guanqun; Jiang, Hui; He, Yueming; Lin, Ye; Xia, Wuzheng; Luo, Yuanwei; Liang, Min; Shi, Boyun; Zhou, Xinke; Jian, Zhixiang

    2018-05-15

    Liver tumor initiating cells (TICs) have self-renewal and differentiate capacities, and largely contribute to tumor initiation, metastasis and drug resistance. MAPK signaling is a critical pathway in many biological processes, while its role in liver TICs hasn't been explored. Online-available dataset was used for unbiased screening. Liver TICs were examined CD133 FACS or oncosphere formation. TIC self-renewal was detected by oncosphere formation and tumor initiation assay. LncRNA function was detected by loss of function or gain of function assays. The molecular mechanism of lncRNA was explored by RNA pulldown, RNA immunoprecipitation, ChIP, western blot and double FISH. Here, we examined the expression profiles of MAPK components (MAPKs, MAP2Ks, MAP3Ks, MAP4Ks), and found MAPK6 is most highly expressed in liver cancer samples. Moreover, a divergent lncRNA (long noncoding RNA) of MAPK6, termed lncMAPK6 here, is also overexpressed along with liver tumorigenesis. LncMAPK6 promotes liver tumor propagation and TIC self-renewal through MAPK6. LncMAPK6 interacts with and recruits RNA polymerase II to MAPK6 promoter, and finally activates the transcription of MAPK6. Through MAPK6 transcriptional regulation, lncMAPK6 drives MARK signaling activation. LncMAPK6-MAPK6 pathway can be used for liver TIC targeting. Altogether, lncMAPK6 promotes MARK signaling and the self-renewal of liver TICs through MAPK6 expression. MAPK6 was the most highly expressed MAPK component in liver cancer and liver TICs and lncMAPK6 participated in the transcriptional regulation of MAPK6in cis. This work revealed the importance role of MAPK signaling in liver TIC self-renewal and added a new layer for liver TIC and MAPK6 expression regulation.

  14. Satellite Cell Self-Renewal.

    Science.gov (United States)

    Giordani, Lorenzo; Parisi, Alice; Le Grand, Fabien

    2018-01-01

    Adult skeletal muscle is endowed with regenerative potential through partially recapitulating the embryonic developmental program. Upon acute injury or in pathological conditions, quiescent muscle-resident stem cells, called satellite cells, become activated and give rise to myogenic progenitors that massively proliferate, differentiate, and fuse to form new myofibers and restore tissue functionality. In addition, a proportion of activated cells returns back to quiescence and replenish the pool of satellite cells in order to maintain the ability of skeletal muscle tissue to repair. Self-renewal is the process by which stem cells divide to make more stem cells to maintain the stem cell population throughout life. This process is controlled by cell-intrinsic transcription factors regulated by cell-extrinsic signals from the niche and the microenvironment. This chapter provides an overview about the general aspects of satellite cell biology and focuses on the cellular and molecular aspects of satellite cell self-renewal. To date, we are still far from understanding how a very small proportion of the satellite cell progeny maintain their stem cell identity when most of their siblings progress through the myogenic program to construct myofibers. © 2018 Elsevier Inc. All rights reserved.

  15. Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

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    Sofia Baptista

    2014-09-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG. Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10 nM decreased DG stem cell self-renewal, while 1 nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase, which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10 nM did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10 nM decreased Sox2+/Sox2+ while increased Sox2−/Sox2− pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10 μM. Moreover, METH (10 nM increased doublecortin (DCX protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers.

  16. An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma.

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    Gujar, Amit D; Le, Son; Mao, Diane D; Dadey, David Y A; Turski, Alice; Sasaki, Yo; Aum, Diane; Luo, Jingqin; Dahiya, Sonika; Yuan, Liya; Rich, Keith M; Milbrandt, Jeffrey; Hallahan, Dennis E; Yano, Hiroko; Tran, David D; Kim, Albert H

    2016-12-20

    Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD + ). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD + synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD + levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD + -dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD + metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.

  17. The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal

    DEFF Research Database (Denmark)

    Stewart, Morag H; Albert, Mareike; Sroczynska, Patrycja

    2015-01-01

    Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias...... compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential.......Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias....... Constitutive genetic deletion of Jarid1b did not impact steady-state hematopoiesis. In contrast, acute deletion of Jarid1b from bone marrow increased peripheral blood T cells and, following secondary transplantation, resulted in loss of bone marrow reconstitution. Our results reveal that deletion of Jarid1b...

  18. Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ER?

    OpenAIRE

    Tsang, Wing Pui; Zhang, Fengjie; He, Qiling; Cai, Waijiao; Huang, Jianhua; Chan, Wai Yee; Shen, Ziyin; Wan, Chao

    2017-01-01

    Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of m...

  19. Muscle satellite cell heterogeneity and self-renewal

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    Motohashi, Norio; Asakura, Atsushi

    2014-01-01

    Adult skeletal muscle possesses extraordinary regeneration capacities. After muscle injury or exercise, large numbers of newly formed muscle fibers are generated within a week as a result of expansion and differentiation of a self-renewing pool of muscle stem cells termed muscle satellite cells. Normally, satellite cells are mitotically quiescent and reside beneath the basal lamina of muscle fibers. Upon regeneration, satellite cells are activated, and give rise to daughter myogenic precursor cells. After several rounds of proliferation, these myogenic precursor cells contribute to the formation of new muscle fibers. During cell division, a minor population of myogenic precursor cells returns to quiescent satellite cells as a self-renewal process. Currently, accumulating evidence has revealed the essential roles of satellite cells in muscle regeneration and the regulatory mechanisms, while it still remains to be elucidated how satellite cell self-renewal is molecularly regulated and how satellite cells are important in aging and diseased muscle. The number of satellite cells is decreased due to the changing niche during ageing, resulting in attenuation of muscle regeneration capacity. Additionally, in Duchenne muscular dystrophy (DMD) patients, the loss of satellite cell regenerative capacity and decreased satellite cell number due to continuous needs for satellite cells lead to progressive muscle weakness with chronic degeneration. Thus, it is necessary to replenish muscle satellite cells continuously. This review outlines recent findings regarding satellite cell heterogeneity, asymmetric division and molecular mechanisms in satellite cell self-renewal which is crucial for maintenance of satellite cells as a muscle stem cell pool throughout life. In addition, we discuss roles in the stem cell niche for satellite cell maintenance, as well as related cell therapies for approaching treatment of DMD. PMID:25364710

  20. Muscle Satellite Cell Heterogeneity and Self-Renewal

    Directory of Open Access Journals (Sweden)

    Norio eMotohashi

    2014-01-01

    Full Text Available Adult skeletal muscle possesses extraordinary regeneration capacities. After muscle injury or exercise, large numbers of newly formed muscle fibers are generated within a week as a result of expansion and differentiation of a self-renewing pool of muscle stem cells termed muscle satellite cells. Normally, satellite cells are mitotically quiescent and reside beneath the basal lamina of muscle fibers. Upon regeneration, satellite cells are activated, and give rise to daughter myogenic precursor cells. After several rounds of proliferation, these myogenic precursor cells contribute to the formation of new muscle fibers. During cell division, a minor population of myogenic precursor cells returns to quiescent satellite cells as a self-renewal process. Currently, accumulating evidence has revealed the essential roles of satellite cells in muscle regeneration and the regulatory mechanisms, while it still remains to be elucidated how satellite cell self-renewal is molecularly regulated and how satellite cells are important in aging and diseased muscle. The number of satellite cells is decreased due to the changing niche during ageing, resulting in attenuation of muscle regeneration capacity. Additionally, in Duchenne muscular dystrophy (DMD patients, the loss of satellite cell regenerative capacity and decreased satellite cell number due to continuous needs for satellite cells lead to progressive muscle weakness with chronic degeneration. Thus, it is necessary to replenish muscle satellite cells continuously. This review outlines recent findings regarding satellite cell heterogeneity, asymmetric division and molecular mechanisms in satellite cell self-renewal which is crucial for maintenance of satellite cells as a muscle stem cell pool throughout life. In addition, we discuss roles in the stem cell niche for satellite cell maintenance, as well as related cell therapies for approaching treatment of DMD.

  1. CSTI High Capacity Power

    International Nuclear Information System (INIS)

    Winter, J.M.

    1989-01-01

    The SP-100 program was established in 1983 by DOD, DOE, and NASA as a joint program to develop the technology necessary for space nuclear power systems for military and civil application. During FY-86 and 87, the NASA SP-100 Advanced Technology Program was devised to maintain the momentum of promising technology advancement efforts started during Phase 1 of SP-100 and to strengthen, in key areas, the chances for successful development and growth capability of space nuclear reactor power systems for future space applications. In FY-88, the Advanced Technology Program was incorporated into NASA's new Civil Space Technology Initiative (CSTI). The CSTI Program was established to provide the foundation for technology development in automation and robotics, information, propulsion, and power. The CSTI High Capacity Power Program builds on the technology efforts of the SP-100 program, incorporates the previous NASA SP-100 Advanced Technology project, and provides a bridge to NASA Project Pathfinder. The elements of CSTI High Capacity Power development include Conversion Systems, Thermal Management, Power Management, System Diagnostics, and Environmental Interactions. Technology advancement in all areas, including materials, is required to assure the high reliability and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall program will develop and demonstrate the technology base required to provide a wide range of modular power systems as well as allowing mission independence from solar and orbital attitude requirements. Several recent advancements in CSTI High Capacity power development will be discussed

  2. Myostatin signals through Pax7 to regulate satellite cell self-renewal

    International Nuclear Information System (INIS)

    McFarlane, Craig; Hennebry, Alex; Thomas, Mark; Plummer, Erin; Ling, Nicholas; Sharma, Mridula; Kambadur, Ravi

    2008-01-01

    Myostatin, a Transforming Growth Factor-beta (TGF-β) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells

  3. CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

    Science.gov (United States)

    Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

    2016-08-01

    Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. p38 MAPK pathway is essential for self-renewal of mouse male germline stem cells (mGSCs).

    Science.gov (United States)

    Niu, Zhiwei; Mu, Hailong; Zhu, Haijing; Wu, Jiang; Hua, Jinlian

    2017-02-01

    Male germline stem cells (mGSCs), also called spermatogonial stem cells (SSCs), constantly generate spermatozoa in male animals. A number of preliminary studies on mechanisms of mGSC self-renewal have previously been conducted, revealing that several factors are involved in this regulated process. The p38 MAPK pathway is widely conserved in multiple cell types in vivo, and plays an important role in cell proliferation, differentiation, inflammation and apoptosis. However, its role in self-renewal of mGSCs has not hitherto been determined. Here, the mouse mGSCs were cultured and their identity was verified by semi-RT-PCR, alkaline phosphatase (AP) staining and immunofluorescence staining. Then, the p38 MAPK pathway was blocked by p38 MAPK-specific inhibitor SB202190. mGSC self-renewal ability was then analysed by observation of morphology, cell number, cell growth analysis, TUNEL incorporation assay and cell cycle analysis. Results showed that mouse mGSC self-renewal ability was significantly inhibited by SB202190. This study showed for the first time that the p38 MAPK pathway plays a key role in maintaining self-renewal capacity of mouse mGSCs, which offers a new self-renewal pathway for these cells and contributes to overall knowledge of the mechanisms of mGSC self-renewal. © 2016 John Wiley & Sons Ltd.

  5. Nrf2 is required to maintain the self-renewal of glioma stem cells

    International Nuclear Information System (INIS)

    Zhu, Jianhong; Wang, Handong; Sun, Qing; Ji, Xiangjun; Zhu, Lin; Cong, Zixiang; Zhou, Yuan; Liu, Huandong; Zhou, Mengliang

    2013-01-01

    Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioma stem cells (GSCs). Self-renewal is a complex biological process necessary for maintaining the glioma stem cells. Nuclear factor rythroid 2-related factor 2(Nrf2) plays a significant role in protecting cells from endogenous and exogenous stresses. Nrf2 is a key nuclear transcription factor that regulates antioxidant response element (ARE)-containing genes. Previous studies have demonstrated the significant role of Nrf2 in the proliferation of glioblastoma, and in their resistance to radioactive therapies. We examined the effect of knocking down Nrf2 in GSCs. Nrf2 expression was down-regulated by shRNA transinfected with lentivirus. Expression levels of Nestin, Nrf2, BMI-1, Sox2 and Cyclin E were assessed by western blotting, quantitative polymerase chain reaction (qPCR) and immunohistochemistry analysis. The capacity for self-renewal in vitro was assessed by genesis of colonies. The capacity for self-renewal in vivo was analyzed by tumor genesis of xenografts in nude mice. Knockdown of Nrf2 inhibited the proliferation of GSCs, and significantly reduced the expression of BMI-1, Sox2 and CyclinE. Knocking down of Nrf2 changed the cell cycle distribution of GSCs by causing an uncharacteristic increase in the proportion of cells in the G2 phase and a decrease in the proportion of cells in the S phase of the cell cycle. Nrf2 is required to maintain the self-renewal of GSCs, and its down-regulation can attenuate the self-renewal of GSCs significantly

  6. 1990s: High Capacity Backbones

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. 1990s: High Capacity Backbones. Backbone capacities increased from 2.5 Gb/s to 100s of Gb/s during the 1990's. Wavelength division multiplexing with 160 waves of 10 Gb/s was commercially available. Several high-capacity backbones built in the US and Europe.

  7. Self-renewal molecular mechanisms of colorectal cancer stem cells

    OpenAIRE

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2016-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...

  8. Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation via Distinct Mechanisms.

    Science.gov (United States)

    Ma, Xing; Zhu, Xiujuan; Han, Yingying; Story, Benjamin; Do, Trieu; Song, Xiaoqing; Wang, Su; Zhang, Ying; Blanchette, Marco; Gogol, Madelaine; Hall, Kate; Peak, Allison; Anoja, Perera; Xie, Ting

    2017-04-24

    Piwi family protein Aubergine (Aub) maintains genome integrity in late germ cells of the Drosophila ovary through Piwi-associated RNA-mediated repression of transposon activities. Although it is highly expressed in germline stem cells (GSCs) and early progeny, it remains unclear whether it plays any roles in early GSC lineage development. Here we report that Aub promotes GSC self-renewal and GSC progeny differentiation. RNA-iCLIP results show that Aub binds the mRNAs encoding self-renewal and differentiation factors in cultured GSCs. Aub controls GSC self-renewal by preventing DNA-damage-induced Chk2 activation and by translationally controlling the expression of self-renewal factors. It promotes GSC progeny differentiation by translationally controlling the expression of differentiation factors, including Bam. Therefore, this study reveals a function of Aub in GSCs and their progeny, which promotes translation of self-renewal and differentiation factors by directly binding to its target mRNAs and interacting with translational initiation factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation

    DEFF Research Database (Denmark)

    Klauke, Karin; Radulović, Višnja; Broekhuis, Mathilde

    2013-01-01

    The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its...... overexpression enhances self-renewal and induces leukaemia. This effect is dependent on integration into polycomb repressive complex-1 (PRC1) and requires H3K27me3 binding. In contrast, overexpression of Cbx2, Cbx4 or Cbx8 results in differentiation and exhaustion of HSCs. ChIP-sequencing analysis shows that Cbx......7 and Cbx8 share most of their targets; we identified approximately 200 differential targets. Whereas genes targeted by Cbx8 are highly expressed in HSCs and become repressed in progenitors, Cbx7 targets show the opposite expression pattern. Thus, Cbx7 preserves HSC self-renewal by repressing...

  10. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma.

    Science.gov (United States)

    Shan, Juanjuan; Shen, Junjie; Liu, Limei; Xia, Feng; Xu, Chuan; Duan, Guangjie; Xu, Yanmin; Ma, Qinghua; Yang, Zhi; Zhang, Qianzhen; Ma, Leina; Liu, Jia; Xu, Senlin; Yan, Xiaochu; Bie, Ping; Cui, Youhong; Bian, Xiu-wu; Qian, Cheng

    2012-09-01

    Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem-cell-related genes are preferentially overexpressed in a fraction of cancer cells of poorly differentiated tumors. However, it is not known whether or how these cancer cells contribute to tumor initiation and progression. Here, our data showed that increased expression of pluripotency transcription factor Nanog in cancer cells correlates with a worse clinical outcome in HCC. Using the Nanog promoter as a reporter system, we could successfully isolate a small subpopulation of Nanog-positive cells. We demonstrate that Nanog-positive cells exhibited enhanced ability of self-renewal, clonogenicity, and initiation of tumors, which are consistent with crucial hallmarks in the definition of cancer stem cells (CSCs). Nanog(Pos) CSCs could differentiate into mature cancer cells in in vitro and in vivo conditions. In addition, we found that Nanog(Pos) CSCs exhibited resistance to therapeutic agents (e.g., sorafenib and cisplatin) and have a high capacity for tumor invasion and metastasis. Knock-down expression of Nanog in Nanog(Pos) CSCs could decrease self-renewal accompanied with decreased expression of stem-cell-related genes and increased expression of mature hepatocyte-related genes. Overexpression of Nanog in Nanog(Neg) cells could restore self-renewal. Furthermore, we found that insulin-like growth factor (IGF)2 and IGF receptor (IGF1R) were up-regulated in Nanog(Pos) CSCs. Knock-down expression of Nanog in Nanog(Pos) CSCs inhibited the expression of IGF1R, and overexpression of Nanog in Nanog(Neg) cells increased the expression of IGF1R. A specific inhibitor of IGF1R signaling could significantly inhibit self-renewal and Nanog expression, indicating that IGF1R signaling participated in Nanog-mediated self-renewal. These data indicate that Nanog could be a novel biomarker for CSCs in HCC, and that Nanog could play a crucial role in maintaining the self-renewal of CSCs through the IGF1R

  11. Self-renewal molecular mechanisms of colorectal cancer stem cells.

    Science.gov (United States)

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2017-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer.

  12. Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

    Science.gov (United States)

    Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

    2018-01-01

    Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

  13. The B-MYB transcriptional network guides cell cycle progression and fate decisions to sustain self-renewal and the identity of pluripotent stem cells.

    Science.gov (United States)

    Zhan, Ming; Riordon, Daniel R; Yan, Bin; Tarasova, Yelena S; Bruweleit, Sarah; Tarasov, Kirill V; Li, Ronald A; Wersto, Robert P; Boheler, Kenneth R

    2012-01-01

    Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity.

  14. TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival.

    Science.gov (United States)

    Chavali, P L; Saini, R K R; Zhai, Q; Vizlin-Hodzic, D; Venkatabalasubramanian, S; Hayashi, A; Johansson, E; Zeng, Z-j; Mohlin, S; Påhlman, S; Hansford, L; Kaplan, D R; Funa, K

    2014-10-30

    Nuclear orphan receptor TLX (Drosophila tailless homolog) is essential for the maintenance of neural stem/progenitor cell self-renewal, but its role in neuroblastoma (NB) is not well understood. Here, we show that TLX is essential for the formation of tumor spheres in three different NB cell lines, when grown in neural stem cell media. We demonstrate that the knock down of TLX in IMR-32 cells diminishes its tumor sphere-forming capacity. In tumor spheres, TLX is coexpressed with the neural progenitor markers Nestin, CD133 and Oct-4. In addition, TLX is coexpressed with the migratory neural progenitor markers CD15 and matrix metalloproteinase-2 (MMP-2) in xenografts of primary NB cells from patients. Subsequently, we show the effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells. We attribute this to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. In support of our findings, we found that TLX expression was high in NB patient tissues when compared with normal peripheral nervous system tissues. Further, the Kaplan-Meier estimator indicated a negative correlation between TLX expression and survival in 88 NB patients. Therefore, our results point at TLX being a crucial player in progression of NB, by promoting self-renewal of NB tumor-initiating cells and altering their migratory and invasive properties.

  15. DNMT1 Maintains Progenitor Function in Self-Renewing Somatic Tissue

    OpenAIRE

    Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.

    2010-01-01

    Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation1,2. DNA methylation3,4,5 provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)6,7 maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintena...

  16. Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ERα.

    Science.gov (United States)

    Tsang, Wing Pui; Zhang, Fengjie; He, Qiling; Cai, Waijiao; Huang, Jianhua; Chan, Wai Yee; Shen, Ziyin; Wan, Chao

    2017-01-16

    Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of mESCs self-renewal is characterized by increased population in S-phase of cell cycle, elevation of Cylin E and Cyclin-dependent kinase 2 (CDK2) and downregulation of p21, p27 and p57. PCR array screening reveals that caudal-related homeobox 2 (Cdx2) and Rbl2/p130 are remarkably suppressed in mESCs treated with Icaritin. siRNA knockdown of Cdx2 or Rbl2/p130 upregulates the expression of Cyclin E, OCT4 and SOX2, and subsequently increases cell proliferation and colony forming efficiency of mESCs. We then demonstrate that Icaritin co-localizes with estrogen receptor alpha (ERα) and activates its nuclear translocation in mESCs. The promotive effect of Icaritin on cell cycle and pluripotency regulators are eliminated by siRNA knockdown of ERα in mESCs. The results suggest that Icaritin enhances mESCs self-renewal by regulating cell cycle machinery and core pluripotency transcription factors mediated by ERα.

  17. Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Hock Chuan Yeo

    Full Text Available Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs. We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs.

  18. SCL, LMO1 and Notch1 Reprogram Thymocytes into Self-Renewing Cells

    Science.gov (United States)

    Rojas-Sutterlin, Shanti; Herblot, Sabine; Hébert, Josée; Sauvageau, Guy; Lemieux, Sébastien; Lécuyer, Eric; Veiga, Diogo F. T.; Hoang, Trang

    2014-01-01

    The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem cells are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model to define the critical initiating events in this disease. First, thymocytes that are reprogrammed by the SCL and LMO1 oncogenic transcription factors into self-renewing pre-leukemic stem cells (pre-LSCs) remain non-malignant, as evidenced by their capacities to generate functional T cells. Second, we provide strong genetic evidence that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1. Moreover, LYL1 can substitute for SCL to reprogram thymocytes in concert with LMO1. In contrast, inhibition of E2A was not sufficient to substitute for SCL, indicating that thymocyte reprogramming requires transcription activation by SCL-LMO1. Third, only a specific subset of normal thymic cells, known as DN3 thymocytes, is susceptible to reprogramming. This is because physiological NOTCH1 signals are highest in DN3 cells compared to other thymocyte subsets. Consistent with this, overexpression of a ligand-independent hyperactive NOTCH1 allele in all immature thymocytes is sufficient to sensitize them to SCL-LMO1, thereby increasing the pool of self-renewing cells. Surprisingly, hyperactive NOTCH1 cannot reprogram thymocytes on its own, despite the fact that NOTCH1 is activated by gain of function mutations in more than 55% of T-ALL cases. Rather, elevating NOTCH1 triggers a parallel pathway involving Hes1 and Myc that dramatically enhances the activity of SCL-LMO1 We conclude that the acquisition of self-renewal and the genesis of pre-LSCs from thymocytes with a finite lifespan represent a critical first event in T-ALL. Finally, LYL1 and LMO1 or LMO2 are co-expressed in most human T-ALL samples, except the cortical T subtype. We therefore anticipate that the self-renewal network

  19. DNMT1 maintains progenitor function in self-renewing somatic tissue.

    Science.gov (United States)

    Sen, George L; Reuter, Jason A; Webster, Daniel E; Zhu, Lilly; Khavari, Paul A

    2010-01-28

    Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A and B, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.

  20. Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

    2012-09-01

    The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

  1. Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C. elegans Germ Line.

    Directory of Open Access Journals (Sweden)

    Amanda Cinquin

    2016-04-01

    Full Text Available Self-renewing organs often experience a decline in function in the course of aging. It is unclear whether chronological age or external factors control this decline, or whether it is driven by stem cell self-renewal-for example, because cycling cells exhaust their replicative capacity and become senescent. Here we assay the relationship between stem cell cycling and senescence in the Caenorhabditis elegans reproductive system, defining this senescence as the progressive decline in "reproductive capacity," i.e. in the number of progeny that can be produced until cessation of reproduction. We show that stem cell cycling diminishes remaining reproductive capacity, at least in part through the DNA damage response. Paradoxically, gonads kept under conditions that preclude reproduction keep cycling and producing cells that undergo apoptosis or are laid as unfertilized gametes, thus squandering reproductive capacity. We show that continued activity is in fact beneficial inasmuch as gonads that are active when reproduction is initiated have more sustained early progeny production. Intriguingly, continued cycling is intermittent-gonads switch between active and dormant states-and in all likelihood stochastic. Other organs face tradeoffs whereby stem cell cycling has the beneficial effect of providing freshly-differentiated cells and the detrimental effect of increasing the likelihood of cancer or senescence; stochastic stem cell cycling may allow for a subset of cells to preserve proliferative potential in old age, which may implement a strategy to deal with uncertainty as to the total amount of proliferation to be undergone over an organism's lifespan.

  2. SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.

    Science.gov (United States)

    Rybak, Adrian P; Tang, Damu

    2013-12-01

    SOX2 is an essential transcription factor for stem cells and plays a role in tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains unclear. We report here a significant upregulation of SOX2 at both mRNA and protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth factor receptor (EGFR) signaling. Activation of EGFR signaling, following the addition of epidermal growth factor (EGF) or ectopic expression of a constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478) blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown reduced the capacity of DU145 PCSCs to grow under anchorage-independent conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively with elevated levels of SOX2 expression compared to xenograft tumors derived from non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in EGFR-mediated self-renewal of DU145 PCSCs. © 2013.

  3. Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes.

    Science.gov (United States)

    Zhao, Jingyao; Chen, Xufeng; Song, Guangrong; Zhang, Jiali; Liu, Haifeng; Liu, Xiaolong

    2017-01-10

    Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate. However, how individual HSC makes the decision between self-renewal and differentiation remains largely unknown. Here we report that ablation of the key epigenetic regulator Uhrf1 in the hematopoietic system depletes the HSC pool, leading to hematopoietic failure and lethality. Uhrf1-deficient HSCs display normal survival and proliferation, yet undergo erythroid-biased differentiation at the expense of self-renewal capacity. Notably, Uhrf1 is required for the establishment of DNA methylation patterns of erythroid-specific genes during HSC division. The expression of these genes is enhanced in the absence of Uhrf1, which disrupts the HSC-division modes by promoting the symmetric differentiation and suppressing the symmetric self-renewal. Moreover, overexpression of one of the up-regulated genes, Gata1, in HSCs is sufficient to phenocopy Uhrf1-deficient HSCs, which show impaired HSC symmetric self-renewal and increased differentiation commitment. Taken together, our findings suggest that Uhrf1 controls the self-renewal versus differentiation of HSC through epigenetically regulating the cell-division modes, thus providing unique insights into the relationship among Uhrf1-mediated DNA methylation, cell-division mode, and HSC fate decision.

  4. Puerarin Suppresses the Self-Renewal of Murine Embryonic Stem Cells by Inhibition of REST-MiR-21 Regulatory Pathway.

    Science.gov (United States)

    Yin, Mengmeng; Yuan, Yin; Cui, Yurong; Hong, Xian; Luo, Hongyan; Hu, Xinwu; Tang, Ming; Hescheler, Jurgen; Xi, Jiaoya

    2015-01-01

    Puerarin shows a wide range of biological activities, including affecting the cardiac differentiation from murine embryonic stem (mES) cells. However, little is known about its effect and mechanism of action on the self-renewal of mES cells. This study aimed to determine the effect of puerarin on the self-renewal and pluripotency of mES cells and its underlying mechanisms. RT-PCR and real-time PCR were used to detect the transcripts of core transcription factors, specific markers for multiple lineages, REST and microRNA-21 (miR-21). Colony-forming assay was performed to estimate the self-renewal capacity of mES cells. Western blotting and wortmannin were employed to explore the role of PI3K/Akt signaling pathway in the inhibitory action of puerarin on REST transcript. Transfected mES cells with antagomir21 were used to confirm the role of miR-21 in the action of puerarin on cell self-renewal. Puerarin significantly decreased the percentage of the self-renewal colonies, and suppressed the transcripts of Oct4, Nanog, Sox2, c-Myc and REST. Besides, PECAM, NCAM and miR-21 were up-regulated both under the self-renewal conditions and at day 4 of differentiation. The PI3K inhibitor wortmannin successfully reversed the mRNA expression changes of REST, Nanog and Sox2. Transfection of antagomir21 efficiently reversed the effects of puerarin on mES cells self-renewal. Inhibition of REST-miR-21 regulatory pathway may be the key mechanism of puerarin-induced suppression of mES cells self-renewal.

  5. Novel insights into embryonic stem cell self-renewal revealed through comparative human and mouse systems biology networks.

    Science.gov (United States)

    Dowell, Karen G; Simons, Allen K; Bai, Hao; Kell, Braden; Wang, Zack Z; Yun, Kyuson; Hibbs, Matthew A

    2014-05-01

    Embryonic stem cells (ESCs), characterized by their ability to both self-renew and differentiate into multiple cell lineages, are a powerful model for biomedical research and developmental biology. Human and mouse ESCs share many features, yet have distinctive aspects, including fundamental differences in the signaling pathways and cell cycle controls that support self-renewal. Here, we explore the molecular basis of human ESC self-renewal using Bayesian network machine learning to integrate cell-type-specific, high-throughput data for gene function discovery. We integrated high-throughput ESC data from 83 human studies (~1.8 million data points collected under 1,100 conditions) and 62 mouse studies (~2.4 million data points collected under 1,085 conditions) into separate human and mouse predictive networks focused on ESC self-renewal to analyze shared and distinct functional relationships among protein-coding gene orthologs. Computational evaluations show that these networks are highly accurate, literature validation confirms their biological relevance, and reverse transcriptase polymerase chain reaction (RT-PCR) validation supports our predictions. Our results reflect the importance of key regulatory genes known to be strongly associated with self-renewal and pluripotency in both species (e.g., POU5F1, SOX2, and NANOG), identify metabolic differences between species (e.g., threonine metabolism), clarify differences between human and mouse ESC developmental signaling pathways (e.g., leukemia inhibitory factor (LIF)-activated JAK/STAT in mouse; NODAL/ACTIVIN-A-activated fibroblast growth factor in human), and reveal many novel genes and pathways predicted to be functionally associated with self-renewal in each species. These interactive networks are available online at www.StemSight.org for stem cell researchers to develop new hypotheses, discover potential mechanisms involving sparsely annotated genes, and prioritize genes of interest for experimental validation

  6. Self-Renewal, Personal Development and Change: An Inexorable Link.

    Science.gov (United States)

    Krupp, Judy-Arin

    1995-01-01

    Self-renewal, personal development, and change create an inexorable link. Change management processes include the following: (1) internal locus of control; (2) freedom from institutional crutches; (3) flexible teaching; (4) recognition of emotional reactions to change; and (5) identification of the causes of indecisiveness and insecurities. (JOW)

  7. Resveratrol Enhances Self-Renewal of Mouse Embryonic Stem Cells.

    Science.gov (United States)

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

    2017-07-01

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

  8. Hematopoietic stem cells : Self-renewing or aging?

    NARCIS (Netherlands)

    de Haan, G

    2002-01-01

    Stem cells are defined by their extensive self-renewal properties, and yet there is abundant evidence of erosion of stem cell functioning during aging. Whereas intracellular repair and protection mechanisms determine the lifespan of an individual cell, here an argument is made that somatic stem

  9. Sonic hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal.

    Directory of Open Access Journals (Sweden)

    Mariana Rodova

    Full Text Available Dysregulation of the sonic hedgehog (Shh signaling pathway has been associated with cancer stem cells (CSC and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4 as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway

  10. Future High Capacity Backbone Networks

    DEFF Research Database (Denmark)

    Wang, Jiayuan

    are proposed. The work focuses on energy efficient routing algorithms in a dynamic optical core network environment, with Generalized MultiProtocol Label Switching (GMPLS) as the control plane. Energy ef- ficient routing algorithms for energy savings and CO2 savings are proposed, and their performance...... aiming for reducing the dynamic part of the energy consumption of the network may increase the fixed part of the energy consumption meanwhile. In the second half of the thesis, the conflict between energy efficiency and Quality of Service (QoS) is addressed by introducing a novel software defined......This thesis - Future High Capacity Backbone Networks - deals with the energy efficiency problems associated with the development of future optical networks. In the first half of the thesis, novel approaches for using multiple/single alternative energy sources for improving energy efficiency...

  11. High current capacity electrical connector

    International Nuclear Information System (INIS)

    Bettis, E.S.; Watts, H.L.

    1976-01-01

    An electrical connector is provided for coupling high current capacity electrical conductors such as copper busses or the like. The connector is arranged in a ''sandwiched'' configuration in which a conductor plate contacts the busses along major surfaces clamped between two stainless steel backing plates. The conductor plate is provided with contact buttons in a spaced array such that the caps of the buttons extend above the conductor plate surface to contact the busses. When clamping bolts provided through openings in the sandwiched arrangement are tightened, Belleville springs provided under the rim of each button cap are compressed and resiliently force the caps into contact with the busses' contacting surfaces to maintain a predetermined electrical contact area provided by the button cap tops. The contact area does not change with changing thermal or mechanical stresses applied to the coupled conductors

  12. Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal

    Science.gov (United States)

    Lackford, Brad; Yao, Chengguo; Charles, Georgette M; Weng, Lingjie; Zheng, Xiaofeng; Choi, Eun-A; Xie, Xiaohui; Wan, Ji; Xing, Yi; Freudenberg, Johannes M; Yang, Pengyi; Jothi, Raja; Hu, Guang; Shi, Yongsheng

    2014-01-01

    mRNA alternative polyadenylation (APA) plays a critical role in post-transcriptional gene control and is highly regulated during development and disease. However, the regulatory mechanisms and functional consequences of APA remain poorly understood. Here, we show that an mRNA 3′ processing factor, Fip1, is essential for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Fip1 promotes stem cell maintenance, in part, by activating the ESC-specific APA profiles to ensure the optimal expression of a specific set of genes, including critical self-renewal factors. Fip1 expression and the Fip1-dependent APA program change during ESC differentiation and are restored to an ESC-like state during somatic reprogramming. Mechanistically, we provide evidence that the specificity of Fip1-mediated APA regulation depends on multiple factors, including Fip1-RNA interactions and the distance between APA sites. Together, our data highlight the role for post-transcriptional control in stem cell self-renewal, provide mechanistic insight on APA regulation in development, and establish an important function for APA in cell fate specification. PMID:24596251

  13. Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruoxing [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States); Guo, Yan-Lin, E-mail: yanlin.guo@usm.edu [Department of Biological Sciences, The University of Southern Mississippi, 118 College Drive 5018, Hattiesburg, MS 39406 (United States)

    2012-10-01

    Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: Black-Right-Pointing-Pointer Inhibition of Cdks slows down mESCs proliferation. Black-Right-Pointing-Pointer mESCs display remarkable recovery capacity from short-term cell cycle interruption. Black-Right-Pointing-Pointer Short-term cell cycle interruption does not compromise mESC self-renewal. Black

  14. Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Wang, Ruoxing; Guo, Yan-Lin

    2012-01-01

    Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. -- Highlights: ► Inhibition of Cdks slows down mESCs proliferation. ► mESCs display remarkable recovery capacity from short-term cell cycle interruption. ► Short-term cell cycle interruption does not compromise mESC self-renewal. ► Oct4 and Nanog are up-regulated via de novo synthesis by cell cycle interruption.

  15. Maintenance of Self-Renewal and Pluripotency in J1 Mouse Embryonic Stem Cells through Regulating Transcription Factor and MicroRNA Expression Induced by PD0325901

    Directory of Open Access Journals (Sweden)

    Zhiying Ai

    2016-01-01

    Full Text Available Embryonic stem cells (ESCs have the ability to grow indefinitely and retain their pluripotency in culture, and this self-renewal capacity is governed by several crucial molecular pathways controlled by specific regulatory genes and epigenetic modifications. It is reported that multiple epigenetic regulators, such as miRNA and pluripotency factors, can be tightly integrated into molecular pathways and cooperate to maintain self-renewal of ESCs. However, mouse ESCs in serum-containing medium seem to be heterogeneous due to the self-activating differentiation signal of MEK/ERK. Thus, to seek for the crucial miRNA and key regulatory genes that establish ESC properties in MEK/ERK pathway, we performed microarray analysis and small RNA deep-sequencing of J1 mESCs treated with or without PD0325901 (PD, a well-known inhibitor of MEK/ERK signal pathway, followed by verification of western blot analysis and quantitative real-time PCR verification; we found that PD regulated the transcript expressions related to self-renewal and differentiation and antagonized the action of retinoic acid- (RA- induced differentiation. Moreover, PD can significantly modulate the expressions of multiple miRNAs that have crucial functions in ESC development. Overall, our results demonstrate that PD could enhance ESC self-renewal capacity both by key regulatory genes and ES cell-specific miRNA, which in turn influences ESC self-renewal and cellular differentiation.

  16. Targeting proapoptotic protein BAD inhibits survival and self-renewal of cancer stem cells.

    Science.gov (United States)

    Sastry, K S R; Al-Muftah, M A; Li, Pu; Al-Kowari, M K; Wang, E; Ismail Chouchane, A; Kizhakayil, D; Kulik, G; Marincola, F M; Haoudi, A; Chouchane, L

    2014-12-01

    Emerging evidence suggests that the resistance of cancer stem cells (CSC) to many conventional therapies is one of the major limiting factors of cancer therapy efficacy. Identification of mechanisms responsible for survival and self-renewal of CSC will help design new therapeutic strategies that target and eliminate both differentiated cancer cells and CSC. Here we demonstrated the potential role of proapoptotic protein BAD in the biology of CSC in melanoma, prostate and breast cancers. We enriched CD44(+)/CD24(-) cells (CSC) by tumorosphere formation and purified this population by FACS. Both spheres and CSC exhibited increased potential for proliferation, migration, invasion, sphere formation, anchorage-independent growth, as well as upregulation of several stem cell-associated markers. We showed that the phosphorylation of BAD is essential for the survival of CSC. Conversely, ectopic expression of a phosphorylation-deficient mutant BAD induced apoptosis in CSC. This effect was enhanced by treatment with a BH3-mimetic, ABT-737. Both pharmacological agents that inhibit survival kinases and growth factors that are involved in drug resistance delivered their respective cytotoxic and protective effects by modulating the BAD phosphorylation in CSC. Furthermore, the frequency and self-renewal capacity of CSC was significantly reduced by knocking down the BAD expression. Consistent with our in vitro results, significant phosphorylation of BAD was found in CD44(+) CSC of 83% breast tumor specimens. In addition, we also identified a positive correlation between BAD expression and disease stage in prostate cancer, suggesting a role of BAD in tumor advancement. Our studies unveil the role of BAD in the survival and self-renewal of CSC and propose BAD not only as an attractive target for cancer therapy but also as a marker of tumor progression.

  17. Transient inhibition of cell proliferation does not compromise self-renewal of mouse embryonic stem cells.

    Science.gov (United States)

    Wang, Ruoxing; Guo, Yan-Lin

    2012-10-01

    Embryonic stem cells (ESCs) have unlimited capacity for self-renewal and can differentiate into various cell types when induced. They also have an unusual cell cycle control mechanism driven by constitutively active cyclin dependent kinases (Cdks). In mouse ESCs (mESCs). It is proposed that the rapid cell proliferation could be a necessary part of mechanisms that maintain mESC self-renewal and pluripotency, but this hypothesis is not in line with the finding in human ESCs (hESCs) that the length of the cell cycle is similar to differentiated cells. Therefore, whether rapid cell proliferation is essential for the maintenance of mESC state remains unclear. We provide insight into this uncertainty through chemical intervention of mESC cell cycle. We report here that inhibition of Cdks with olomoucine II can dramatically slow down cell proliferation of mESCs with concurrent down-regulation of cyclin A, B and E, and the activation of the Rb pathway. However, mESCs display can recover upon the removal of olomoucine II and are able to resume normal cell proliferation without losing self-renewal and pluripotency, as demonstrated by the expression of ESC markers, colony formation, embryoid body formation, and induced differentiation. We provide a mechanistic explanation for these observations by demonstrating that Oct4 and Nanog, two major transcription factors that play critical roles in the maintenance of ESC properties, are up-regulated via de novo protein synthesis when the cells are exposed to olomoucine II. Together, our data suggest that short-term inhibition of cell proliferation does not compromise the basic properties of mESCs. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Metabolic rate determines haematopoietic stem cell self-renewal.

    Science.gov (United States)

    Sastry, P S R K

    2004-01-01

    The number of haematopoietic stem cells (HSCs) per animal is conserved across species. This means the HSCs need to maintain hematopoiesis over a longer period in larger animals. This would result in the requirement of stem cell self-renewal. At present the three existing models are the stochastic model, instructive model and the third more recently proposed is the chiaro-scuro model. It is a well known allometric law that metabolic rate scales to the three quarter power. Larger animals have a lower metabolic rate, compared to smaller animals. Here it is being hypothesized that metabolic rate determines haematopoietic stem cell self-renewal. At lower metabolic rate the stem cells commit for self-renewal, where as at higher metabolic rate they become committed to different lineages. The present hypothesis can explain the salient features of the different models. Recent findings regarding stem cell self-renewal suggest an important role for Wnt proteins and their receptors known as frizzleds, which are an important component of cell signaling pathway. The role of cGMP in the Wnts action provides further justification for the present hypothesis as cGMP is intricately linked to metabolic rate. One can also explain the telomere homeostasis by the present hypothesis. One prediction of the present hypothesis is with reference to the limit of cell divisions known as Hayflick limit, here it is being suggested that this is the result of metabolic rate in laboratory conditions and there can be higher number of cell divisions in vivo if the metabolic rate is lower. Copyright 2004 Elsevier Ltd.

  19. High capacity carbon dioxide sorbent

    Science.gov (United States)

    Dietz, Steven Dean; Alptekin, Gokhan; Jayaraman, Ambalavanan

    2015-09-01

    The present invention provides a sorbent for the removal of carbon dioxide from gas streams, comprising: a CO.sub.2 capacity of at least 9 weight percent when measured at 22.degree. C. and 1 atmosphere; an H.sub.2O capacity of at most 15 weight percent when measured at 25.degree. C. and 1 atmosphere; and an isosteric heat of adsorption of from 5 to 8.5 kilocalories per mole of CO.sub.2. The invention also provides a carbon sorbent in a powder, a granular or a pellet form for the removal of carbon dioxide from gas streams, comprising: a carbon content of at least 90 weight percent; a nitrogen content of at least 1 weight percent; an oxygen content of at most 3 weight percent; a BET surface area from 50 to 2600 m.sup.2/g; and a DFT micropore volume from 0.04 to 0.8 cc/g.

  20. Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.

    Science.gov (United States)

    Yan, Xiao; Himburg, Heather A; Pohl, Katherine; Quarmyne, Mamle; Tran, Evelyn; Zhang, Yurun; Fang, Tiancheng; Kan, Jenny; Chao, Nelson J; Zhao, Liman; Doan, Phuong L; Chute, John P

    2016-11-01

    Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10 m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10 +/+ mice. After total body irradiation (TBI), Grb10 m/+ mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution, as compared to Grb10 +/+ mice. Grb10-deficient HSCs displayed increased proliferation after competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10-deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene Grb10 in regulating HSC self-renewal and regeneration and suggests that the inhibition of Grb10 can promote hematopoietic regeneration in vivo. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Cell-type-specific predictive network yields novel insights into mouse embryonic stem cell self-renewal and cell fate.

    Directory of Open Access Journals (Sweden)

    Karen G Dowell

    Full Text Available Self-renewal, the ability of a stem cell to divide repeatedly while maintaining an undifferentiated state, is a defining characteristic of all stem cells. Here, we clarify the molecular foundations of mouse embryonic stem cell (mESC self-renewal by applying a proven Bayesian network machine learning approach to integrate high-throughput data for protein function discovery. By focusing on a single stem-cell system, at a specific developmental stage, within the context of well-defined biological processes known to be active in that cell type, we produce a consensus predictive network that reflects biological reality more closely than those made by prior efforts using more generalized, context-independent methods. In addition, we show how machine learning efforts may be misled if the tissue specific role of mammalian proteins is not defined in the training set and circumscribed in the evidential data. For this study, we assembled an extensive compendium of mESC data: ∼2.2 million data points, collected from 60 different studies, under 992 conditions. We then integrated these data into a consensus mESC functional relationship network focused on biological processes associated with embryonic stem cell self-renewal and cell fate determination. Computational evaluations, literature validation, and analyses of predicted functional linkages show that our results are highly accurate and biologically relevant. Our mESC network predicts many novel players involved in self-renewal and serves as the foundation for future pluripotent stem cell studies. This network can be used by stem cell researchers (at http://StemSight.org to explore hypotheses about gene function in the context of self-renewal and to prioritize genes of interest for experimental validation.

  2. SVM classifier to predict genes important for self-renewal and pluripotency of mouse embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Xu Huilei

    2010-12-01

    Full Text Available Abstract Background Mouse embryonic stem cells (mESCs are derived from the inner cell mass of a developing blastocyst and can be cultured indefinitely in-vitro. Their distinct features are their ability to self-renew and to differentiate to all adult cell types. Genes that maintain mESCs self-renewal and pluripotency identity are of interest to stem cell biologists. Although significant steps have been made toward the identification and characterization of such genes, the list is still incomplete and controversial. For example, the overlap among candidate self-renewal and pluripotency genes across different RNAi screens is surprisingly small. Meanwhile, machine learning approaches have been used to analyze multi-dimensional experimental data and integrate results from many studies, yet they have not been applied to specifically tackle the task of predicting and classifying self-renewal and pluripotency gene membership. Results For this study we developed a classifier, a supervised machine learning framework for predicting self-renewal and pluripotency mESCs stemness membership genes (MSMG using support vector machines (SVM. The data used to train the classifier was derived from mESCs-related studies using mRNA microarrays, measuring gene expression in various stages of early differentiation, as well as ChIP-seq studies applied to mESCs profiling genome-wide binding of key transcription factors, such as Nanog, Oct4, and Sox2, to the regulatory regions of other genes. Comparison to other classification methods using the leave-one-out cross-validation method was employed to evaluate the accuracy and generality of the classification. Finally, two sets of candidate genes from genome-wide RNA interference screens are used to test the generality and potential application of the classifier. Conclusions Our results reveal that an SVM approach can be useful for prioritizing genes for functional validation experiments and complement the analyses of high

  3. SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

    2014-09-18

    Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

  4. Protein kinase C regulates human pluripotent stem cell self-renewal.

    Directory of Open Access Journals (Sweden)

    Masaki Kinehara

    Full Text Available The self-renewal of human pluripotent stem (hPS cells including embryonic stem and induced pluripotent stem cells have been reported to be supported by various signal pathways. Among them, fibroblast growth factor-2 (FGF-2 appears indispensable to maintain self-renewal of hPS cells. However, downstream signaling of FGF-2 has not yet been clearly understood in hPS cells.In this study, we screened a kinase inhibitor library using a high-throughput alkaline phosphatase (ALP activity-based assay in a minimal growth factor-defined medium to understand FGF-2-related molecular mechanisms regulating self-renewal of hPS cells. We found that in the presence of FGF-2, an inhibitor of protein kinase C (PKC, GF109203X (GFX, increased ALP activity. GFX inhibited FGF-2-induced phosphorylation of glycogen synthase kinase-3β (GSK-3β, suggesting that FGF-2 induced PKC and then PKC inhibited the activity of GSK-3β. Addition of activin A increased phosphorylation of GSK-3β and extracellular signal-regulated kinase-1/2 (ERK-1/2 synergistically with FGF-2 whereas activin A alone did not. GFX negated differentiation of hPS cells induced by the PKC activator, phorbol 12-myristate 13-acetate whereas Gö6976, a selective inhibitor of PKCα, β, and γ isoforms could not counteract the effect of PMA. Intriguingly, functional gene analysis by RNA interference revealed that the phosphorylation of GSK-3β was reduced by siRNA of PKCδ, PKCε, and ζ, the phosphorylation of ERK-1/2 was reduced by siRNA of PKCε and ζ, and the phosphorylation of AKT was reduced by PKCε in hPS cells.Our study suggested complicated cross-talk in hPS cells that FGF-2 induced the phosphorylation of phosphatidylinositol-3 kinase (PI3K/AKT, mitogen-activated protein kinase/ERK-1/2 kinase (MEK, PKC/ERK-1/2 kinase, and PKC/GSK-3β. Addition of GFX with a MEK inhibitor, U0126, in the presence of FGF-2 and activin A provided a long-term stable undifferentiated state of hPS cells even though h

  5. Protein Kinase C Regulates Human Pluripotent Stem Cell Self-Renewal

    Science.gov (United States)

    Kinehara, Masaki; Kawamura, Suguru; Tateyama, Daiki; Suga, Mika; Matsumura, Hiroko; Mimura, Sumiyo; Hirayama, Noriko; Hirata, Mitsuhi; Uchio-Yamada, Kozue; Kohara, Arihiro; Yanagihara, Kana; Furue, Miho K.

    2013-01-01

    Background The self-renewal of human pluripotent stem (hPS) cells including embryonic stem and induced pluripotent stem cells have been reported to be supported by various signal pathways. Among them, fibroblast growth factor-2 (FGF-2) appears indispensable to maintain self-renewal of hPS cells. However, downstream signaling of FGF-2 has not yet been clearly understood in hPS cells. Methodology/Principal Findings In this study, we screened a kinase inhibitor library using a high-throughput alkaline phosphatase (ALP) activity-based assay in a minimal growth factor-defined medium to understand FGF-2-related molecular mechanisms regulating self-renewal of hPS cells. We found that in the presence of FGF-2, an inhibitor of protein kinase C (PKC), GF109203X (GFX), increased ALP activity. GFX inhibited FGF-2-induced phosphorylation of glycogen synthase kinase-3β (GSK-3β), suggesting that FGF-2 induced PKC and then PKC inhibited the activity of GSK-3β. Addition of activin A increased phosphorylation of GSK-3β and extracellular signal-regulated kinase-1/2 (ERK-1/2) synergistically with FGF-2 whereas activin A alone did not. GFX negated differentiation of hPS cells induced by the PKC activator, phorbol 12-myristate 13-acetate whereas Gö6976, a selective inhibitor of PKCα, β, and γ isoforms could not counteract the effect of PMA. Intriguingly, functional gene analysis by RNA interference revealed that the phosphorylation of GSK-3β was reduced by siRNA of PKCδ, PKCε, and ζ, the phosphorylation of ERK-1/2 was reduced by siRNA of PKCε and ζ, and the phosphorylation of AKT was reduced by PKCε in hPS cells. Conclusions/Significance Our study suggested complicated cross-talk in hPS cells that FGF-2 induced the phosphorylation of phosphatidylinositol-3 kinase (PI3K)/AKT, mitogen-activated protein kinase/ERK-1/2 kinase (MEK), PKC/ERK-1/2 kinase, and PKC/GSK-3β. Addition of GFX with a MEK inhibitor, U0126, in the presence of FGF-2 and activin A provided a long

  6. GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

    Directory of Open Access Journals (Sweden)

    Antonela Bonafina

    2018-03-01

    Full Text Available Summary: The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2, promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. : In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation. Keywords: GDNF, GFRα1, cortical precursors, proliferation, postmitotic neurons, neuronal differentiation

  7. Involvement of extracellular factors in maintaining self-renewal of neural stem cell by nestin.

    Science.gov (United States)

    Di, Chun Guang; Xiang, Andy Peng; Jia, Lei; Liu, Jun Feng; Lahn, Bruce T; Ma, Bao Feng

    2014-07-09

    Nestin knockout leads to embryonic lethality and self-renewal deficiency in neural stem cells (NSCs). However, how nestin maintains self-renewal remains uncertain. Here, we used the dosage effect of nestin in heterozygous mice (Nes+/-) to study self-renewal of NSCs. With existing extracellular signaling in vivo or in vitro, nestin levels do not affect proliferation ability or apoptosis when compared between Nes+/- and Nes+/+ NSCs. However, self-renewal ability of Nes+/- NSCs is impaired when plated at a low cell density and completely lost at a clonal density. This deficiency in self-renewal at a clonal density is rescued using a medium conditioned by Nes+/+ NSCs. In addition, the Akt signaling pathway is altered at low density and reversed by conditioned medium. Our data show that secreted factors contribute toward maintaining self-renewal of NSCs by nestin, potentially through Akt signaling.

  8. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer.

    Science.gov (United States)

    Singh, Sandeep; Trevino, Jose; Bora-Singhal, Namrata; Coppola, Domenico; Haura, Eric; Altiok, Soner; Chellappan, Srikumar P

    2012-09-25

    Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs), Hoechst 33342 dye effluxing side population (SP) cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549), as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of stem-like cells from NSCLC. Therefore, the outcome of the

  9. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Singh Sandeep

    2012-09-01

    Full Text Available Abstract Background Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs, Hoechst 33342 dye effluxing side population (SP cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. Results SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549, as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Conclusions Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of

  10. ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal

    OpenAIRE

    Morimoto, Hiroko; Iwata, Kazumi; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Kanatsu-Shinohara, Mito; Morimoto, Takeshi; Yabe-Nishimura, Chihiro; Shinohara, Takashi

    2013-01-01

    Reactive oxygen species (ROS) generation is implicated in stem cell self-renewal in several tissues but is thought to be detrimental for spermatogenesis as well as spermatogonial stem cells (SSCs). Using cultured SSCs, we show that ROS are generated via the AKT and MEK signaling pathways under conditions where the growth factors glial cell line-derived neurotrophic factor and fibroblast growth factor 2 drive SSC self-renewal and, instead, stimulate self-renewal at physiological levels. SSCs d...

  11. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

    OpenAIRE

    Soucie, E.L.; Weng, Z.; Geirsdottir, L.; Molawi, K.; Maurizio, J.; Fenouil, R.; Mossadegh-Keller, N.; Gimenez, G.; VanHille, L.; Beniazza, M.; Favret, J.; Berruyer, C.; Perrin, P.; Hacohen, N.; Andrau, J.C.

    2016-01-01

    Differentiated macrophages can self-renew in tissues and expand long-term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. Single cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down...

  12. Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation

    OpenAIRE

    Mei, Xing-Xing; Wang, Jian; Wu, Ji

    2015-01-01

    Spermatogonial stem cells (SSCs), the stem cells responsible for male fertility, are one of a small number of cells with the abilities of both self-renewal and generation of large numbers of haploid cells. Technology improvements, most importantly, transplantation assays and in vitro culture systems have greatly expanded our understanding of SSC self-renewal and differentiation. Many important molecules crucial for the balance between self-renewal and differentiation have been recently identi...

  13. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

    Energy Technology Data Exchange (ETDEWEB)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín [Programa de Doctorado en Ciencias Biomédicas, Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, México (Mexico); Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México 07360, México (Mexico); Ocadiz-Delgado, Rodolfo; García-Villa, Enrique [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México 07360, México (Mexico); Bonilla-Delgado, José [Unidad de Investigación, Hospital Juárez de México, Ciudad de México 07760, México (Mexico); Lagunas-Martínez, Alfredo [División de Biología Molecular de Patógenos, CISEI, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México (Mexico); and others

    2016-12-15

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E{sub 2}) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E{sub 2} on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E{sub 2} in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. -- Graphical abstract: The HPV16 E7 oncoprotein and 17β-estradiol are involved in the upregulation of Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal ability of cancer stem cells in cervical cancer. - Highlights: •The HPV16 E7 oncoprotein enhances cellular proliferation and dedifferentiation. •The E7 oncoprotein induces stemness-related genes expression in vivo and in vitro. •The 17β-estradiol induces stemness-related genes expression in vivo. •The HPV16 E7 oncoprotein is involved in the cell self-renewal of cancer cells.

  14. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal

    International Nuclear Information System (INIS)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Ocadiz-Delgado, Rodolfo; García-Villa, Enrique; Bonilla-Delgado, José; Lagunas-Martínez, Alfredo

    2016-01-01

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E 2 ) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E 2 on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E 2 in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. -- Graphical abstract: The HPV16 E7 oncoprotein and 17β-estradiol are involved in the upregulation of Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal ability of cancer stem cells in cervical cancer. - Highlights: •The HPV16 E7 oncoprotein enhances cellular proliferation and dedifferentiation. •The E7 oncoprotein induces stemness-related genes expression in vivo and in vitro. •The 17β-estradiol induces stemness-related genes expression in vivo. •The HPV16 E7 oncoprotein is involved in the cell self-renewal of cancer cells.

  15. Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation

    Directory of Open Access Journals (Sweden)

    Xing-Xing Mei

    2015-06-01

    Full Text Available Spermatogonial stem cells (SSCs, the stem cells responsible for male fertility, are one of a small number of cells with the abilities of both self-renewal and generation of large numbers of haploid cells. Technology improvements, most importantly, transplantation assays and in vitro culture systems have greatly expanded our understanding of SSC self-renewal and differentiation. Many important molecules crucial for the balance between self-renewal and differentiation have been recently identified although the exact mechanism(s remain largely undefined. In this review, we give a brief introduction to SSCs, and then focus on extrinsic and intrinsic factors controlling SSCs self-renewal and differentiation.

  16. Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation.

    Science.gov (United States)

    Mei, Xing-Xing; Wang, Jian; Wu, Ji

    2015-01-01

    Spermatogonial stem cells (SSCs), the stem cells responsible for male fertility, are one of a small number of cells with the abilities of both self-renewal and generation of large numbers of haploid cells. Technology improvements, most importantly, transplantation assays and in vitro culture systems have greatly expanded our understanding of SSC self-renewal and differentiation. Many important molecules crucial for the balance between self-renewal and differentiation have been recently identified although the exact mechanism(s) remain largely undefined. In this review, we give a brief introduction to SSCs, and then focus on extrinsic and intrinsic factors controlling SSCs self-renewal and differentiation.

  17. Adhesion-mediated self-renewal abilities of Ph+ blastoma cells

    International Nuclear Information System (INIS)

    Funayama, Keiji; Saito-Kurimoto, Yumi; Ebihara, Yasuhiro; Shimane, Miyuki; Nomura, Hitoshi; Tsuji, Ko-ichiro; Asano, Shigetaka

    2010-01-01

    The Philadelphia chromosome-positive blastoma, maintained by serial subcutaneous transplantation in nude mice, is a highly proliferating biological mass consisting of homogenous CD34 + CD38 - myeloblastoid cells. These cells newly evolved from pluripotent leukemia stem cells of chronic myeloid leukemia in the chronic phase. Therefore, this mass may provide a unique tool for better understanding cellular and molecular mechanisms of self-renewal of leukemia stem cells. In this paper, we demonstrated that intravenously injected blastoma cells can cause Ph+ blastic leukemia with multiple invasive foci in NOD/SCID mice but not in nude mice. In addition, using an in vitro culture system, we clearly showed that blastoma cell adhesion to OP9 stromal cells accelerates blastoma cell proliferation that is associated with up-regulation of BMI1 gene expression; increased levels of β-catenin and the Notch1 intra-cellular domain; and changed the expression pattern of variant CD44 forms, which are constitutively expressed in these blastoma cells. These findings strongly suggest that adhesion of leukemic stem cells to stromal cells via CD44 might be indispensable for their cellular defense against attack by immune cells and for maintenance of their self-renewal ability.

  18. miR-99 regulates normal and malignant hematopoietic stem cell self-renewal.

    Science.gov (United States)

    Khalaj, Mona; Woolthuis, Carolien M; Hu, Wenhuo; Durham, Benjamin H; Chu, S Haihua; Qamar, Sarah; Armstrong, Scott A; Park, Christopher Y

    2017-07-21

    The microRNA-99 ( miR-99 ) family comprises a group of broadly conserved microRNAs that are highly expressed in hematopoietic stem cells (HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny. Herein, we show that miR-99 regulates self-renewal in both HSCs and LSCs. miR-99 maintains HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants. Confirming miR-99 's role in established AML, miR-99 inhibition induced primary AML patient blasts to undergo differentiation. A forward genetic shRNA library screen revealed Hoxa1 as a critical mediator of miR-99 function in HSC maintenance, and this observation was independently confirmed in both HSCs and LSCs. Together, these studies demonstrate the importance of noncoding RNAs in the regulation of HSC and LSC function and identify miR-99 as a critical regulator of stem cell self-renewal. © 2017 Khalaj et al.

  19. Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

    Science.gov (United States)

    Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

    2018-05-24

    Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

  20. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

    1978-01-01

    The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

  1. Proinflammatory cytokine tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) suppresses satellite cell self-renewal through inversely modulating Notch and NF-κB signaling pathways.

    Science.gov (United States)

    Ogura, Yuji; Mishra, Vivek; Hindi, Sajedah M; Kuang, Shihuan; Kumar, Ashok

    2013-12-06

    Satellite cell self-renewal is an essential process to maintaining the robustness of skeletal muscle regenerative capacity. However, extrinsic factors that regulate self-renewal of satellite cells are not well understood. Here, we demonstrate that TWEAK cytokine reduces the proportion of Pax7(+)/MyoD(-) cells (an index of self-renewal) on myofiber explants and represses multiple components of Notch signaling in satellite cell cultures. The number of Pax7(+) cells is significantly increased in skeletal muscle of TWEAK knock-out (KO) mice compared with wild-type in response to injury. Furthermore, Notch signaling is significantly elevated in cultured satellite cells and in regenerating myofibers of TWEAK-KO mice. Forced activation of Notch signaling through overexpression of the Notch1 intracellular domain (N1ICD) rescued the TWEAK-mediated inhibition of satellite cell self-renewal. TWEAK also activates the NF-κB transcription factor in satellite cells and inhibition of NF-κB significantly improved the number of Pax7(+) cells in TWEAK-treated cultures. Furthermore, our results demonstrate that a reciprocal interaction between NF-κB and Notch signaling governs the inhibitory effect of TWEAK on satellite cell self-renewal. Collectively, our study demonstrates that TWEAK suppresses satellite cell self-renewal through activating NF-κB and repressing Notch signaling.

  2. Self-renewal and cancer of the gut: two sides of a coin.

    NARCIS (Netherlands)

    Radtke, F.; Clevers, J.C.

    2005-01-01

    The intestinal epithelium follows the paradigms of stem cell biology established for other self-renewing tissues. With a unique topology, it constitutes a two-dimensional structure folded into valleys and hills: the proliferative crypts and the differentiated villi. Its unprecedented self-renewal

  3. Fibroblast growth factors as regulators of stem cell self-renewal and aging

    NARCIS (Netherlands)

    Yeoh, Joyce S. G.; de Haan, Gerald

    Organ and tissue dysfunction which is readily observable during aging results from a loss of cellular homeostasis and reduced stem cell self-renewal. Over the past 10 years, studies have been aimed at delineating growth factors that will sustain and promote the self-renewal potential of stem cells

  4. STAT5-mediated self-renewal of normal hematopoietic and leukemic stem cells

    NARCIS (Netherlands)

    Schepers, Hein; Wierenga, Albertus T. J.; Vellenga, Edo; Schuringa, Jan Jacob

    2012-01-01

    The level of transcription factor activity critically regulates cell fate decisions such as hematopoietic stem cell self-renewal and differentiation. The balance between hematopoietic stem cell self-renewal and differentiation needs to be tightly controlled, as a shift toward differentiation might

  5. Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.

    Science.gov (United States)

    Kanatsu-Shinohara, Mito; Tanaka, Takashi; Ogonuki, Narumi; Ogura, Atsuo; Morimoto, Hiroko; Cheng, Pei Feng; Eisenman, Robert N; Trumpp, Andreas; Shinohara, Takashi

    2016-12-01

    Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division. © 2016 Kanatsu-Shinohara et al.; Published by Cold Spring Harbor Laboratory Press.

  6. The Hippo pathway: key interaction and catalytic domains in organ growth control, stem cell self-renewal and tissue regeneration.

    Science.gov (United States)

    Cherrett, Claire; Furutani-Seiki, Makoto; Bagby, Stefan

    2012-01-01

    The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homoeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), consequently disabling their transcriptional co-activation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins.

  7. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.

    Science.gov (United States)

    Soucie, Erinn L; Weng, Ziming; Geirsdóttir, Laufey; Molawi, Kaaweh; Maurizio, Julien; Fenouil, Romain; Mossadegh-Keller, Noushine; Gimenez, Gregory; VanHille, Laurent; Beniazza, Meryam; Favret, Jeremy; Berruyer, Carole; Perrin, Pierre; Hacohen, Nir; Andrau, J-C; Ferrier, Pierre; Dubreuil, Patrice; Sidow, Arend; Sieweke, Michael H

    2016-02-12

    Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells. Copyright © 2016, American Association for the Advancement of Science.

  8. Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

    Science.gov (United States)

    Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

    2014-11-11

    Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

  9. Low Oxygen Modulates Multiple Signaling Pathways, Increasing Self-Renewal, While Decreasing Differentiation, Senescence, and Apoptosis in Stromal MIAMI Cells

    Science.gov (United States)

    Rios, Carmen; D'Ippolito, Gianluca; Curtis, Kevin M.; Delcroix, Gaëtan J.-R.; Gomez, Lourdes A.; El Hokayem, Jimmy; Rieger, Megan; Parrondo, Ricardo; de las Pozas, Alicia; Perez-Stable, Carlos; Howard, Guy A.

    2016-01-01

    Human bone marrow multipotent mesenchymal stromal cell (hMSC) number decreases with aging. Subpopulations of hMSCs can differentiate into cells found in bone, vasculature, cartilage, gut, and other tissues and participate in their repair. Maintaining throughout adult life such cell subpopulations should help prevent or delay the onset of age-related degenerative conditions. Low oxygen tension, the physiological environment in progenitor cell-rich regions of the bone marrow microarchitecture, stimulates the self-renewal of marrow-isolated adult multilineage inducible (MIAMI) cells and expression of Sox2, Nanog, Oct4a nuclear accumulation, Notch intracellular domain, notch target genes, neuronal transcriptional repressor element 1 (RE1)-silencing transcription factor (REST), and hypoxia-inducible factor-1 alpha (HIF-1α), and additionally, by decreasing the expression of (i) the proapoptotic proteins, apoptosis-inducing factor (AIF) and Bak, and (ii) senescence-associated p53 expression and β-galactosidase activity. Furthermore, low oxygen increases canonical Wnt pathway signaling coreceptor Lrp5 expression, and PI3K/Akt pathway activation. Lrp5 inhibition decreases self-renewal marker Sox2 mRNA, Oct4a nuclear accumulation, and cell numbers. Wortmannin-mediated PI3K/Akt pathway inhibition leads to increased osteoblastic differentiation at both low and high oxygen tension. We demonstrate that low oxygen stimulates a complex signaling network involving PI3K/Akt, Notch, and canonical Wnt pathways, which mediate the observed increase in nuclear Oct4a and REST, with simultaneous decrease in p53, AIF, and Bak. Collectively, these pathway activations contribute to increased self-renewal with concomitant decreased differentiation, cell cycle arrest, apoptosis, and/or senescence in MIAMI cells. Importantly, the PI3K/Akt pathway plays a central mechanistic role in the oxygen tension-regulated self-renewal versus osteoblastic differentiation of progenitor cells. PMID:27059084

  10. High capacity photonic integrated switching circuits

    NARCIS (Netherlands)

    Albores Mejia, A.

    2011-01-01

    As the demand for high-capacity data transfer keeps increasing in high performance computing and in a broader range of system area networking environments; reconfiguring the strained networks at ever faster speeds with larger volumes of traffic has become a huge challenge. Formidable bottlenecks

  11. The HPV16 E7 oncoprotein increases the expression of Oct3/4 and stemness-related genes and augments cell self-renewal.

    Science.gov (United States)

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Ocadiz-Delgado, Rodolfo; García-Villa, Enrique; Bonilla-Delgado, José; Lagunas-Martínez, Alfredo; Tapia, Jesús Santa-Olalla; Lambert, Paul F; García-Carrancá, Alejandro; Gariglio, Patricio

    2016-12-01

    Oct3/4 is a transcription factor involved in maintenance of the pluripotency and self-renewal of stem cells. The E7 oncoprotein and 17β-estradiol (E 2 ) are key factors in cervical carcinogenesis. In the present study, we aimed to investigate the effect of the HPV16 E7 oncoprotein and E 2 on the expression pattern of Oct3/4, Sox2, Nanog and Fgf4. We also determined whether the E7 oncoprotein is associated with cell self-renewal. The results showed that Oct3/4, Sox2, Nanog and Fgf4 were upregulated by the E7 oncoprotein in vivo and in vitro and implicate E 2 in the upregulation of these factors in vivo. We also demonstrated that E7 is involved in cell self-renewal, suggesting that the HPV16 E7 oncoprotein upregulates Oct3/4, Sox2, Nanog and Fgf4 expression to maintain the self-renewal capacity of cancer stem cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2.

    Science.gov (United States)

    Ting, Stephen B; Deneault, Eric; Hope, Kristin; Cellot, Sonia; Chagraoui, Jalila; Mayotte, Nadine; Dorn, Jonas F; Laverdure, Jean-Philippe; Harvey, Michael; Hawkins, Edwin D; Russell, Sarah M; Maddox, Paul S; Iscove, Norman N; Sauvageau, Guy

    2012-03-15

    The stem cell-intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions.

  13. Differential Connexin Function Enhances Self-Renewal in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Masahiro Hitomi

    2015-05-01

    Full Text Available The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43, but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.

  14. High capacity getter pump for UHV operation

    International Nuclear Information System (INIS)

    Manini, P.; Marino, M.; Belloni, F.; Porro, M.

    1993-01-01

    UHV pumps based on non-evaporable getter coated strips find widespread use in particle accelerators, synchrotron radiation machines and nuclear fusion experimental devices. Depending on the geometric constraints, pressure operation conditions and the foreseen gas loads, optimized getter structures, such as modules and cartridges, can be designed and assembled into a high-efficiency pump. In the present paper, the design and performance of a newly conceived High Capacity Getter Pump (HCGP) based on sintered getter bodies, in the shape of blades instead of strips, is illustrated. The porosity and the specific surface area of the blades and their arrangement in the cartridge have been optimized to significantly increase sorption capacity at a given speed. These pumps are well suited for those applications where a very high gas load is expected during the machine operation. The sintered getter bodies increase surface area and capacity, requiring less frequent reactivation and facilitating greater overall life of the pump. A discussion of the experimental results in terms of sorption speed and capacity for various gases is presented

  15. α6β1- and αV-integrins are required for long-term self-renewal of murine embryonic stem cells in the absence of LIF.

    Science.gov (United States)

    Cattavarayane, Sandhanakrishnan; Palovuori, Riitta; Tanjore Ramanathan, Jayendrakishore; Manninen, Aki

    2015-02-27

    The growth properties and self-renewal capacity of embryonic stem (ES) cells are regulated by their immediate microenvironment such as the extracellular matrix (ECM). Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear. Here we have studied the effects of different ECM substrates and integrins in mouse ES cells in the absence of Leukemia Inhibitory Factor (LIF) using short-term assays as well as long-term cultures. Removal of LIF from ES cell culture medium induced morphological differentiation of ES cells into polarized epistem cell-like cells. These cells maintained epithelial morphology and expression of key stemness markers for at least 10 passages in the absence of LIF when cultured on laminin, fibronectin or collagen IV substrates. The specific functional roles of α6-, αV- and β1-integrin subunits were dissected using stable lentivirus-mediated RNAi methodology. β1-integrins were required for ES cell survival in long-term cultures and for the maintenance of stem cell marker expression. Inhibition of α6-integrin expression compromised self-renewal on collagen while αV-integrins were required for robust ES cell adhesion on laminin. Analysis of the stemness marker expression revealed subtle differences between α6- and αV-depleted ES cells but the expression of both was required for optimal self-renewal in long-term ES cell cultures. In the absence of LIF, long-term ES cell cultures adapt an epistem cell-like epithelial phenotype and retain the expression of multiple stem cell markers. Long-term maintenance of such self-renewing cultures depends on the expression of β1-, α6- and αV-integrins.

  16. Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus

    Directory of Open Access Journals (Sweden)

    Kahlia Wong

    2014-08-01

    Full Text Available Thymic epithelial cells (TECs are critical for T cell development and self-tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration.

  17. Depletion of Tcf3 and Lef1 maintains mouse embryonic stem cell self-renewal

    OpenAIRE

    Ye, Shoudong; Zhang, Tao; Tong, Chang; Zhou, Xingliang; He, Kan; Ban, Qian; Liu, Dahai; Ying, Qi-Long

    2017-01-01

    ABSTRACT Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1...

  18. The self-renewal signaling pathways utilized by gastric cancer stem cells.

    Science.gov (United States)

    Fu, Ying; Li, Hui; Hao, Xishan

    2017-04-01

    Gastric cancer is a leading cause of cancer-related mortality worldwide. Cancer stem cells are the source of tumor recurrence and metastasis. Self-renewal is a marker of cancer stem cells and also the basis of long-lasting survival and tumor progression. Although the mechanism of gastric cancer stem cell self-renewal is not clear, there are several signaling pathways and environmental factors known to be involved. This mini review describes recent developments in the self-renewal signaling pathway of gastric cancer stem cell research. Advancements made in this field of research will likely support the development of novel therapeutic strategies for gastric cancer.

  19. Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.

    Science.gov (United States)

    Yan, Huaming; Konstorum, Anna; Lowengrub, John S

    2018-05-01

    We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.

  20. Argonaute-2-null embryonic stem cells are retarded in self-renewal ...

    Indian Academy of Sciences (India)

    Present address: Institute of Stem Cells and Regenerative Medicine, Bangalore, India ... [Chandra Shekar P, Naim A, Partha Sarathi D and Kumar S 2011 Argonaute-2-null embryonic stem cells are retarded in self-renewal ..... Research, India.

  1. High Capacity cylinder roller bearing; High Capacity Zylinderrollenlager. Ein vollrolliges Lager mit Kaefig

    Energy Technology Data Exchange (ETDEWEB)

    Reichert, J.; Baum, J. [SKF, Schweinfurt (Germany)

    2007-07-15

    The high capacity cylinder roller bearing is an example for continuous development of SKF products and does an effective contribution to increase operational safety and offers the possibility to reduce weight and compact design. (GL)

  2. Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity

    International Nuclear Information System (INIS)

    Gatti, Monica; Pattarozzi, Alessandra; Bajetto, Adriana; Würth, Roberto; Daga, Antonio; Fiaschi, Pietro; Zona, Gianluigi; Florio, Tullio; Barbieri, Federica

    2013-01-01

    Cancer stem cells (CSCs) or tumor initiating cells (TICs) drive glioblastoma (GBM) development, invasiveness and drug resistance. Distinct molecular pathways might regulate CSC biology as compared to cells in the bulk tumor mass, representing potential therapeutic targets. Chemokine CXCL12 and its receptor CXCR4 control proliferation, invasion and angiogenesis in GBM cell lines and primary cultures, but little is known about their activity in GBM CSCs. We demonstrate that CSCs, isolated from five human GBMs, express CXCR4 and release CXCL12 in vitro, although different levels of expression and secretion were observed in individual cultures, as expected for the heterogeneity of GBMs. CXCL12 treatment induced Akt-mediated significant pro-survival and self-renewal activities, while proliferation was induced at low extent. The role of CXCR4 signaling in CSC survival and self-renewal was further demonstrated using the CXCR4 antagonist AMD3100 that reduced self-renewal and survival with greater efficacy in the cultures that released higher CXCL12 amounts. The specificity of CXCL12 in sustaining CSC survival was demonstrated by the lack of AMD3100-dependent inhibition of viability in differentiated cells derived from the same GBMs. These findings, although performed on a limited number of tumor samples, suggest that the CXCL12/CXCR4 interaction mediates survival and self-renewal in GBM CSCs with high selectivity, thus emerging as a candidate system responsible for maintenance of cancer progenitors, and providing survival benefits to the tumor

  3. Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells

    Directory of Open Access Journals (Sweden)

    Yang Hoon Huh

    2015-03-01

    Full Text Available There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow. Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify such useful and specific DSC biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells, with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ.

  4. wnt3a but not wnt11 supports self-renewal of embryonic stem cells

    International Nuclear Information System (INIS)

    Singla, Dinender K.; Schneider, David J.; LeWinter, Martin M.; Sobel, Burton E.

    2006-01-01

    wnt proteins (wnts) promote both differentiation of midbrain dopaminergic cells and self-renewal of haematopoietic stem cells. Mouse embryonic stem (ES) cells can be maintained and self-renew on mouse feeder cell layers or in media containing leukemia inhibitory factor (LIF). However, the effects of wnts on ES cells self-renewal and differentiation are not clearly understood. In the present study, we found that conditioned medium prepared from L cells expressing wnt3a can replace feeder cell layers and medium containing LIF in maintaining ES cells in the proliferation without differentiation (self-renewal) state. By contrast, conditioned medium from NIH3T3 cells expressing wnt11 did not. Alkaline phosphatase staining and compact colony formation were used as criteria of cells being in the undifferentiated state. ES cells maintained in medium conditioned by Wnt3a expressing cells underwent freezing and thawing while maintaining properties seen with LIF maintained ES cells. Purified wnt3a did not maintain self-renewal of ES cells for prolonged intervals. Thus, other factors in the medium conditioned by wnt3a expressing cells may have contributed to maintenance of ES cells in a self-renewal state. Pluripotency of ES cells was determined with the use of embryoid bodies in vitro. PD98059, a MEK specific inhibitor, promoted the growth of undifferentiated ES cells maintained in conditioned medium from wnt3a expressing cells. By contrast, the P38 MAPK inhibitor SB230580 did not, suggesting a role for the MEK pathway in self-renewal and differentiation of ES cells maintained in the wnt3a cell conditioned medium. Thus, our results show that conditioned medium from wnt3a but not wnt11 expressing cells can maintain ES cells in self-renewal and in a pluripotent state

  5. Endogenous production of fibronectin is required for self-renewal of cultured mouse embryonic stem cells.

    Science.gov (United States)

    Hunt, Geoffrey C; Singh, Purva; Schwarzbauer, Jean E

    2012-09-10

    Pluripotent cells are attached to the extracellular matrix (ECM) as they make cell fate decisions within the stem cell niche. Here we show that the ubiquitous ECM protein fibronectin is required for self-renewal decisions by cultured mouse embryonic stem (mES) cells. Undifferentiated mES cells produce fibronectin and assemble a fibrillar matrix. Increasing the level of substrate fibronectin increased cell spreading and integrin receptor signaling through focal adhesion kinase, while concomitantly inducing the loss of Nanog and Oct4 self-renewal markers. Conversely, reducing fibronectin production by mES cells growing on a feeder-free gelatin substrate caused loss of cell adhesion, decreased integrin signaling, and decreased expression of self-renewal markers. These effects were reversed by providing the cells with exogenous fibronectin, thereby restoring adhesion to the gelatin substrate. Interestingly, mES cells do not adhere directly to the gelatin substrate, but rather adhere indirectly through gelatin-bound fibronectin, which facilitates self-renewal via its effects on cell adhesion. These results provide new insights into the mechanism of regulation of self-renewal by growth on a gelatin-coated surface. The effects of increasing or decreasing fibronectin levels show that self-renewal depends on an intermediate level of cell-fibronectin interactions. By providing cell adhesive signals that can act with other self-renewal factors to maintain mES cell pluripotency, fibronectin is therefore a necessary component of the self-renewal signaling pathway in culture. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1

    Science.gov (United States)

    Ye, Shoudong; Li, Ping; Tong, Chang; Ying, Qi-Long

    2013-01-01

    Mouse embryonic stem cell (mESC) self-renewal can be maintained by activation of the leukaemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (Stat3) signalling pathway or dual inhibition (2i) of glycogen synthase kinase 3 (Gsk3) and mitogen-activated protein kinase kinase (MEK). Several downstream targets of the pathways involved have been identified that when individually overexpressed can partially support self-renewal. However, none of these targets is shared among the involved pathways. Here, we show that the CP2 family transcription factor Tfcp2l1 is a common target in LIF/Stat3- and 2i-mediated self-renewal, and forced expression of Tfcp2l1 can recapitulate the self-renewal-promoting effect of LIF or either of the 2i components. In addition, Tfcp2l1 can reprogram post-implantation epiblast stem cells to naïve pluripotent ESCs. Tfcp2l1 upregulates Nanog expression and promotes self-renewal in a Nanog-dependent manner. We conclude that Tfcp2l1 is at the intersection of LIF- and 2i-mediated self-renewal pathways and plays a critical role in maintaining ESC identity. Our study provides an expanded understanding of the current model of ground-state pluripotency. PMID:23942238

  7. Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a.

    Science.gov (United States)

    Jackson, Jacob T; Shields, Benjamin J; Shi, Wei; Di Rago, Ladina; Metcalf, Donald; Nicola, Nicos A; McCormack, Matthew P

    2017-08-01

    The hematopoietically expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of common lymphoid progenitors (CLPs) to lymphoid lineages. Here, we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation, due to a failure of progenitor expansion. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature progenitors. Transcriptome analysis of Hhex-null Lin - Sca + Kit + cells showed that Hhex deletion leads to derepression of polycomb repressive complex 2 (PRC2) and PRC1 target genes, including the Cdkn2a locus encoding the tumor suppressors p16 Ink 4 a and p19 Arf . Indeed, loss of Cdkn2a restored the capacity of Hhex-null blast colonies to generate myeloid progenitors in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to promote PRC2-mediated Cdkn2a repression to enable continued self-renewal and response to hematopoietic stress. Stem Cells 2017;35:1948-1957. © 2017 AlphaMed Press.

  8. The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis.

    Directory of Open Access Journals (Sweden)

    Stephen N Sansom

    2009-06-01

    Full Text Available Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point to define the cellular networks controlling neural stem cell self-renewal and neurogenesis in stem cells of the developing mouse cerebral cortex. We identified the genomic binding locations of Pax6 in neocortical stem cells during normal development and ascertained the functional significance of genes that we found to be regulated by Pax6, finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis. Notably, we defined a core network regulating neocortical stem cell decision-making in which Pax6 interacts with three other regulators of neurogenesis, Neurog2, Ascl1, and Hes1. Analyses of the biological function of Pax6 in neural stem cells through phenotypic analyses of Pax6 gain- and loss-of-function mutant cortices demonstrated that the Pax6-regulated networks operating in neural stem cells are highly dosage sensitive. Increasing Pax6 levels drives the system towards neurogenesis and basal progenitor cell genesis by increasing expression of a cohort of basal progenitor cell determinants, including the key transcription factor Eomes/Tbr2, and thus towards neurogenesis at the expense of self-renewal. Removing Pax6 reduces cortical stem cell self-renewal by decreasing expression of key cell cycle regulators, resulting in excess early neurogenesis. We find that the relative levels of Pax6, Hes1, and Neurog2 are key determinants of a dynamic network that controls whether neural stem cells self-renew, generate cortical neurons, or generate basal progenitor cells

  9. RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation

    OpenAIRE

    Närvä, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Huha-Pekka; Nästi, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lähdesmäki, Harri; Rao, Anjana; Lahesmaa, Ritta

    2012-01-01

    Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. F...

  10. High Capacity Radio over Fiber Transmission Links

    DEFF Research Database (Denmark)

    Caballero Jambrina, Antonio

    . This achievement has satisfied the requirements on transmission robustness and high capacity of next generation hybrid optical fibre-wireless networks. One important contribution of this thesis is the novel concept of photonic downconversion with free-running pulsed laser source for phase modulated Radio-over-Fiber......This thesis expands the state-of-the-art on the detection of high speed wireless signals using optics. Signal detection at speeds over 1 Gbps at carrier Radio Frequency (RF) ranging from 5 GHz to 100 GHz have been achieved by applying novel concepts on optical digital coherent receivers......-wave frequencies at carrier frequencies exceeding 60 GHz, using photonic baseband technologies. For signal generation, high spectral-efficient optical modulation technologies are used together with optical heterodyning. In the detection side, the mm-wave signal is modulated in the optical domain and received using...

  11. High-capacity neutron activation analysis facility

    International Nuclear Information System (INIS)

    Hochel, R.C.

    1979-01-01

    A high-capacity neutron activation analysis facility, the Reactor Activation Facility, was designed and built and has been in operation for about a year at one of the Savannah River Plant's production reactors. The facility determines uranium and about 19 other trace elements in hydrogeochemical samples collected in the National Uranium Resource Evaluation program. The facility has a demonstrated average analysis rate of over 10,000 samples per month, and a peak rate of over 16,000 samples per month. Uranium is determined by cyclic activation and delayed neutron counting of the U-235 fission products; other elements are determined from gamma-ray spectra recorded in subsequent irradiation, decay, and counting steps. The method relies on the absolute activation technique and is highly automated for round-the-clock unattended operation

  12. Moisture buffering capacity of highly absorbing materials

    Energy Technology Data Exchange (ETDEWEB)

    Cerolini, S.; D' Orazio, M.; Stazi, A. [Department of Architecture, Construction and Structures (DACS), Faculty of Engineering, Polytechnic University of Marche, Via Brecce Bianche, 60100 Ancona (Italy); Di Perna, C. [Department of Energetics, Faculty of Engineering, Polytechnic University of Marche, Via Brecce Bianche, 60100 Ancona (Italy)

    2009-02-15

    This research investigates the possibility to use highly absorbing materials to dampen indoor RH% variations. The practical MBV of sodium polyacrylate, cellulose-based material, perlite and gypsum is evaluated for a daily cyclic exposure that alternates high (75%) and low (33%) RH% levels for 8 h and 16 h, respectively. The adjustment velocity to RH% variations and the presence of hysteretic phenomena are also presented. The cellulose-based material proves to be the most suitable for moisture buffering applications. Starting from this material's properties, the effect of thickness, vapour resistance factor ({mu}) and mass surface exchange coefficient (Z{sub v}) on sorption capacity is evaluated by the use of a numerical model. (author)

  13. High-capacity neutron activation analysis facility

    International Nuclear Information System (INIS)

    Hochel, R.C.; Bowman, W.W.; Zeh, C.W.

    1980-01-01

    A high-capacity neutron activation analysis facility, the Reactor Activation Facility, was designed and built and has been in operation for about a year at one of the Savannah River Plant's production reactors. The facility determines uranium and about 19 other elements in hydrogeochemical samples collected in the National Uranium Resource Evaluation program, which is sponsored and funded by the United States Department of Energy, Grand Junction Office. The facility has a demonstrated average analysis rate of over 10,000 samples per month, and a peak rate of over 16,000 samples per month. Uranium is determined by cyclic activation and delayed neutron counting of the U-235 fission products; other elements are determined from gamma-ray spectra recorded in subsequent irradiation, decay, and counting steps. The method relies on the absolute activation technique and is highly automated for round-the-clock unattended operation

  14. The NASA CSTI High Capacity Power Project

    International Nuclear Information System (INIS)

    Winter, J.; Dudenhoefer, J.; Juhasz, A.; Schwarze, G.; Patterson, R.; Ferguson, D.; Schmitz, P.; Vandersande, J.

    1992-01-01

    This paper describes the elements of NASA's CSTI High Capacity Power Project which include Systems Analysis, Stirling Power Conversion, Thermoelectric Power Conversion, Thermal Management, Power Management, Systems Diagnostics, Environmental Interactions, and Material/Structural Development. Technology advancement in all elements is required to provide the growth capability, high reliability and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall project will develop and demonstrate the technology base required to provide a wide range of modular power systems compatible with the SP-100 reactor which facilitates operation during lunar and planetary day/night cycles as well as allowing spacecraft operation at any attitude or distance from the sun. Significant accomplishments in all of the project elements will be presented, along with revised goals and project timeliness recently developed

  15. Hepatoma SK Hep-1 cells exhibit characteristics of oncogenic mesenchymal stem cells with highly metastatic capacity.

    Directory of Open Access Journals (Sweden)

    Jong Ryeol Eun

    Full Text Available SK Hep-1 cells (SK cells derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity.We found that classical mesenchymal stem cell (MSC markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC and bone marrow-derived MSC (BM-MSC do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC, and that their derivatives also function as CSCs.Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of tumor initiation, development and

  16. The NASA CSTI High Capacity Power Program

    International Nuclear Information System (INIS)

    Winter, J.M.

    1991-09-01

    The SP-100 program was established in 1983 by DOD, DOE, and NASA as a joint program to develop the technology necessary for space nuclear power systems for military and civil applications. During 1986 and 1987, the NASA Advanced Technology Program was responsible for maintaining the momentum of promising technology advancement efforts started during Phase 1 of SP-100 and to strengthen, in key areas, the chances for successful development and growth capability of space nuclear reactor power systems for future space applications. In 1988, the NASA Advanced Technology Program was incorporated into NASA's new Civil Space Technology Initiative (CSTI). The CSTI program was established to provide the foundation for technology development in automation and robotics, information, propulsion, and power. The CSTI High Capacity Power Program builds on the technology efforts of the SP-100 program, incorporates the previous NASA advanced technology project, and provides a bridge to the NASA exploration technology programs. The elements of CSTI high capacity power development include conversion systems: Stirling and thermoelectric, thermal management, power management, system diagnostics, and environmental interactions. Technology advancement in all areas, including materials, is required to provide the growth capability, high reliability, and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall program will develop and demonstrate the technology base required to provide a wide range of modular power systems while minimizing the impact of day/night operations as well as attitudes and distance from the Sun. Significant accomplishments in all of the program elements will be discussed, along with revised goals and project timelines recently developed

  17. Development of high-capacity antimatter storage

    International Nuclear Information System (INIS)

    Howe, Steven D.; Smith, Gerald A.

    2000-01-01

    Space is vast. Over the next few decades, humanity will strive to send probes farther and farther into space to establish long baselines for interferometry, to visit the Kuiper Belt, to identify the heliopause, or to map the Oort cloud. In order to solve many of the mysteries of the universe or to explore the solar system and beyond, one single technology must be developed--high performance propulsion. In essence, future missions to deep space will require specific impulses between 50,000 and 200,000 seconds and energy densities greater than 10 14 j/kg in order to accomplish the mission within the career lifetime of an individual, 40 years. Only two technologies available to mankind offer such performance--fusion and antimatter. Currently envisioned fusion systems are too massive. Alternatively, because of the high energy density, antimatter powered systems may be relatively compact. The single key technology that is required to enable the revolutionary concept of antimatter propulsion is safe, reliable, high-density storage. Under a grant from the NASA Institute of Advanced Concepts, we have identified two potential mechanisms that may enable high capacity antimatter storage systems to be built. We will describe planned experiments to verify the concepts. Development of a system capable of storing megajoules per gram will allow highly instrumented platforms to make fast missions to great distances. Such a development will open the universe to humanity

  18. High Capacity Hydrogen Storage on Nanoporous Biocarbon

    Science.gov (United States)

    Burress, Jacob; Wood, Mikael; Gordon, Michael; Parilla, Phillip; Benham, Michael; Wexler, Carlos; Hawthorne, Fred; Pfeifer, Peter

    2008-03-01

    The Alliance for Collaborative Research in Alternative Fuel Technology (http://all-craft.missouri.edu) has been optimizing nanoporous biocarbon for high capacity hydrogen storage. The hydrogen storage was measured gravimetrically and volumetrically (Sievert's apparatus). These measurements have been validated by NREL and Hiden Isochema. Sample S-33/k, our current best performer, stores 73-91 g H2/kg carbon at 77 K and 47 bar, and 1.0-1.6 g H2/kg carbon at 293 K and 47 bar. Hydrogen isotherms run by Hiden Isochema have given experimental binding energies of 8.8 kJ/mol compared to the binding energy of graphite of 5 kJ/mol. Results from a novel boron doping technique will also be presented. The benefits and validity of using boron-doping on carbon will also be discussed.

  19. Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell, Leading to Bohring-Opitz-like Syndrome in Mice

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2016-06-01

    Full Text Available De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood mortality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models, we found that Asxl1 global loss as well as conditional deletion in osteoblasts and their progenitors led to significant bone loss and a markedly decreased number of bone marrow stromal cells (BMSCs compared with wild-type littermates. Asxl1−/− BMSCs displayed impaired self-renewal and skewed differentiation, away from osteoblasts and favoring adipocytes. RNA-sequencing analysis revealed altered expression of genes involved in cell proliferation, skeletal development, and morphogenesis. Furthermore, gene set enrichment analysis showed decreased expression of stem cell self-renewal gene signature, suggesting a role of Asxl1 in regulating the stemness of BMSCs. Importantly, re-introduction of Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1−/− BMSCs. Our study unveils a pivotal role of ASXL1 in the maintenance of BMSC functions and skeletal development.

  20. Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell, Leading to Bohring-Opitz-like Syndrome in Mice.

    Science.gov (United States)

    Zhang, Peng; Xing, Caihong; Rhodes, Steven D; He, Yongzheng; Deng, Kai; Li, Zhaomin; He, Fuhong; Zhu, Caiying; Nguyen, Lihn; Zhou, Yuan; Chen, Shi; Mohammad, Khalid S; Guise, Theresa A; Abdel-Wahab, Omar; Xu, Mingjiang; Wang, Qian-Fei; Yang, Feng-Chun

    2016-06-14

    De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood mortality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models, we found that Asxl1 global loss as well as conditional deletion in osteoblasts and their progenitors led to significant bone loss and a markedly decreased number of bone marrow stromal cells (BMSCs) compared with wild-type littermates. Asxl1(-/-) BMSCs displayed impaired self-renewal and skewed differentiation, away from osteoblasts and favoring adipocytes. RNA-sequencing analysis revealed altered expression of genes involved in cell proliferation, skeletal development, and morphogenesis. Furthermore, gene set enrichment analysis showed decreased expression of stem cell self-renewal gene signature, suggesting a role of Asxl1 in regulating the stemness of BMSCs. Importantly, re-introduction of Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1(-/-) BMSCs. Our study unveils a pivotal role of ASXL1 in the maintenance of BMSC functions and skeletal development. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Fostering the Self-Renewal of Teachers: An Underutilized Approach to Innovating Interdisciplinary Education

    Directory of Open Access Journals (Sweden)

    David J. Waters

    2013-06-01

    Full Text Available Our goal is to call teachers’ attention to the need for selfrenewal, challenging them to consider it a necessary approach to innovating interdisciplinary education. Our prescription for sustained self-renewal: Each teacher assembles a gallery of intellectual heroes — gifted and articulate thinkers — to serve as their own life-long teachers. In this paper, we share our experience teaching a "skills course" to interdisciplinary graduate students in Purdue University’s Center on Aging and the Life Course. The course, titled "To See and To Seize Opportunities", exposes scholars-in-training to an array of skills and attitudes that foster self-renewal and peak performance. Leading educators must work hard to create better opportunities for self-renewal. By envisioning even our best teachers as unfinished and under construction, we open up a new dialogue situating the self-renewal of teachers at the very core of educational excellence across a broad range of disciplines. To innovate interdisciplinary education, we believe it is time for a curricular re-think, emphasizing the importance of a transdisciplinary skills course in which teachers and their students can explore transformative ideas on personal development and self-renewal — in the classroom together.

  2. Sp5 induces the expression of Nanog to maintain mouse embryonic stem cell self-renewal.

    Science.gov (United States)

    Tang, Ling; Wang, Manman; Liu, Dahai; Gong, Mengting; Ying, Qi-Long; Ye, Shoudong

    2017-01-01

    Activation of signal transducer and activator of transcription 3 (STAT3) by leukemia inhibitory factor (LIF) maintains mouse embryonic stem cell (mESC) self-renewal. Our previous study showed that trans-acting transcription factor 5 (Sp5), an LIF/STAT3 downstream target, supports mESC self-renewal. However, the mechanism by which Sp5 exerts these effects remains elusive. Here, we found that Nanog is a direct target of Sp5 and mediates the self-renewal-promoting effect of Sp5 in mESCs. Overexpression of Sp5 induced Nanog expression, while knockdown or knockout of Sp5 decreased the Nanog level. Moreover, chromatin immunoprecipitation (ChIP) assays showed that Sp5 directly bound to the Nanog promoter. Functional studies revealed that knockdown of Nanog eliminated the mESC self-renewal-promoting ability of Sp5. Finally, we demonstrated that the self-renewal-promoting function of Sp5 was largely dependent on its zinc finger domains. Taken together, our study provides unrecognized functions of Sp5 in mESCs and will expand our current understanding of the regulation of mESC pluripotency.

  3. Porcine spermatogonial stem cells self-renew effectively in a three dimensional culture microenvironment.

    Science.gov (United States)

    Park, Ji Eun; Park, Min Hee; Kim, Min Seong; Park, Yeo Reum; Yun, Jung Im; Cheong, Hee Tae; Kim, Minseok; Choi, Jung Hoon; Lee, Eunsong; Lee, Seung Tae

    2017-12-01

    Generally, self-renewal of spermatogonial stem cells (SSCs) is maintained in vivo in a three-dimensional (3D) microenvironment consisting of the seminiferous tubule basement membrane, indicating the importance of the 3D microenvironment for in vitro culture of SSCs. Here, we report a 3D culture microenvironment that effectively maintains porcine SSC self-renewal during culture. Porcine SSCs were cultured in an agarose-based 3D hydrogel and in 2D culture plates either with or without feeder cells. Subsequently, the effects of 3D culture on the maintenance of undifferentiated SSCs were identified by analyzing cell colony formation and morphology, AP activity, and transcriptional and translational regulation of self-renewal-related genes and the effects on proliferation by analyzing cell viability and single cell-derived colony number. The 3D culture microenvironment constructed using a 0.2% (w/v) agarose-based 3D hydrogel showed the strongest maintenance of porcine SSC self-renewal and induced significant improvements in proliferation compared with 2D culture microenvironments. These results demonstrate that self-renewal of porcine SSCs can be maintained more effectively in a 3D than in a 2D culture microenvironment. Moreover, this will play a significant role in developing novel culture systems for SSCs derived from diverse species in the future, which will contribute to SSC-related research. © 2017 International Federation for Cell Biology.

  4. Trend of telomerase activity change during human iPSC self-renewal and differentiation revealed by a quartz crystal microbalance based assay

    Science.gov (United States)

    Zhou, Yitian; Zhou, Ping; Xin, Yinqiang; Wang, Jie; Zhu, Zhiqiang; Hu, Ji; Wei, Shicheng; Ma, Hongwei

    2014-11-01

    Telomerase plays an important role in governing the life span of cells for its capacity to extend telomeres. As high activity of telomerase has been found in stem cells and cancer cells specifically, various methods have been developed for the evaluation of telomerase activity. To overcome the time-consuming procedures and complicated manipulations of existing methods, we developed a novel method named Telomeric Repeat Elongation Assay based on Quartz crystal microbalance (TREAQ) to monitor telomerase activity during the self-renewal and differentiation of human induced pluripotent stem cells (hiPSCs). TREAQ results indicated hiPSCs possess invariable telomerase activity for 11 passages on Matrigel and a steady decline of telomerase activity when differentiated for different periods, which is confirmed with existing golden standard method. The pluripotency of hiPSCs during differentiation could be estimated through monitoring telomerase activity and compared with the expression levels of markers of pluripotency gene via quantitative real time PCR. Regular assessment for factors associated with pluripotency or stemness was expensive and requires excessive sample consuming, thus TREAQ could be a promising alternative technology for routine monitoring of telomerase activity and estimate the pluripotency of stem cells.

  5. HTR8/SVneo Cells Display Trophoblast Progenitor Cell-Like Characteristics Indicative of Self-Renewal, Repopulation Activity, and Expression of “Stemness-” Associated Transcription Factors

    Directory of Open Access Journals (Sweden)

    Maja Weber

    2013-01-01

    Full Text Available Introduction. JEG3 is a choriocarcinoma—and HTR8/SVneo a transformed extravillous trophoblast—cell line often used to model the physiologically invasive extravillous trophoblast. Past studies suggest that these cell lines possess some stem or progenitor cell characteristics. Aim was to study whether these cells fulfill minimum criteria used to identify stem-like (progenitor cells. In summary, we found that the expression profile of HTR8/SVneo (CDX2+, NOTCH1+, SOX2+, NANOG+, and OCT- is distinct from JEG3 (CDX2+ and NOTCH1+ as seen only in human-serum blocked immunocytochemistry. This correlates with HTR8/SVneo’s self-renewal capacities, as made visible via spheroid formation and multi-passagability in hanging drops protocols paralleling those used to maintain embryoid bodies. JEG3 displayed only low propensity to form and reform spheroids. HTR8/SVneo spheroids migrated to cover and seemingly repopulate human chorionic villi during confrontation cultures with placental explants in hanging drops. We conclude that HTR8/SVneo spheroid cells possess progenitor cell traits that are probably attained through corruption of “stemness-” associated transcription factor networks. Furthermore, trophoblastic cells are highly prone to unspecific binding, which is resistant to conventional blocking methods, but which can be alleviated through blockage with human serum.

  6. HTR8/SVneo cells display trophoblast progenitor cell-like characteristics indicative of self-renewal, repopulation activity, and expression of "stemness-" associated transcription factors.

    Science.gov (United States)

    Weber, Maja; Knoefler, Ilka; Schleussner, Ekkehard; Markert, Udo R; Fitzgerald, Justine S

    2013-01-01

    JEG3 is a choriocarcinoma--and HTR8/SVneo a transformed extravillous trophoblast--cell line often used to model the physiologically invasive extravillous trophoblast. Past studies suggest that these cell lines possess some stem or progenitor cell characteristics. Aim was to study whether these cells fulfill minimum criteria used to identify stem-like (progenitor) cells. In summary, we found that the expression profile of HTR8/SVneo (CDX2+, NOTCH1+, SOX2+, NANOG+, and OCT-) is distinct from JEG3 (CDX2+ and NOTCH1+) as seen only in human-serum blocked immunocytochemistry. This correlates with HTR8/SVneo's self-renewal capacities, as made visible via spheroid formation and multi-passagability in hanging drops protocols paralleling those used to maintain embryoid bodies. JEG3 displayed only low propensity to form and reform spheroids. HTR8/SVneo spheroids migrated to cover and seemingly repopulate human chorionic villi during confrontation cultures with placental explants in hanging drops. We conclude that HTR8/SVneo spheroid cells possess progenitor cell traits that are probably attained through corruption of "stemness-" associated transcription factor networks. Furthermore, trophoblastic cells are highly prone to unspecific binding, which is resistant to conventional blocking methods, but which can be alleviated through blockage with human serum.

  7. Building the UPPA high capacity tensiometer

    Directory of Open Access Journals (Sweden)

    Mendes Joao

    2016-01-01

    Full Text Available High capacity tensiometers (HCTs are sensors capable of directly measuring tensile pore water pressure (suction in soils. HCTs are typically composed of a casing that encapsulates a high air entry value ceramic filter, a water reservoir and a pressure sensing element. Since the creation of the first HCT by Ridley and Burland in 1993 at Imperial College London, HCTs have been almost exclusively built and used in academic research. The limited use in industrial applications can be explained by a lack of unsaturated soil mechanics knowledge among engineering practitioners but also by the technical difficulties associated to the direct measurement of tensile water pressures beyond the cavitation limit of -100kPa. In this paper, we present the recent design and manufacture of a new HCT at the Université de Pau et des Pays de l’Adour (UPPA in France. Different prototypes were tried by changing the main components of the device including the type of ceramic filter, pressure transducer and geometry of the external casing. In particular, two ceramic filters of distinct porosity, three pressure transducers with distinct materials/geometries and four casing designs were tested.

  8. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation.

    Science.gov (United States)

    Wang, Kui; Zhang, Tao; Dong, Qiang; Nice, Edouard Collins; Huang, Canhua; Wei, Yuquan

    2013-03-14

    Stem cells are characterized by their unique ability of self-renewal to maintain the so-called stem cell pool. Over the past decades, reactive oxygen species (ROS) have been recognized as toxic aerobic metabolism byproducts that are harmful to stem cells, leading to DNA damage, senescence or cell death. Recently, a growing body of literature has shown that stem cells reside in redox niches with low ROS levels. The balance of Redox homeostasis facilitates stem cell self-renewal by an intricate network. Thus, to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, it is critical to address the important role of redox homeostasis in the regulation of self-renewal and differentiation of stem cells. In this regard, we will discuss the regulatory mechanisms involved in the subtly orchestrated balance of redox status in stem cells by scavenger antioxidant enzyme systems that are well monitored by the hypoxia niches and crucial redox regulators including forkhead homeobox type O family (FoxOs), apurinic/apyrimidinic (AP) endonuclease1/redox factor-1 (APE1/Ref-1), nuclear factor erythroid-2-related factor 2 (Nrf2) and ataxia telangiectasia mutated (ATM). We will also introduce several pivotal ROS-sensitive molecules, such as hypoxia-inducible factors, p38 mitogen-activated protein kinase (p38) and p53, involved in the redox-regulated stem cell self-renewal. Specifically, all the aforementioned molecules can act as 'redox sensors' by virtue of redox modifications of their cysteine residues, which are critically important in the control of protein function. Given the importance of redox homeostasis in the regulation of stem cell self-renewal, understanding the underlying molecular mechanisms involved will provide important new insights into stem cell biology.

  9. Evaluating the immortal strand hypothesis in cancer stem cells: symmetric/self-renewal as the relevant surrogate marker of tumorigenicity.

    Science.gov (United States)

    Winquist, Raymond J; Hall, Amy B; Eustace, Brenda K; Furey, Brinley F

    2014-09-15

    Stem cells subserve repair functions for the lifetime of the organism but, as a consequence of this responsibility, are candidate cells for accumulating numerous genetic and/or epigenetic aberrations leading to malignant transformation. However, given the importance of this guardian role, stem cells likely harbor some process for maintaining their precious genetic code such as non-random segregation of chromatid strands as predicted by the Immortal Strand Hypothesis (ISH). Discerning such non-random chromosomal segregation and asymmetric cell division in normal or cancer stem cells has been complicated by methodological shortcomings but also by differing division kinetics amongst tissues and the likelihood that both asymmetric and symmetric cell divisions, dictated by local extrinsic factors, are operant in these cells. Recent data suggest that cancer stem cells demonstrate a higher incidence of symmetric versus asymmetric cell division with both daughter cells retaining self-renewal characteristics, a profile which may underlie poorly differentiated morphology and marked clonal diversity in tumors. Pathways and targets are beginning to emerge which may provide opportunities for preventing such a predilection in cancer stem cells and that will hopefully translate into new classes of chemotherapeutics in oncology. Thus, although the existence of the ISH remains controversial, the shift of cell division dynamics to symmetric random chromosome segregation/self-renewal, which would negate any likelihood of template strand retention, appears to be a surrogate marker for the presence of highly malignant tumorigenic cell populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Xihang Chen

    2018-01-01

    Full Text Available Autophagy is a highly conserved cellular process that degrades modified, surplus, or harmful cytoplasmic components by sequestering them in autophagosomes which then fuses with the lysosome for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis, as well as for remodeling during normal development. Impairment of this process has been implicated in various diseases, in the pathogenic response to bacterial and viral infections, and in aging. Pluripotent stem cells, with their ability to self-replicate and to give rise to any specialized cell type, are very valuable resources for cell-based medical therapies and open a number of promising avenues for studying human development and disease. It has been suggested that autophagy is vital for the maintenance of cellular homeostasis in stem cells, and subsequently more in-depth knowledge about the regulation of autophagy in stem cell biology has been acquired recently. In this review, we describe the most significant advances in the understanding of autophagy regulation in hematopoietic and mesenchymal stem cells, as well as in induced pluripotent stem cells. In particular, we highlight the roles of various autophagy activities in the regulation of self-renewal and differentiation of these stem cells.

  11. Dermal Contributions to Human Interfollicular Epidermal Architecture and Self-Renewal

    Directory of Open Access Journals (Sweden)

    Kynan T. Lawlor

    2015-11-01

    Full Text Available The human interfollicular epidermis is renewed throughout life by populations of proliferating basal keratinocytes. Though interfollicular keratinocyte stem cells have been identified, it is not known how self-renewal in this compartment is spatially organized. At the epidermal-dermal junction, keratinocytes sit atop a heterogeneous mix of dermal cells that may regulate keratinocyte self-renewal by influencing local tissue architecture and signalling microenvironments. Focusing on the rete ridges and complementary dermal papillae in human skin, we review the identity and organisation of abundant dermal cells types and present evidence for interactions between the dermal microenvironment and the interfollicular keratinocytes.

  12. Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Huang, Sheng-Dong; Yuan, Yang; Liu, Xiao-Hong; Gong, De-Jun; Bai, Chen-Guang; Wang, Feng; Luo, Jun-Hui; Xu, Zhi-Yun

    2009-01-01

    p75 NTR has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75 NTR in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75 NTR+ cells. p75 NTR expression in ESCC was assessed by immunohistochemistry. p75 NTR+ and p75 NTR- cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75 NTR+ and p75 NTR- cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay, 64 copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75 NTR+ cells. In ESCC specimens, p75 NTR was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75 NTR+ cells was 1.6%–3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75 NTR+ cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75 NTR+ cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75 NTR+ cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, β1-integrin and β4-integrin, were lower in p75 NTR+ cells. In addition, p75 NTR+ cells generated both p75 NTR+ and p75 NTR- cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75 NTR+ cells were found to be more resistant to DDP and exhibited lower 64 copper accumulation than p75 NTR- cells. Our results demonstrated that p75 NTR+ cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75 NTR+ cells may probably be attributable to

  13. Towards green high capacity optical networks

    Science.gov (United States)

    Glesk, I.; Mohd Warip, M. N.; Idris, S. K.; Osadola, T. B.; Andonovic, I.

    2011-09-01

    The demand for fast, secure, energy efficient high capacity networks is growing. It is fuelled by transmission bandwidth needs which will support among other things the rapid penetration of multimedia applications empowering smart consumer electronics and E-businesses. All the above trigger unparallel needs for networking solutions which must offer not only high-speed low-cost "on demand" mobile connectivity but should be ecologically friendly and have low carbon footprint. The first answer to address the bandwidth needs was deployment of fibre optic technologies into transport networks. After this it became quickly obvious that the inferior electronic bandwidth (if compared to optical fiber) will further keep its upper hand on maximum implementable serial data rates. A new solution was found by introducing parallelism into data transport in the form of Wavelength Division Multiplexing (WDM) which has helped dramatically to improve aggregate throughput of optical networks. However with these advancements a new bottleneck has emerged at fibre endpoints where data routers must process the incoming and outgoing traffic. Here, even with the massive and power hungry electronic parallelism routers today (still relying upon bandwidth limiting electronics) do not offer needed processing speeds networks demands. In this paper we will discuss some novel unconventional approaches to address network scalability leading to energy savings via advance optical signal processing. We will also investigate energy savings based on advanced network management through nodes hibernation proposed for Optical IP networks. The hibernation reduces the network overall power consumption by forming virtual network reconfigurations through selective nodes groupings and by links segmentations and partitionings.

  14. The development and application of high-capacity thickening techniques

    International Nuclear Information System (INIS)

    Ji Zhenwan; Song Yuejie

    1995-01-01

    On the basis of sedimentation theory and comparison between the high-capacity and conventional thickening techniques, the authors analyse the ways to increase capacity and to improve technological parameters of thickeners, describes the construction features, development, application, automatic control and test installations of high-capacity thickeners at home and abroad

  15. Establishing long-term cultures with self-renewing acute myeloid leukemia stem/progenitor cells

    NARCIS (Netherlands)

    van Gosliga, Djoke; Schepers, Hein; Rizo, Aleksandra; van der Kolk, Dorina; Vellenga, Edo; Schuringa, Jan Jacob

    2007-01-01

    Objective. With the emergence of the concept of the leukemia stem cell, assays to study them remain pivotal in understanding (leukemic) stem cell biology. Methods. We have cultured acute myeloid leukemia CD34(+) cells on bone marrow stroma. Long-term expansion was monitored and self-renewal was

  16. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem

  17. Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm

    DEFF Research Database (Denmark)

    Hamilton, William B; Brickman, Joshua M

    2014-01-01

    Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification, we explored...

  18. New insights into redox regulation of stem cell self-renewal and differentiation.

    Science.gov (United States)

    Ren, Fenglian; Wang, Kui; Zhang, Tao; Jiang, Jingwen; Nice, Edouard Collins; Huang, Canhua

    2015-08-01

    Reactive oxygen species (ROS), the natural byproducts of aerobic metabolism, are precisely orchestrated to evoke diverse signaling pathways. To date, studies have focused mainly on the detrimental effects of ROS in stem cells. Recently, accumulating evidence has suggested that ROS also function as second messengers that modulate stem cell self-renewal and differentiation by regulating intricate signaling networks. Although many efforts have been made to clarify the general effects of ROS on signal transduction in stem cells, less is known about the initial and direct executors of ROS signaling, which are known as 'redox sensors'. Modifications of cysteine residues in redox sensors are of significant importance in the modulation of protein function in response to different redox conditions. Intriguingly, most key molecules in ROS signaling and cell cycle regulation (including transcriptional factors and kinases) that are crucial in the regulation of stem cell self-renewal and differentiation have the potential to be redox sensors. We highlight herein the importance of redox regulation of these key regulators in stem cell self-renewal and differentiation. Understanding the mechanisms of redox regulation in stem cell self-renewal and differentiation will open exciting new perspectives for stem cell biology. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Protein Kinase-A Inhibition Is Sufficient to Support Human Neural Stem Cells Self-Renewal.

    Science.gov (United States)

    Georges, Pauline; Boissart, Claire; Poulet, Aurélie; Peschanski, Marc; Benchoua, Alexandra

    2015-12-01

    Human pluripotent stem cell-derived neural stem cells offer unprecedented opportunities for producing specific types of neurons for several biomedical applications. However, to achieve it, protocols of production and amplification of human neural stem cells need to be standardized, cost effective, and safe. This means that small molecules should progressively replace the use of media containing cocktails of protein-based growth factors. Here we have conducted a phenotypical screening to identify pathways involved in the regulation of hNSC self-renewal. We analyzed 80 small molecules acting as kinase inhibitors and identified compounds of the 5-isoquinolinesulfonamide family, described as protein kinase A (PKA) and protein kinase G inhibitors, as candidates to support hNSC self-renewal. Investigating the mode of action of these compounds, we found that modulation of PKA activity was central in controlling the choice between self-renewal or terminal neuronal differentiation of hNSC. We finally demonstrated that the pharmacological inhibition of PKA using the small molecule HA1004 was sufficient to support the full derivation, propagation, and long-term maintenance of stable hNSC in absence of any other extrinsic signals. Our results indicated that tuning of PKA activity is a core mechanism regulating hNSC self-renewal and differentiation and delineate the minimal culture media requirement to maintain undifferentiated hNSC in vitro. © 2015 AlphaMed Press.

  20. Fine-tuning Hematopoiesis: Microenvironmental factors regulating self-renewal and differentiation of hematopoietic stem cells

    NARCIS (Netherlands)

    T.C. Luis (Tiago)

    2010-01-01

    markdownabstract__Abstract__ Hematopoietic stem cells (HSCs) have the ability to self renew and generate all lineages of blood cells. Although it is currently well established that hematopoietic stem cells (HSCs) regenerate the blood compartment, it was only in the 1960s that was introduced the

  1. FOXO3 Promotes Quiescence in Adult Muscle Stem Cells during the Process of Self-Renewal

    Directory of Open Access Journals (Sweden)

    Suchitra D. Gopinath

    2014-04-01

    Full Text Available Skeletal muscle stem cells, or “satellite cells” (SCs, are required for the regeneration of damaged muscle tissue. Although SCs self-renew during regeneration, the mechanisms that govern SC re-entry into quiescence remain elusive. We show that FOXO3, a member of the forkhead family of transcription factors, is expressed in quiescent SCs (QSCs. Conditional deletion of Foxo3 in QSCs impairs self-renewal and increases the propensity of SCs to adopt a differentiated fate. Transcriptional analysis of SCs lacking FOXO3 revealed a downregulation of Notch signaling, a key regulator of SC quiescence. Conversely, overexpression of Notch intracellular domain (NICD rescued the self-renewal deficit of FOXO3-deficient SCs. We show that FOXO3 regulates NOTCH1 and NOTCH3 receptor expression and that decreasing expression of NOTCH1 and NOTCH3 receptors phenocopies the effect of FOXO3 deficiency in SCs. We demonstrate that FOXO3, perhaps by activating Notch signaling, promotes the quiescent state during SC self-renewal in adult muscle regeneration.

  2. [Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro].

    Science.gov (United States)

    Peng, Li; Li, Fu-Xi; Shao, Wen-Feng; Xiong, Jing-Bo

    2013-10-01

    To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms. Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR. TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres. TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.

  3. Environmental oxygen tension regulates the energy metabolism and self-renewal of human embryonic stem cells.

    Science.gov (United States)

    Forristal, Catherine E; Christensen, David R; Chinnery, Fay E; Petruzzelli, Raffaella; Parry, Kate L; Sanchez-Elsner, Tilman; Houghton, Franchesca D

    2013-01-01

    Energy metabolism is intrinsic to cell viability but surprisingly has been little studied in human embryonic stem cells (hESCs). The current study aims to investigate the effect of environmental O2 tension on carbohydrate utilisation of hESCs. Highly pluripotent hESCs cultured at 5% O2 consumed significantly more glucose, less pyruvate and produced more lactate compared to those maintained at 20% O2. Moreover, hESCs cultured at atmospheric O2 levels expressed significantly less OCT4, SOX2 and NANOG than those maintained at 5% O2. To determine whether this difference in metabolism was a reflection of the pluripotent state, hESCs were cultured at 5% O2 in the absence of FGF2 for 16 hours leading to a significant reduction in the expression of SOX2. In addition, these cells consumed less glucose and produced significantly less lactate compared to those cultured in the presence of FGF2. hESCs maintained at 5% O2 were found to consume significantly less O2 than those cultured in the absence of FGF2, or at 20% O2. GLUT1 expression correlated with glucose consumption and using siRNA and chromatin immunoprecipitation was found to be directly regulated by hypoxia inducible factor (HIF)-2α at 5% O2. In conclusion, highly pluripotent cells associated with hypoxic culture consume low levels of O2, high levels of glucose and produce large amounts of lactate, while at atmospheric conditions glucose consumption and lactate production are reduced and there is an increase in oxidative metabolism. These data suggest that environmental O2 regulates energy metabolism and is intrinsic to the self-renewal of hESCs.

  4. Battery designs with high capacity anode materials and cathode materials

    Energy Technology Data Exchange (ETDEWEB)

    Masarapu, Charan; Anguchamy, Yogesh Kumar; Han, Yongbong; Deng, Haixia; Kumar, Sujeet; Lopez, Herman A.

    2017-10-03

    Improved high energy capacity designs for lithium ion batteries are described that take advantage of the properties of high specific capacity anode active compositions and high specific capacity cathode active compositions. In particular, specific electrode designs provide for achieving very high energy densities. Furthermore, the complex behavior of the active materials is used advantageously in a radical electrode balancing design that significantly reduced wasted electrode capacity in either electrode when cycling under realistic conditions of moderate to high discharge rates and/or over a reduced depth of discharge.

  5. A high capacity FASTBUS multiple event buffer

    International Nuclear Information System (INIS)

    Appel, J.A.; Farr, W.D.; Kaplan, D.M.; Levit, L.B.; Napier, T.M.

    1985-01-01

    We have developed a front-end data acquisition and event buffering memory. This single-width FASTBUS module has a capacity of 256K X 32 bits plus parity. The module is dual ported, and its front panel ECLport accepts data at up to 20 MB/sec. It may also be written to and read from as a standard FASTBUS Slave. The module records events as variable length records. Each record is accepted or rejected via front panel control signal. Circuitry to automate FASTBUS record readout and record skip is provided. In its ''linear'' mode, the module may be used as a single pass list. Alternatively, in the ''circular'' mode, the module's internal read pointer can follow its write pointer continuously around the memory. Circular mode is well suited to handling of a continuous data stream. Modules may be linked for larger memory capacity

  6. The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression.

    Science.gov (United States)

    Heiden, Katherine B; Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Wang, Yimin; Liu, Dingxie; Xing, Mingzhao; Prinz, Richard A; Xu, Xiulong

    2014-11-01

    Cancer stem cells (CSCs) have been recently identified in thyroid neoplasm. Anaplastic thyroid cancer (ATC) contains a higher percentage of CSCs than well-differentiated thyroid cancer. The signaling pathways and the transcription factors that regulate thyroid CSC self-renewal remain poorly understood. The objective of this study is to use two ATC cell lines (KAT-18 and SW1736) as a model to study the role of the sonic hedgehog (Shh) pathway in maintaining thyroid CSC self-renewal and to understand its underlying molecular mechanisms. The expression and activity of aldehyde dehydrogenase (ALDH), a marker for thyroid CSCs, was analyzed by Western blot and ALDEFLUOR assay, respectively. The effect of three Shh pathway inhibitors (cyclopamine, HhAntag, GANT61), Shh, Gli1, Snail knockdown, and Gli1 overexpression on thyroid CSC self-renewal was analyzed by ALDEFLUOR assay and thyrosphere formation. The sensitivity of transfected KAT-18 cells to radiation was evaluated by a colony survival assay. Western blot analysis revealed that ALDH protein levels in five thyroid cancer cell lines (WRO82, a follicular thyroid cancer cell line; BCPAP and TPC1, two papillary thyroid cancer cell lines; KAT-18 and SW1736, two ATC cell lines) correlated with the percentage of the ALDH(High) cells as well as Gli1 and Snail expression. The Shh pathway inhibitors, Shh and Gli1 knockdown, in KAT-18 cells decreased thyroid CSC self-renewal and increased radiation sensitivity. In contrast, Gli1 overexpression led to increased thyrosphere formation, an increased percentage of ALDH(High) cells, and increased radiation resistance in KAT-18 cells. Inhibition of the Shh pathway by three specific inhibitors led to decreased Snail expression and a decreased number of ALDH(High) cells in KAT-18 and SW1736. Snail gene knockdown decreased the number of ALDH(High) cells in KAT-18 and SW1736 cells. The Shh pathway promotes the CSC self-renewal in ATC cell lines by Gli1-induced Snail expression.

  7. Developing Leadership Capacity in Others: An Examination of High School Principals' Personal Capacities for Fostering Leadership

    Science.gov (United States)

    Huggins, Kristin Shawn; Klar, Hans W.; Hammonds, Hattie L.; Buskey, Frederick C.

    2017-01-01

    In this multisite case study, we examine the personal capacities of six high school principals who have developed the leadership capacities of other leaders in their respective schools. Participants were purposefully selected by two teams of researchers in two states of the United States, one on the east coast and one on the west coast, who…

  8. Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis.

    Science.gov (United States)

    Cui, Qi; Yang, Su; Ye, Peng; Tian, E; Sun, Guoqiang; Zhou, Jiehua; Sun, Guihua; Liu, Xiaoxuan; Chen, Chao; Murai, Kiyohito; Zhao, Chunnian; Azizian, Krist T; Yang, Lu; Warden, Charles; Wu, Xiwei; D'Apuzzo, Massimo; Brown, Christine; Badie, Behnam; Peng, Ling; Riggs, Arthur D; Rossi, John J; Shi, Yanhong

    2016-02-03

    Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.

  9. New cancer diagnostics and therapeutics from a ninth 'hallmark of cancer': symmetric self-renewal by mutated distributed stem cells.

    Science.gov (United States)

    Sherley, James L

    2013-11-01

    A total of eight cellular alterations associated with human carcinogenesis have been framed as the 'hallmarks of cancer'. This representation overlooks a ninth hallmark of cancer: the requirement for tumor-originating distributed stem cells to shift sufficiently from asymmetric to symmetric self-renewal kinetics for attainment of the high cell production rate necessary to form clinically significant tumors within a human lifespan. Overlooking this ninth hallmark costs opportunities for discovery of more selective molecular targets for development of improved cancer therapeutics and missing cancer stem cell biomarkers of greater specificity. Here, the biological basis for the ninth hallmark of cancer is considered toward highlighting its importance in human carcinogenesis and, as such, its potential for revealing unique molecules for targeting cancer diagnostics and therapeutics.

  10. Activin pathway enhances colorectal cancer stem cell self-renew and tumor progression.

    Science.gov (United States)

    Liu, Rui; Wang, Jun-Hua; Xu, Chengxiong; Sun, Bo; Kang, Sa-Ouk

    2016-10-28

    Activin belongs to transforming growth factor (TGF)-β super family of growth and differentiation factors and activin pathway participated in broad range of cell process. Studies elaborated activin pathway maintain pluripotency in human stem cells and suggest that the function of activin/nodal signaling in self-renew would be conserved across embryonic and adult stem cells. In this study, we tried to determine the effect of activin signaling pathway in regulation of cancer stem cells as a potential target for cancer therapy in clinical trials. A population of colorectal cancer cells was selected by the treatment of activin A. This population of cell possessed stem cell character with sphere formation ability. We demonstrated activin pathway enhanced the colorectal cancer stem cells self-renew and contribute to colorectal cancer progression in vivo. Targeting activin pathway potentially provide effective strategy for colorectal cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Hedi ePeterson

    2013-10-01

    Full Text Available Pluripotency in human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs is regulated by three transcription factors - OCT3/4, SOX2 and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behaviour of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11 and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

  12. The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation

    Directory of Open Access Journals (Sweden)

    Pavan Rajanahalli

    2015-01-01

    Full Text Available Silver nanoparticles (AgNPs are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.

  13. Leptin and Adiponectin Modulate the Self-renewal of Normal Human Breast Epithelial Stem Cells.

    Science.gov (United States)

    Esper, Raymond M; Dame, Michael; McClintock, Shannon; Holt, Peter R; Dannenberg, Andrew J; Wicha, Max S; Brenner, Dean E

    2015-12-01

    Multiple mechanisms are likely to account for the link between obesity and increased risk of postmenopausal breast cancer. Two adipokines, leptin and adiponectin, are of particular interest due to their opposing biologic functions and associations with breast cancer risk. In the current study, we investigated the effects of leptin and adiponectin on normal breast epithelial stem cells. Levels of leptin in human adipose explant-derived conditioned media positively correlated with the size of the normal breast stem cell pool. In contrast, an inverse relationship was found for adiponectin. Moreover, a strong linear relationship was observed between the leptin/adiponectin ratio in adipose conditioned media and breast stem cell self-renewal. Consistent with these findings, exogenous leptin stimulated whereas adiponectin suppressed breast stem cell self-renewal. In addition to local in-breast effects, circulating factors, including leptin and adiponectin, may contribute to the link between obesity and breast cancer. Increased levels of leptin and reduced amounts of adiponectin were found in serum from obese compared with age-matched lean postmenopausal women. Interestingly, serum from obese women increased stem cell self-renewal by 30% compared with only 7% for lean control serum. Taken together, these data suggest a plausible explanation for the obesity-driven increase in postmenopausal breast cancer risk. Leptin and adiponectin may function as both endocrine and paracrine/juxtacrine factors to modulate the size of the normal stem cell pool. Interventions that disrupt this axis and thereby normalize breast stem cell self-renewal could reduce the risk of breast cancer. ©2015 American Association for Cancer Research.

  14. Endogenous production of fibronectin is required for self-renewal of cultured mouse embryonic stem cells

    OpenAIRE

    Hunt, Geoffrey C.; Singh, Purva; Schwarzbauer, Jean E.

    2012-01-01

    Pluripotent cells are attached to the extracellular matrix (ECM) as they make cell fate decisions within the stem cell niche. Here we show that the ubiquitous ECM protein fibronectin is required for self-renewal decisions by cultured mouse embryonic stem (mES) cells. Undifferentiated mES cells produce fibronectin and assemble a fibrillar matrix. Increasing the level of substrate fibronectin increased cell spreading and integrin receptor signaling through focal adhesion kinase, while concomita...

  15. Dual role of BMP signaling in the regulation of Drosophila intestinal stem cell self-renewal.

    Science.gov (United States)

    Tian, Aiguo; Jiang, Jin

    2017-10-02

    Many adult organs including Drosophila adult midguts rely on resident stem cells to replenish damaged cells during tissue homeostasis and regeneration. Previous studies have shown that, upon injury, intestinal stem cells (ISCs) in the midguts can increase proliferation and lineage differentiation to meet the demand for tissue repair. Our recent study has demonstrated that, in response to certain injury, midguts can expand ISC population size as an additional regenerative mechanism. We found that injury elicited by bleomycin feeding or bacterial infection increased the production of two BMP ligands (Dpp and Gbb) in enterocytes (ECs), leading to elevated BMP signaling in progenitor cells that drove an expansion of ISCs by promoting their symmetric self-renewing division. Interestingly, we also found that BMP signaling in ECs inhibits the production of Dpp and Gbb, and that this negative feedback mechanism is required to reset ISC pool size to the homeostatic state. Our findings suggest that BMP signaling exerts two opposing influences on stem cell activity depending on where it acts: BMP signaling in progenitor cells promotes ISC self-renewal while BMP signaling in ECs restricts ISC self-renewal by preventing excessive production of BMP ligands. Our results further suggest that transient expansion of ISC population in conjunction with increasing ISC proliferation provides a more effective strategy for tissue regeneration.

  16. High-Capacity, High-Voltage Composite Oxide Cathode Materials

    Science.gov (United States)

    Hagh, Nader M.

    2015-01-01

    This SBIR project integrates theoretical and experimental work to enable a new generation of high-capacity, high-voltage cathode materials that will lead to high-performance, robust energy storage systems. At low operating temperatures, commercially available electrode materials for lithium-ion (Li-ion) batteries do not meet energy and power requirements for NASA's planned exploration activities. NEI Corporation, in partnership with the University of California, San Diego, has developed layered composite cathode materials that increase power and energy densities at temperatures as low as 0 degC and considerably reduce the overall volume and weight of battery packs. In Phase I of the project, through innovations in the structure and morphology of composite electrode particles, the partners successfully demonstrated an energy density exceeding 1,000 Wh/kg at 4 V at room temperature. In Phase II, the team enhanced the kinetics of Li-ion transport and electronic conductivity at 0 degC. An important feature of the composite cathode is that it has at least two components that are structurally integrated. The layered material is electrochemically inactive; however, upon structural integration with a spinel material, the layered material can be electrochemically activated and deliver a large amount of energy with stable cycling.

  17. Capacity Bounds and High-SNR Capacity of MIMO Intensity-Modulation Optical Channels

    KAUST Repository

    Chaaban, Anas

    2018-02-19

    The capacity of the intensity modulation direct detection multiple-input multiple-output channel is studied. Therein, the nonnegativity constraint of the transmit signal limits the applicability of classical schemes, including precoding. Thus, new ways are required for deriving capacity bounds for this channel. To this end, capacity lower bounds are developed in this paper by deriving the achievable rates of two precodingfree schemes: Channel inversion and QR decomposition. The achievable rate of a DC-offset SVD-based scheme is also derived as a benchmark. Then, capacity upper bounds are derived and compared against the lower bounds. As a result, the capacity at high signal-to-noise ratio (SNR) is characterized for the case where the number of transmit apertures is not larger than the number of receive apertures, and is shown to be achievable by the QR decomposition scheme. This is shown for a channel with average intensity or peak intensity constraints. Under both constraints, the high-SNR capacity is approximated within a small gap. Extensions to a channel with more transmit apertures than receive apertures are discussed, and capacity bounds for this case are derived.

  18. Capacity Bounds and High-SNR Capacity of MIMO Intensity-Modulation Optical Channels

    KAUST Repository

    Chaaban, Anas; Rezki, Zouheir; Alouini, Mohamed-Slim

    2018-01-01

    The capacity of the intensity modulation direct detection multiple-input multiple-output channel is studied. Therein, the nonnegativity constraint of the transmit signal limits the applicability of classical schemes, including precoding. Thus, new ways are required for deriving capacity bounds for this channel. To this end, capacity lower bounds are developed in this paper by deriving the achievable rates of two precodingfree schemes: Channel inversion and QR decomposition. The achievable rate of a DC-offset SVD-based scheme is also derived as a benchmark. Then, capacity upper bounds are derived and compared against the lower bounds. As a result, the capacity at high signal-to-noise ratio (SNR) is characterized for the case where the number of transmit apertures is not larger than the number of receive apertures, and is shown to be achievable by the QR decomposition scheme. This is shown for a channel with average intensity or peak intensity constraints. Under both constraints, the high-SNR capacity is approximated within a small gap. Extensions to a channel with more transmit apertures than receive apertures are discussed, and capacity bounds for this case are derived.

  19. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells

    Science.gov (United States)

    Kobayashi, Hideki; Butler, Jason M.; O'Donnell, Rebekah; Kobayashi, Mariko; Ding, Bi-Sen; Bonner, Bryant; Chiu, Vi K.; Nolan, Daniel J.; Shido, Koji; Benjamin, Laura; Rafii, Shahin

    2010-01-01

    Endothelial cells establish an instructive vascular niche that reconstitutes haematopoietic stem and progenitor cells (HSPCs) through release of specific paracrine growth factors, known as angiocrine factors. However, the mechanism by which endothelial cells balance the rate of proliferation and lineage-specific differentiation of HSPCs is unknown. Here, we demonstrate that Akt activation in endothelial cells, through recruitment of mTOR, but not the FoxO pathway, upregulates specific angiocrine factors that support expansion of CD34−Flt3− KLS HSPCs with long-term haematopoietic stem cell (LT-HSC) repopulation capacity. Conversely, co-activation of Akt-stimulated endothelial cells with p42/44 MAPK shifts the balance towards maintenance and differentiation of the HSPCs. Selective activation of Akt1 in the endothelial cells of adult mice increased the number of colony forming units in the spleen and CD34−Flt3− KLS HSPCs with LT-HSC activity in the bone marrow, accelerating haematopoietic recovery. Therefore, the activation state of endothelial cells modulates reconstitution of HSPCs through the upregulation of angiocrine factors, with Akt–mTOR-activated endothelial cells supporting the self-renewal of LT-HSCs and expansion of HSPCs, whereas MAPK co-activation favours maintenance and lineage-specific differentiation of HSPCs. PMID:20972423

  20. High capacity anode materials for lithium ion batteries

    Science.gov (United States)

    Lopez, Herman A.; Anguchamy, Yogesh Kumar; Deng, Haixia; Han, Yongbon; Masarapu, Charan; Venkatachalam, Subramanian; Kumar, Suject

    2015-11-19

    High capacity silicon based anode active materials are described for lithium ion batteries. These materials are shown to be effective in combination with high capacity lithium rich cathode active materials. Supplemental lithium is shown to improve the cycling performance and reduce irreversible capacity loss for at least certain silicon based active materials. In particular silicon based active materials can be formed in composites with electrically conductive coatings, such as pyrolytic carbon coatings or metal coatings, and composites can also be formed with other electrically conductive carbon components, such as carbon nanofibers and carbon nanoparticles. Additional alloys with silicon are explored.

  1. High visual working memory capacity in trait social anxiety.

    Science.gov (United States)

    Moriya, Jun; Sugiura, Yoshinori

    2012-01-01

    Working memory capacity is one of the most important cognitive functions influencing individual traits, such as attentional control, fluid intelligence, and also psychopathological traits. Previous research suggests that anxiety is associated with impaired cognitive function, and studies have shown low verbal working memory capacity in individuals with high trait anxiety. However, the relationship between trait anxiety and visual working memory capacity is still unclear. Considering that people allocate visual attention more widely to detect danger under threat, visual working memory capacity might be higher in anxious people. In the present study, we show that visual working memory capacity increases as trait social anxiety increases by using a change detection task. When the demand to inhibit distractors increased, however, high visual working memory capacity diminished in individuals with social anxiety, and instead, impaired filtering of distractors was predicted by trait social anxiety. State anxiety was not correlated with visual working memory capacity. These results indicate that socially anxious people could potentially hold a large amount of information in working memory. However, because of an impaired cognitive function, they could not inhibit goal-irrelevant distractors and their performance decreased under highly demanding conditions.

  2. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors.

    Science.gov (United States)

    Janssens, Derek H; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

    2014-03-01

    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

  3. Albumin-associated lipids regulate human embryonic stem cell self-renewal.

    Directory of Open Access Journals (Sweden)

    Francesc R Garcia-Gonzalo

    Full Text Available BACKGROUND: Although human embryonic stem cells (hESCs hold great promise as a source of differentiated cells to treat several human diseases, many obstacles still need to be surmounted before this can become a reality. First among these, a robust chemically-defined system to expand hESCs in culture is still unavailable despite recent advances in the understanding of factors controlling hESC self-renewal. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we attempted to find new molecules that stimulate long term hESC self-renewal. In order to do this, we started from the observation that a commercially available serum replacement product has a strong positive effect on the expansion of undifferentiated hESCs when added to a previously reported chemically-defined medium. Subsequent experiments demonstrated that the active ingredient within the serum replacement is lipid-rich albumin. Furthermore, we show that this activity is trypsin-resistant, strongly suggesting that lipids and not albumin are responsible for the effect. Consistent with this, lipid-poor albumin shows no detectable activity. Finally, we identified the major lipids bound to the lipid-rich albumin and tested several lipid candidates for the effect. CONCLUSIONS/SIGNIFICANCE: Our discovery of the role played by albumin-associated lipids in stimulating hESC self-renewal constitutes a significant advance in the knowledge of how hESC pluripotency is maintained by extracellular factors and has important applications in the development of increasingly chemically defined hESC culture systems.

  4. High-capacity nanocarbon anodes for lithium-ion batteries

    International Nuclear Information System (INIS)

    Zhang, Haitao; Sun, Xianzhong; Zhang, Xiong; Lin, He; Wang, Kai; Ma, Yanwei

    2015-01-01

    Highlights: • The nanocarbon anodes in lithium-ion batteries deliver a high capacity of ∼1100 mA h g −1 . • The nanocarbon anodes exhibit excellent cyclic stability. • A novel structure of carbon materials, hollow carbon nanoboxes, has potential application in lithium-ion batteries. - Abstract: High energy and power density of secondary cells like lithium-ion batteries become much more important in today’s society. However, lithium-ion battery anodes based on graphite material have theoretical capacity of 372 mA h g −1 and low charging-discharging rate. Here, we report that nanocarbons including mesoporous graphene (MPG), carbon tubular nanostructures (CTN), and hollow carbon nanoboxes (HCB) are good candidate for lithium-ion battery anodes. The nanocarbon anodes have high capacity of ∼1100, ∼600, and ∼500 mA h g −1 at 0.1 A g −1 for MPG, CTN, and HCB, respectively. The capacity of 181, 141, and 139 mA h g −1 at 4 A g −1 for MPG, CTN, and HCB anodes is retained. Besides, nanocarbon anodes show high cycling stability during 1000 cycles, indicating formation of a passivating layer—solid electrolyte interphase, which support long-term cycling. Nanocarbons, constructed with graphene layers which fulfill lithiation/delithiation process, high ratio of graphite edge structure, and high surface area which facilitates capacitive behavior, deliver high capacity and improved rate-capability

  5. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling

    Science.gov (United States)

    Wang, Linlin; Schulz, Thomas C.; Sherrer, Eric S.; Dauphin, Derek S.; Shin, Soojung; Nelson, Angelique M.; Ware, Carol B.; Zhan, Mei; Song, Chao-Zhong; Chen, Xiaoji; Brimble, Sandii N.; McLean, Amanda; Galeano, Maria J.; Uhl, Elizabeth W.; D'Amour, Kevin A.; Chesnut, Jonathan D.; Rao, Mahendra S.

    2007-01-01

    Despite progress in developing defined conditions for human embryonic stem cell (hESC) cultures, little is known about the cell-surface receptors that are activated under conditions supportive of hESC self-renewal. A simultaneous interrogation of 42 receptor tyrosine kinases (RTKs) in hESCs following stimulation with mouse embryonic fibroblast (MEF) conditioned medium (CM) revealed rapid and prominent tyrosine phosphorylation of insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R); less prominent tyrosine phosphorylation of epidermal growth factor receptor (EGFR) family members, including ERBB2 and ERBB3; and trace phosphorylation of fibroblast growth factor receptors. Intense IGF1R and IR phosphorylation occurred in the absence of MEF conditioning (NCM) and was attributable to high concentrations of insulin in the proprietary KnockOut Serum Replacer (KSR). Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, while disruption of ERBB2 signaling with the selective inhibitor AG825 severely inhibited hESC proliferation and promoted apoptosis. A simple defined medium containing an IGF1 analog, heregulin-1β (a ligand for ERBB2/ERBB3), fibroblast growth factor-2 (FGF2), and activin A supported long-term growth of multiple hESC lines. These studies identify previously unappreciated RTKs that support hESC proliferation and self-renewal, and provide a rationally designed medium for the growth and maintenance of pluripotent hESCs. PMID:17761519

  6. YAP1 Regulates OCT4 Activity and SOX2 Expression to Facilitate Self-Renewal and Vascular Mimicry of Stem-Like Cells.

    Science.gov (United States)

    Bora-Singhal, Namrata; Nguyen, Jonathan; Schaal, Courtney; Perumal, Deepak; Singh, Sandeep; Coppola, Domenico; Chellappan, Srikumar

    2015-06-01

    Non-small cell lung cancer (NSCLC) is highly correlated with smoking and has very low survival rates. Multiple studies have shown that stem-like cells contribute to the genesis and progression of NSCLC. Our results show that the transcriptional coactivator yes-associated protein 1 (YAP1), which is the oncogenic component of the Hippo signaling pathway, is elevated in the stem-like cells from NSCLC and contributes to their self-renewal and ability to form angiogenic tubules. Inhibition of YAP1 by a small molecule or depletion of YAP1 by siRNAs suppressed self-renewal and vascular mimicry of stem-like cells. These effects of YAP1 were mediated through the embryonic stem cell transcription factor, Sox2. YAP1 could transcriptionally induce Sox2 through a physical interaction with Oct4; Sox2 induction occurred independent of TEAD2 transcription factor, which is the predominant mediator of YAP1 functions. The binding of Oct4 to YAP1 could be detected in cell lines as well as tumor tissues; the interaction was elevated in NSCLC samples compared to normal tissue as seen by proximity ligation assays. YAP1 bound to Oct4 through the WW domain, and a peptide corresponding to this region could disrupt the interaction. Delivery of the WW domain peptide to stem-like cells disrupted the interaction and abrogated Sox2 expression, self-renewal, and vascular mimicry. Depleting YAP1 reduced the expression of multiple epithelial-mesenchymal transition genes and prevented the growth and metastasis of tumor xenografts in mice; overexpression of Sox2 in YAP1 null cells rescued these functions. These results demonstrate a novel regulation of stem-like functions by YAP1, through the modulation of Sox2 expression. © 2015 AlphaMed Press.

  7. The p53 inhibitor, pifithrin-{alpha}, suppresses self-renewal of embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Abdelalim, Essam Mohamed, E-mail: essam_abdelalim@yahoo.com [Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan); Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522 (Egypt); Tooyama, Ikuo [Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192 (Japan)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer We determine the role of p53 in ES cells under unstressful conditions. Black-Right-Pointing-Pointer PFT-{alpha} suppresses ES cell proliferation. Black-Right-Pointing-Pointer PFT-{alpha} induces ES cell cycle arrest. Black-Right-Pointing-Pointer PFT-{alpha} downregulates Nanog and cyclin D1. -- Abstract: Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-{alpha}, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-{alpha} resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-{alpha} caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.

  8. Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal

    Science.gov (United States)

    Chandrakesan, Parthasarathy; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Taylor, Vivian E.; Li, James D.; Ali, Naushad; Sureban, Sripathi M.; Qante, Michael; Wang, Timothy C.; Bronze, Michael S.; Houchen, Courtney W.

    2015-01-01

    To date, no discrete genetic signature has been defined for isolated Dclk1+ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1+ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1+ cells, we FACS-sorted Dclk1+ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1-CreER;Rosa26-YFP). Analysis of sorted YFP+ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP− cells. Dclk1+ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1+ population. A significant increase in self-renewal capability (14-fold) was observed in in vitro isolated Dclk1+ cells. The unique genetic report presented in this manuscript suggests that Dclk1+ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1+ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells. PMID:26362399

  9. Alternative Splicing of MBD2 Supports Self-Renewal in Human Pluripotent Stem Cells

    Science.gov (United States)

    Lu, Yu; Loh, Yuin-Han; Li, Hu; Cesana, Marcella; Ficarro, Scott B.; Parikh, Jignesh R.; Salomonis, Nathan; Toh, Cheng-Xu Delon; Andreadis, Stelios T.; Luckey, C. John; Collins, James J.; Daley, George Q.; Marto, Jarrod A.

    2014-01-01

    Summary Alternative RNA splicing (AS) regulates proteome diversity, including isoform-specific expression of several pluripotency genes. Here, we integrated global gene expression and proteomic analyses and identified a molecular signature suggesting a central role for AS in maintaining human pluripotent stem cell (hPSC) self-renewal. We demonstrate the splicing factor SFRS2 is an OCT4 target gene required for pluripotency. SFRS2 regulates AS of the methyl-CpG-binding protein MBD2, whose isoforms play opposing roles in maintenance of, and reprogramming to, pluripotency. While both MDB2a and MBD2c are enriched at the OCT4 and NANOG promoters, MBD2a preferentially interacts with repressive NuRD chromatin remodeling factors and promotes hPSC differentiation, whereas overexpression of MBD2c enhances reprogramming of fibroblasts to pluripotency. The miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and MDB2a. These data suggest that OCT4, SFRS2, and MBD2 participate in a positive feedback loop, regulating proteome diversity complexity in support of hPSC self-renewal and reprogramming. PMID:24813856

  10. The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells

    International Nuclear Information System (INIS)

    Abdelalim, Essam Mohamed; Tooyama, Ikuo

    2012-01-01

    Highlights: ► We determine the role of p53 in ES cells under unstressful conditions. ► PFT-α suppresses ES cell proliferation. ► PFT-α induces ES cell cycle arrest. ► PFT-α downregulates Nanog and cyclin D1. -- Abstract: Recent studies have reported the role of p53 in suppressing the pluripotency of embryonic stem (ES) cells after DNA damage and blocking the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. However, to date no evidence has been presented to support the function of p53 in unstressed ES cells. In this study, we investigated the effect of pifithrin (PFT)-α, an inhibitor of p53-dependent transcriptional activation, on self-renewal of ES cells. Our results revealed that treatment of ES cells with PFT-α resulted in the inhibition of ES cell propagation in a dose-dependent manner, as indicated by a marked reduction in the cell number and colony size. Also, PFT-α caused a cell cycle arrest and significant reduction in DNA synthesis. In addition, inhibition of p53 activity reduced the expression levels of cyclin D1 and Nanog. These findings indicate that p53 pathway in ES cells rather than acting as an inactive gene, is required for ES cell proliferation and self-renewal under unstressful conditions.

  11. Adult hematopoietic stem cells lacking Hif-1α self-renew normally

    Science.gov (United States)

    Vukovic, Milica; Sepulveda, Catarina; Subramani, Chithra; Guitart, Amélie V.; Mohr, Jasmine; Allen, Lewis; Panagopoulou, Theano I.; Paris, Jasmin; Lawson, Hannah; Villacreces, Arnaud; Armesilla-Diaz, Alejandro; Gezer, Deniz; Holyoake, Tessa L.; Ratcliffe, Peter J.

    2016-01-01

    The hematopoietic stem cell (HSC) pool is maintained under hypoxic conditions within the bone marrow microenvironment. Cellular responses to hypoxia are largely mediated by the hypoxia-inducible factors, Hif-1 and Hif-2. The oxygen-regulated α subunits of Hif-1 and Hif-2 (namely, Hif-1α and Hif-2α) form dimers with their stably expressed β subunits and control the transcription of downstream hypoxia-responsive genes to facilitate adaptation to low oxygen tension. An initial study concluded that Hif-1α is essential for HSC maintenance, whereby Hif-1α–deficient HSCs lost their ability to self-renew in serial transplantation assays. In another study, we demonstrated that Hif-2α is dispensable for cell-autonomous HSC maintenance, both under steady-state conditions and following transplantation. Given these unexpected findings, we set out to revisit the role of Hif-1α in cell-autonomous HSC functions. Here we demonstrate that inducible acute deletion of Hif-1α has no impact on HSC survival. Notably, unstressed HSCs lacking Hif-1α efficiently self-renew and sustain long-term multilineage hematopoiesis upon serial transplantation. Finally, Hif-1α–deficient HSCs recover normally after hematopoietic injury induced by serial administration of 5-fluorouracil. We therefore conclude that despite the hypoxic nature of the bone marrow microenvironment, Hif-1α is dispensable for cell-autonomous HSC maintenance. PMID:27060169

  12. KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not Pluripotency

    Directory of Open Access Journals (Sweden)

    Diwash Acharya

    2017-04-01

    Full Text Available Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5 lysine acetyltransferase (KAT, which is essential for embryonic stem cell (ESC self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function in differentiation. Consistent with this phenotype, KAT-deficient mouse embryos exhibited post-implantation developmental defects. These findings establish separable KAT-dependent and KAT-independent functions of Tip60 in ESCs and during differentiation, revealing a complex repertoire of regulatory functions for this essential chromatin remodeling complex.

  13. Differential Radiosensitizing Effect of Valproic Acid in Differentiation Versus Self-Renewal Promoting Culture Conditions

    International Nuclear Information System (INIS)

    Debeb, Bisrat G.; Xu Wei; Mok, Henry; Li Li; Robertson, Fredika; Ueno, Naoto T.; Reuben, Jim; Lucci, Anthony; Cristofanilli, Massimo; Woodward, Wendy A.

    2010-01-01

    Purpose: It has been shown that valproic acid (VA) enhances the proliferation and self-renewal of normal hematopoietic stem cells and that breast cancer stem/progenitor cells can be resistant to radiation. From these data, we hypothesized that VA would fail to radiosensitize breast cancer stem/progenitor cells grown to three-dimensional (3D) mammospheres. Methods and Materials: We used the MCF7 breast cancer cell line grown under stem cell-promoting culture conditions (3D mammosphere) and standard nonstem cell monolayer culture conditions (two-dimensional) to examine the effect of pretreatment with VA on radiation sensitivity in clonogenic survival assays and on the expression of embryonic stem cell transcription factors. Results: 3D-cultured MCF-7 cells expressed higher levels of Oct4, Nanog, and Sox2. The 3D passage enriched self-renewal and increased radioresistance in the 3D mammosphere formation assays. VA radiosensitized adherent cells but radioprotected 3D cells in single-fraction clonogenic assays. Moreover, fractionated radiation sensitized VA-treated adherent MCF7 cells but did not have a significant effect on VA-treated single cells grown to mammospheres. Conclusion: We have concluded that VA might preferentially radiosensitize differentiated cells compared with those expressing stem cell surrogates and that stem cell-promoting culture is a useful tool for in vitro evaluation of novel cancer therapeutic agents and radiosensitizers.

  14. Expression dynamics of self-renewal factors for spermatogonial stem cells in the mouse testis.

    Science.gov (United States)

    Sakai, Mizuki; Masaki, Kaito; Aiba, Shota; Tone, Masaaki; Takashima, Seiji

    2018-04-16

    Glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are bona fide self-renewal factors for spermatogonial stem cells (SSCs). Although GDNF is indispensable for the maintenance of SSCs, the role of FGF2 in the testis remains to be elucidated. To clarify this, the expression dynamics and regulatory mechanisms of Fgf2 and Gdnf in the mouse testes were analyzed. It is well known that Sertoli cells express Gdnf, and its receptor is expressed in a subset of undifferentiated spermatogonia, including SSCs. However, we found that Fgf2 was mainly expressed in the germ cells and its receptors were expressed not only in the cultured spermatogonial cell line, but also in testicular somatic cells. Aging, hypophysectomy, retinoic acid treatment, and testicular injury induced distinct Fgf2 and Gdnf expression dynamics, suggesting a difference in the expression mechanism of Fgf2 and Gdnf in the testis. Such differences might cause a dynamic fluctuation of Gdnf/Fgf2 ratio depending on the intrinsic/extrinsic cues. Considering that FGF2-cultured spermatogonia exhibit more differentiated phenotype than those cultured with GDNF, FGF2 might play a role distinct from that of GDNF in the testis, despite the fact that both factors are self-renewal factor for SSC in vitro.

  15. Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling.

    Science.gov (United States)

    Stoyanova, Tanya; Goldstein, Andrew S; Cai, Houjian; Drake, Justin M; Huang, Jiaoti; Witte, Owen N

    2012-10-15

    The cell surface protein Trop2 is expressed on immature stem/progenitor-like cells and is overexpressed in many epithelial cancers. However the biological function of Trop2 in tissue maintenance and tumorigenesis remains unclear. In this study, we demonstrate that Trop2 is a regulator of self-renewal, proliferation, and transformation. Trop2 controls these processes through a mechanism of regulated intramembrane proteolysis that leads to cleavage of Trop2, creating two products: the extracellular domain and the intracellular domain. The intracellular domain of Trop2 is released from the membrane and accumulates in the nucleus. Heightened expression of the Trop2 intracellular domain promotes stem/progenitor self-renewal through signaling via β-catenin and is sufficient to initiate precursor lesions to prostate cancer in vivo. Importantly, we demonstrate that loss of β-catenin or Trop2 loss-of-function cleavage mutants abrogates Trop2-driven self-renewal and hyperplasia in the prostate. These findings suggest that heightened expression of Trop2 is selected for in epithelial cancers to enhance the stem-like properties of self-renewal and proliferation. Defining the mechanism of Trop2 function in self-renewal and transformation is essential to identify new therapeutic strategies to block Trop2 activation in cancer.

  16. ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.

    Science.gov (United States)

    Xing, Yang; Ge, Yuqing; Liu, Chanjuan; Zhang, Xiaobiao; Jiang, Jianhai; Wei, Yuanyan

    2016-06-14

    Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.

  17. Two distinct mechanisms silence chinmo in Drosophila neuroblasts and neuroepithelial cells to limit their self-renewal.

    Science.gov (United States)

    Dillard, Caroline; Narbonne-Reveau, Karine; Foppolo, Sophie; Lanet, Elodie; Maurange, Cédric

    2018-01-25

    Whether common principles regulate the self-renewing potential of neural stem cells (NSCs) throughout the developing central nervous system is still unclear. In the Drosophila ventral nerve cord and central brain, asymmetrically dividing NSCs, called neuroblasts (NBs), progress through a series of sequentially expressed transcription factors that limits self-renewal by silencing a genetic module involving the transcription factor Chinmo. Here, we find that Chinmo also promotes neuroepithelium growth in the optic lobe during early larval stages by boosting symmetric self-renewing divisions while preventing differentiation. Neuroepithelium differentiation in late larvae requires the transcriptional silencing of chinmo by ecdysone, the main steroid hormone, therefore allowing coordination of neural stem cell self-renewal with organismal growth. In contrast, chinmo silencing in NBs is post-transcriptional and does not require ecdysone. Thus, during Drosophila development, humoral cues or tissue-intrinsic temporal specification programs respectively limit self-renewal in different types of neural progenitors through the transcriptional and post-transcriptional regulation of the same transcription factor. © 2018. Published by The Company of Biologists Ltd.

  18. SC1 Promotes MiR124-3p Expression to Maintain the Self-Renewal of Mouse Embryonic Stem Cells by Inhibiting the MEK/ERK Pathway.

    Science.gov (United States)

    Wei, Qing; Liu, Hongliang; Ai, Zhiying; Wu, Yongyan; Liu, Yingxiang; Shi, Zhaopeng; Ren, Xuexue; Guo, Zekun

    2017-01-01

    Self-renewal is one of the most important features of embryonic stem (ES) cells. SC1 is a small molecule modulator that effectively maintains the self-renewal of mouse ES cells in the absence of leukemia inhibitory factor (LIF), serum and feeder cells. However, the mechanism by which SC1 maintains the undifferentiated state of mouse ES cells remains unclear. In this study, microarray and small RNA deep-sequencing experiments were performed on mouse ES cells treated with or without SC1 to identify the key genes and microRNAs that contributed to self-renewal. SC1 regulates the expressions of pluripotency and differentiation factors, and antagonizes the retinoic acid (RA)-induced differentiation in the presence or absence of LIF. SC1 inhibits the MEK/ERK pathway through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and pathway reporting experiments. Small RNA deep-sequencing revealed that SC1 significantly modulates the expression of multiple microRNAs with crucial functions in ES cells. The expression of miR124-3p is upregulated in SC1-treated ES cells, which significantly inhibits the MEK/ERK pathway by targeting Grb2, Sos2 and Egr1. SC1 enhances the self-renewal capacity of mouse ES cells by modulating the expression of key regulatory genes and pluripotency-associated microRNAs. SC1 significantly upregulates miR124-3p expression to further inhibit the MEK/ ERK pathway by targeting Grb2, Sos2 and Egr1. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. HPV16-E2 protein modifies self-renewal and differentiation rate in progenitor cells of human immortalized keratinocytes.

    Science.gov (United States)

    Domínguez-Catzín, Victoria; Reveles-Espinoza, Alicia-María; Sánchez-Ramos, Janet; Cruz-Cadena, Raúl; Lemus-Hernández, Diana; Garrido, Efraín

    2017-04-03

    Cervical cancer is the fourth cause of death worldwide by cancer in women and is a disease associated to persistent infection with human papillomavirus (HPV), particularly from two high-risk types HPV16 and 18. The virus initiates its replicative cycle infecting cells located in the basal layer of the epithelium, where a small population of epithelial stem cells is located performing important functions of renewal and maintenance of the tissue. Viral E2 gene is one of the first expressed after infection and plays relevant roles in the replicative cycle of the virus, modifying fundamental processes in the infected cells. Thus, the aim of the present study was to demonstrate the presence of hierarchic subpopulations in HaCaT cell line and evaluate the effect of HPV16-E2 expression, on their biological processes. HaCaT-HPV16-E2 cells were generated by transduction of HaCaT cell line with a lentiviral vector. The α6-integrin-CD71 expression profile was established by immunostaining and flow cytometric analysis. After sorting, cell subpopulations were analyzed in biological assays for self-renewal, clonogenicity and expression of stemness factors (RT-qPCR). We identified in HaCaT cell line three different subpopulations that correspond to early differentiated cells (α6-integrin dim ), transitory amplifying cells (α6-integrin bri /CD71 bri ) and progenitor cells (α6-integrin bri /CD71 dim ). The last subpopulation showed stem cell characteristics, such as self-renewal ability, clonogenicity and expression of the well-known stem cell factors SOX2, OCT4 and NANOG, suggesting they are stem-like cells. Interestingly, the expression of HPV16-E2 in HaCaT cells changed its α6-integrin-CD71 immunophenotype modifying the relative abundance of the cell subpopulations, reducing significantly the percentage of α6-integrin bri /CD71 dim cells. Moreover, the expression of the stem cell markers was also modified, increasing the expression of SOX2 and NANOG, but decreasing notably

  20. Layered double hydroxide nanoparticles promote self-renewal of mouse embryonic stem cells through the PI3K signaling pathway

    Science.gov (United States)

    Wu, Youjun; Zhu, Rongrong; Zhou, Yang; Zhang, Jun; Wang, Wenrui; Sun, Xiaoyu; Wu, Xianzheng; Cheng, Liming; Zhang, Jing; Wang, Shilong

    2015-06-01

    Embryonic stem cells (ESCs) hold great potential for regenerative medicine due to their two unique characteristics: self-renewal and pluripotency. Several groups of nanoparticles have shown promising applications in directing the stem cell fate. Herein, we investigated the cellular effects of layered double hydroxide nanoparticles (LDH NPs) on mouse ESCs (mESCs) and the associated molecular mechanisms. Mg-Al-LDH NPs with an average diameter of ~100 nm were prepared by hydrothermal methods. To determine the influences of LDH NPs on mESCs, cellular cytotoxicity, self-renewal, differentiation potential, and the possible signaling pathways were explored. Evaluation of cell viability, lactate dehydrogenase release, ROS generation and apoptosis demonstrated the low cytotoxicity of LDH NPs. The alkaline phosphatase activity and the expression of pluripotency genes in mESCs were examined, which indicated that exposure to LDH NPs could support self-renewal and inhibit spontaneous differentiation of mESCs under feeder-free culture conditions. The self-renewal promotion was further proved to be independent of the leukemia inhibitory factor (LIF). Furthermore, cells treated with LDH NPs maintained the potential to differentiate into all three germ layers both in vitro and in vivo through formation of embryoid bodies and teratomas. In addition, we observed that LDH NPs initiated the activation of the PI3K/Akt pathway, while treatment with the PI3K inhibitor LY294002 could block the effects of LDH NPs on mESCs. The results confirmed that the promotion of self-renewal by LDH NPs was associated with activation of the PI3K/Akt signaling pathway. Altogether, our studies identified a new role of LDH NPs in maintaining self-renewal of mouse ES cells which could potentially be applied in stem cell research.Embryonic stem cells (ESCs) hold great potential for regenerative medicine due to their two unique characteristics: self-renewal and pluripotency. Several groups of nanoparticles

  1. Aerobic Capacities of Early College High School Students

    Science.gov (United States)

    Loflin, Jerry W.

    2014-01-01

    The Early College High School Initiative (ECHSI) was introduced in 2002. Since 2002, limited data, especially student physical activity data, have been published pertaining to the ECHSI. The purpose of this study was to examine the aerobic capacities of early college students and compare them to state and national averages. Early college students…

  2. Immortal DNA strand cosegregation requires p53/IMPDH-dependent asymmetric self-renewal associated with adult stem cells.

    Science.gov (United States)

    Rambhatla, Lakshmi; Ram-Mohan, Sumati; Cheng, Jennifer J; Sherley, James L

    2005-04-15

    Because they are long-lived and cycle continuously, adult stem cells (ASCs) are predicted as the most common precursor for cancers in adult mammalian tissues. Two unique attributes have been proposed to restrict the carcinogenic potential of ASCs. These are asymmetric self-renewal that limits their number and immortal DNA strand cosegregation that limits their accumulation of mutations due to DNA replication errors. Until recently, the molecular basis and regulation of these important ASC-specific functions were unknown. We developed engineered cultured cells that exhibit asymmetric self-renewal and immortal DNA strand cosegregation. These model cells were used to show that both ASC-specific functions are regulated by the p53 cancer gene. Previously, we proposed that IMP dehydrogenase (IMPDH) was an essential factor for p53-dependent asymmetric self-renewal. We now confirm this proposal and provide quantitative evidence that asymmetric self-renewal is acutely sensitive to even modest changes in IMPDH expression. These analyses reveal that immortal DNA strand cosegregation is also regulated by IMPDH and confirm the original implicit precept that immortal DNA strand cosegregation is specific to cells undergoing asymmetric self-renewal (i.e., ASCs). With IMPDH being the rate-determining enzyme for guanine ribonucleotide (rGNP) biosynthesis, its requirement implicates rGNPs as important regulators of ASC asymmetric self-renewal and immortal DNA strand cosegregation. An in silico analysis of global gene expression data from human cancer cell lines underscored the importance of p53-IMPDH-rGNP regulation for normal tissue cell kinetics, providing further support for the concept that ASCs are key targets for adult tissue carcinogenesis.

  3. Enhanced Hematopoietic Stem Cell Self-Renewal-Promoting Ability of Clonal Primary Mesenchymal Stromal/Stem cells Versus Their Osteogenic Progeny.

    Science.gov (United States)

    He, Qiling; Scott Swindle, Claude; Wan, Chao; Flynn, Robert J; Oster, Robert A; Chen, Dongquan; Zhang, Fengjie; Shu, Yinglan; Klug, Christopher A

    2017-02-01

    Long-term self-renewing hematopoietic stem cell (LT-HSC) homeostasis within the bone marrow (BM) of adult mammals is regulated by complex interactions between LT-HSC and a number of niche-associated cell types including mesenchymal stromal/stem cells (MSC), osteoblasts (OB), macrophage, and neuronal cells in close proximity with the vasculature. Here, we cloned and functionally characterized a murine BM MSC subpopulation that was uniformly Nestin + Lepr + Sca-1 + CD146 + and could be stably propagated with high colony-forming unit fibroblast re-cloning efficiency. MSC synergized with SCF and IL-11 to support a 20-fold expansion in true LT-HSC after 10-days of in vitro coculture. Optimal stimulation of LT-HSC expansion was minimally dependent on Notch signaling but was significantly enhanced by global inhibition of Wnt signaling. The self-renewal-promoting activity of MSC was progressively lost when MSC clones were differentiated into mature OB. This suggests that the stage of osteoblast development may significantly impact the ability of osteolineage cells to support LT-HSC homeostasis in vivo. Stem Cells 2017;35:473-484. © 2016 AlphaMed Press.

  4. Seeding of single hemopoietic stem cells and self renewal of committed stem cells

    International Nuclear Information System (INIS)

    Brecher, G.

    1986-01-01

    Single cells and two to five proliferating cells were transfused into mice whose own stem cells had been killed by irradiation. When a small inoculum of 50,000 AB marrow cells was given only 4 of 20 recipients survived, but all 4 had only PGK A enzyme in their peripheral blood cells. The results indicate that the survivors received a single pluripotential stem cell capable of proliferating. Survivors showed no deterioration in their blood picture after many months. It was concluded that there is no clonal succession in the marrow cells. Further studies with transfusions of 100,000 and 10,000,000 marrow cells after lethal irradiation suggest that there is production of committed stem cells with significant self-renewal

  5. Recycling rice husks for high-capacity lithium battery anodes.

    Science.gov (United States)

    Jung, Dae Soo; Ryou, Myung-Hyun; Sung, Yong Joo; Park, Seung Bin; Choi, Jang Wook

    2013-07-23

    The rice husk is the outer covering of a rice kernel and protects the inner ingredients from external attack by insects and bacteria. To perform this function while ventilating air and moisture, rice plants have developed unique nanoporous silica layers in their husks through years of natural evolution. Despite the massive amount of annual production near 10(8) tons worldwide, so far rice husks have been recycled only for low-value agricultural items. In an effort to recycle rice husks for high-value applications, we convert the silica to silicon and use it for high-capacity lithium battery anodes. Taking advantage of the interconnected nanoporous structure naturally existing in rice husks, the converted silicon exhibits excellent electrochemical performance as a lithium battery anode, suggesting that rice husks can be a massive resource for use in high-capacity lithium battery negative electrodes.

  6. Higher 5-hydroxymethylcytosine identifies immortal DNA strand chromosomes in asymmetrically self-renewing distributed stem cells.

    Science.gov (United States)

    Huh, Yang Hoon; Cohen, Justin; Sherley, James L

    2013-10-15

    Immortal strands are the targeted chromosomal DNA strands of nonrandom sister chromatid segregation, a mitotic chromosome segregation pattern unique to asymmetrically self-renewing distributed stem cells (DSCs). By nonrandom segregation, immortal DNA strands become the oldest DNA strands in asymmetrically self-renewing DSCs. Nonrandom segregation of immortal DNA strands may limit DSC mutagenesis, preserve DSC fate, and contribute to DSC aging. The mechanisms responsible for specification and maintenance of immortal DNA strands are unknown. To discover clues to these mechanisms, we investigated the 5-methylcytosine and 5-hydroxymethylcytosine (5hmC) content on chromosomes in mouse hair follicle DSCs during nonrandom segregation. Although 5-methylcytosine content did not differ significantly, the relative content of 5hmC was significantly higher in chromosomes containing immortal DNA strands than in opposed mitotic chromosomes containing younger mortal DNA strands. The difference in relative 5hmC content was caused by the loss of 5hmC from mortal chromosomes. These findings implicate higher 5hmC as a specific molecular determinant of immortal DNA strand chromosomes. Because 5hmC is an intermediate during DNA demethylation, we propose a ten-eleven translocase enzyme mechanism for both the specification and maintenance of nonrandomly segregated immortal DNA strands. The proposed mechanism reveals a means by which DSCs "know" the generational age of immortal DNA strands. The mechanism is supported by molecular expression data and accounts for the selection of newly replicated DNA strands when nonrandom segregation is initiated. These mechanistic insights also provide a possible basis for another characteristic property of immortal DNA strands, their guanine ribonucleotide dependency.

  7. Gab2 promotes hematopoietic stem cell maintenance and self-renewal synergistically with STAT5.

    Directory of Open Access Journals (Sweden)

    Geqiang Li

    2010-02-01

    Full Text Available Grb2-associated binding (Gab adapter proteins play major roles in coordinating signaling downstream of hematopoietic cytokine receptors. In hematopoietic cells, Gab2 can modulate phosphatidylinositol-3 kinase and mitogen associated protein kinase activities and regulate the long-term multilineage competitive repopulating activity of hematopoietic stem cells (HSCs. Gab2 may also act in a linear pathway upstream or downstream of signal transducer and activator of transcription-5 (STAT5, a major positive regulator of HSC function. Therefore, we aimed to determine whether Gab2 and STAT5 function in hematopoiesis in a redundant or non-redundant manner.To do this we generated Gab2 mutant mice with heterozygous and homozygous deletions of STAT5. In heterozygous STAT5 mutant mice, deficiencies in HSC/multipotent progenitors were reflected by decreased long-term repopulating activity. This reduction in repopulation function was mirrored in the reduced growth response to early-acting cytokines from sorted double mutant c-Kit(+Lin(-Sca-1(+ (KLS cells. Importantly, in non-ablated newborn mice, the host steady-state engraftment ability was impaired by loss of Gab2 in heterozygous STAT5 mutant background. Fetal liver cells isolated from homozygous STAT5 mutant mice lacking Gab2 showed significant reduction in HSC number (KLS CD150(+CD48(-, reduced HSC survival, and dramatic loss of self-renewal potential as measured by serial transplantation.These data demonstrate new functions for Gab2 in hematopoiesis in a manner that is non-redundant with STAT5. Furthermore, important synergy between STAT5 and Gab2 was observed in HSC self-renewal, which might be exploited to optimize stem cell-based therapeutics.

  8. Self-renewing Monolayer of Primary Colonic or Rectal Epithelial CellsSummary

    Directory of Open Access Journals (Sweden)

    Yuli Wang

    2017-07-01

    Full Text Available Background & Aims: Three-dimensional organoid culture has fundamentally changed the in vitro study of intestinal biology enabling novel assays; however, its use is limited because of an inaccessible luminal compartment and challenges to data gathering in a three-dimensional hydrogel matrix. Long-lived, self-renewing 2-dimensional (2-D tissue cultured from primary colon cells has not been accomplished. Methods: The surface matrix and chemical factors that sustain 2-D mouse colonic and human rectal epithelial cell monolayers with cell repertoires comparable to that in vivo were identified. Results: The monolayers formed organoids or colonoids when placed in standard Matrigel culture. As with the colonoids, the monolayers exhibited compartmentalization of proliferative and differentiated cells, with proliferative cells located near the peripheral edges of growing monolayers and differentiated cells predominated in the central regions. Screening of 77 dietary compounds and metabolites revealed altered proliferation or differentiation of the murine colonic epithelium. When exposed to a subset of the compound library, murine organoids exhibited similar responses to that of the monolayer but with differences that were likely attributable to the inaccessible organoid lumen. The response of the human primary epithelium to a compound subset was distinct from that of both the murine primary epithelium and human tumor cells. Conclusions: This study demonstrates that a self-renewing 2-D murine and human monolayer derived from primary cells can serve as a physiologically relevant assay system for study of stem cell renewal and differentiation and for compound screening. The platform holds transformative potential for personalized and precision medicine and can be applied to emerging areas of disease modeling and microbiome studies. Keywords: Colonic Epithelial Cells, Monolayer, Organoids, Compound Screening

  9. EphA4 Regulates the Balance between Self-Renewal and Differentiation of Radial Glial Cells and Intermediate Neuronal Precursors in Cooperation with FGF Signaling.

    Directory of Open Access Journals (Sweden)

    Qingfa Chen

    Full Text Available In mouse cerebral corticogenesis, neurons are generated from radial glial cells (RGCs or from their immediate progeny, intermediate neuronal precursors (INPs. The balance between self-renewal of these neuronal precursors and specification of cell fate is critical for proper cortical development, but the signaling mechanisms that regulate this progression are poorly understood. EphA4, a member of the receptor tyrosine kinase superfamily, is expressed in RGCs during embryogenesis. To illuminate the function of EphA4 in RGC cell fate determination during early corticogenesis, we deleted Epha4 in cortical cells at E11.5 or E13.5. Loss of EphA4 at both stages led to precocious in vivo RGC differentiation toward neurogenesis. Cortical cells isolated at E14.5 and E15.5 from both deletion mutants showed reduced capacity for neurosphere formation with greater differentiation toward neurons. They also exhibited lower phosphorylation of ERK and FRS2α in the presence of FGF. The size of the cerebral cortex at P0 was smaller than that of controls when Epha4 was deleted at E11.5 but not when it was deleted at E13.5, although the cortical layers were formed normally in both mutants. The number of PAX6-positive RGCs decreased at later developmental stages only in the E11.5 Epha4 deletion mutant. These results suggest that EphA4, in cooperation with an FGF signal, contributes to the maintenance of RGC self-renewal and repression of RGC differentiation through the neuronal lineage. This function of EphA4 is especially critical and uncompensated in early stages of corticogenesis, and thus deletion at E11.5 reduces the size of the neonatal cortex.

  10. High temperature heat capacities and electrical conductivities of boron carbides

    International Nuclear Information System (INIS)

    Matsui, Tsuneo; Arita, Yuri; Naito, Keiji; Imai, Hisashi

    1991-01-01

    The heat capacities and the electrical conductivities of B x C(x=3, 4, 5) were measured by means of direct heating pulse calorimetry in the temperature range from 300 to 1500 K. The heat capacities of B x C increased with increasing x value. This increase in the heat capacity is probably related to the change of the lattice vibration mode originated from the reduction of the stiffness of the intericosahedral chain accompanied with a change from C-B-C to C-B-B chains. A linear relationship between the logarithm of σT (σ is the electrical conductivity and T is the absolute temperature) of B x C and the reciprocal temperature was observed, indicating the presence of small polaron hopping as the predominant conduction mechanism. The electrical conductivity of B x C also increased with increasing x value (from 4 to 5) due to an increase of the polaron hopping of holes between carbon atoms at geometrically nonequivalent sites, since these nonequivalent sites of carbon atoms were considered to increase in either B 11 C icosahedra or in icosahedral chains with increasing x. The electrical conductivity of B 3 C was higher than that of B 4 C, which is probably due to the precipitation of high-conducting carbon. The thermal conductivity and the thermodynamic quantities of B 4 C were also determined precisely from the heat capacity value. (orig.)

  11. SirT1—A Sensor for Monitoring Self-Renewal and Aging Process in Retinal Stem Cells

    Directory of Open Access Journals (Sweden)

    Chi-Hsien Peng

    2010-06-01

    Full Text Available Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1, a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H2O2 treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H2O2-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1. SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.

  12. A CREB-MPP7-AMOT Regulatory Axis Controls Muscle Stem Cell Expansion and Self-Renewal Competence

    Directory of Open Access Journals (Sweden)

    Lydia Li

    2017-10-01

    Full Text Available Summary: Skeletal muscle regeneration requires resident muscle stem cells, termed satellite cells (SCs. SCs are largely quiescent during homeostasis yet become activated upon injury to supply myonuclei and self-renewed SCs. Molecular mechanisms underlying the competence of SCs to proliferate and self-renew in response to injury remain unclear. Here, we show that CREB activity establishes proliferative potential during SC quiescence. SCs with inhibited CREB activity remain quiescent and positioned in their niche, but upon injury, they cannot enter or maintain a proliferative state for expansion and self-renewal. We demonstrate mechanistically that Mpp7 is a CREB target and its functional mediator. MPP7 loss affects the level and sub-cellular localization of AMOT and YAP1 in quiescent SCs. Furthermore, MPP7 and AMOT are required for YAP1 nuclear accumulation, and the three are individually required for a proliferative state in myoblasts. We propose that the CREB-MPP7-AMOT-YAP1 axis establishes the competence of quiescent SCs to expand and self-renew, thereby preserving stem cell function. : Satellite cells are quiescent muscle stem cells that have the ability to regenerate muscles after injury. Li and Fan reveal an MPP7-AMOT-YAP1 regulatory axis that acts downstream of CREB to instill satellite cell competence. They also show how this regulatory axis prepares satellite cells for robust muscle regeneration after injury.

  13. Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl.

    Science.gov (United States)

    Rojas-Ríos, Patricia; Chartier, Aymeric; Pierson, Stéphanie; Simonelig, Martine

    2017-11-02

    PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila , Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self-renewal by repressing Cbl mRNA translation and does so in part through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post-transcriptional regulators in key developmental decisions. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  14. A novel way to induce erythroid progenitor self renewal: cooperation of c-Kit with the erythropoietin receptor

    NARCIS (Netherlands)

    Wessely, O.; Bauer, A.; Quang, C. T.; Deiner, E. M.; von Lindern, M.; Mellitzer, G.; Steinlein, P.; Ghysdael, J.; Beug, H.

    1999-01-01

    Red blood cells are of vital importance for oxygen transport in vertebrates. Thus, their formation during development and homeostasis requires tight control of both progenitor proliferation and terminal red cell differentiation. Self renewal (i.e. long-term proliferation without differentiation) of

  15. High capacity, high speed histogramming data acquisition memory

    International Nuclear Information System (INIS)

    Epstein, A.; Boulin, C.

    1996-01-01

    A double width CAMAC DRAM store module was developed for use as a histogramming memory in fast time-resolved synchrotron radiation applications to molecular biology. High speed direct memory modify (3 MHz) is accomplished by using a discrete DRAM controller and fast page mode access. The module can be configured using standard SIMMs to sizes of up to 64M-words. The word width is 16 bit and the module can handle overflows by storing the overflow addresses in a dedicated FIFO. Simultaneous front panel DMM/DMI access and CAMAC readout of the overflow addresses is supported

  16. Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

    Science.gov (United States)

    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

    2010-01-01

    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

  17. Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

    Science.gov (United States)

    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

    2010-01-01

    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

  18. miR-544 Regulates Dairy Goat Male Germline Stem Cell Self-Renewal via Targeting PLZF.

    Science.gov (United States)

    Song, Wencong; Mu, Hailong; Wu, Jiang; Liao, Mingzhi; Zhu, Haijing; Zheng, Liming; He, Xin; Niu, Bowen; Zhai, Yuanxin; Bai, Chunling; Lei, Anmin; Li, Guangpeng; Hua, Jinlian

    2015-10-01

    The balance between the self-renewal and differentiation of male germline stem cells (mGSCs) is critical for the initiation and maintenance of mammalian spermatogenesis. The promyelocytic leukemia zinc finger (PLZF), a zinc finger protein, is a critical factor for maintaining the self-renewal of mGSCs, so, evaluation of the PLZF pathway in mGSCs may provide a deeper insight into mammalian spermatogenesis. miRNA was also an important regulating factor for the self-renewal and differentiation of mGSCs; however, there is currently no data indicating that which miRNA regulate the self-renewal and differentiation of mGSCs via PLZF. Here, we predicted the prospective miRNA targeting to PLZF using the online Bioinformatics database-Targetscan, and performed an analysis of the dual-luciferase recombinant vector, psiCHCEKTM-2-PLZF-3'UTR. miR-544 mimics (miR-544m), miR-544 inhibitors (miR-544i), Control (NC, scrambled oligonucleotides transfection), pPLZF-IRES2-EGFP or PLZF siRNA were transfected into mGSCs; the cells proliferation was evaluated by BRDU incorporation assay and flow cytometry, and the mGSC marker, GFRa1, PLZF, KIT, DAZL, and VASA expression were analyzed by RT-qPCR, immunofluorescence and Western blot. The results showed that miR-544 regulates dairy goat male germline stem cell self-renewal via targeting PLZF. Our study identifies a new regulatory pathway for PLZF and expands upon the PLZF regulatory network in mGSCs. © 2015 Wiley Periodicals, Inc.

  19. High voltage and high specific capacity dual intercalating electrode Li-ion batteries

    Science.gov (United States)

    West, William C. (Inventor); Blanco, Mario (Inventor)

    2010-01-01

    The present invention provides high capacity and high voltage Li-ion batteries that have a carbonaceous cathode and a nonaqueous electrolyte solution comprising LiF salt and an anion receptor that binds the fluoride ion. The batteries can comprise dual intercalating electrode Li ion batteries. Methods of the present invention use a cathode and electrode pair, wherein each of the electrodes reversibly intercalate ions provided by a LiF salt to make a high voltage and high specific capacity dual intercalating electrode Li-ion battery. The present methods and systems provide high-capacity batteries particularly useful in powering devices where minimizing battery mass is important.

  20. Colloidal silica films for high-capacity DNA arrays

    Science.gov (United States)

    Glazer, Marc Irving

    The human genome project has greatly expanded the amount of genetic information available to researchers, but before this vast new source of data can be fully utilized, techniques for rapid, large-scale analysis of DNA and RNA must continue to develop. DNA arrays have emerged as a powerful new technology for analyzing genomic samples in a highly parallel format. The detection sensitivity of these arrays is dependent on the quantity and density of immobilized probe molecules. We have investigated substrates with a porous, "three-dimensional" surface layer as a means of increasing the surface area available for the synthesis of oligonucleotide probes, thereby increasing the number of available probes and the amount of detectable bound target. Porous colloidal silica films were created by two techniques. In the first approach, films were deposited by spin-coating silica colloid suspensions onto flat glass substrates, with the pores being formed by the natural voids between the solid particles (typically 23nm pores, 35% porosity). In the second approach, latex particles were co-deposited with the silica and then pyrolyzed, creating films with larger pores (36 nm), higher porosity (65%), and higher surface area. For 0.3 mum films, enhancements of eight to ten-fold and 12- to 14-fold were achieved with the pure silica films and the films "templated" with polymer latex, respectively. In gene expression assays for up to 7,000 genes using complex biological samples, the high-capacity films provided enhanced signals and performed equivalently or better than planar glass on all other functional measures, confirming that colloidal silica films are a promising platform for high-capacity DNA arrays. We have also investigated the kinetics of hybridization on planar glass and high-capacity substrates. Adsorption on planar arrays is similar to ideal Langmuir-type adsorption, although with an "overshoot" at high solution concentration. Hybridization on high-capacity films is

  1. High-capacity aqueous zinc batteries using sustainable quinone electrodes

    Science.gov (United States)

    Zhao, Qing; Huang, Weiwei; Luo, Zhiqiang; Liu, Luojia; Lu, Yong; Li, Yixin; Li, Lin; Hu, Jinyan; Ma, Hua; Chen, Jun

    2018-01-01

    Quinones, which are ubiquitous in nature, can act as sustainable and green electrode materials but face dissolution in organic electrolytes, resulting in fast fading of capacity and short cycle life. We report that quinone electrodes, especially calix[4]quinone (C4Q) in rechargeable metal zinc batteries coupled with a cation-selective membrane using an aqueous electrolyte, exhibit a high capacity of 335 mA h g−1 with an energy efficiency of 93% at 20 mA g−1 and a long life of 1000 cycles with a capacity retention of 87% at 500 mA g−1. The pouch zinc batteries with a respective depth of discharge of 89% (C4Q) and 49% (zinc anode) can deliver an energy density of 220 Wh kg−1 by mass of both a C4Q cathode and a theoretical Zn anode. We also develop an electrostatic potential computing method to demonstrate that carbonyl groups are active centers of electrochemistry. Moreover, the structural evolution and dissolution behavior of active materials during discharge and charge processes are investigated by operando spectral techniques such as IR, Raman, and ultraviolet-visible spectroscopies. Our results show that batteries using quinone cathodes and metal anodes in aqueous electrolyte are reliable approaches for mass energy storage. PMID:29511734

  2. High-capacity composite adsorbents for nucleic acids.

    Science.gov (United States)

    Tiainen, Peter; Rokebul Anower, M; Larsson, Per-Olof

    2011-08-05

    Cytopore™ is a bead-shaped, macroporous and easily compressible cellulose-based anion-exchange material intended for cultivation of anchor-dependent animal cells. Reticulated vitreous carbon (RVC) is a strong, non-compressible, high voidage (97%) matrix material that can be cut to desired geometrical shapes. Cytopore and RVC were combined to cylindrical composites (25 mm × 10 mm) fitted inside chromatography columns. The composite combined the advantageous properties of both its constituents, making it suitable for column chromatography. The composite could withstand very high flow rates without compaction of the bed (>25 column volumes/min; 4000 cm h(-1)). Chromatography runs with tracers showed a low HETP value (0.3mm), suggesting that pore flow was in operation. The dynamic binding capacities (10% breakthrough) per gram of dry weight Cytopore were determined for several compounds including DNA and RNA and were found to be 240-370 mg/g. The composite was used to isolate pUC 18-type plasmids from a cleared alkaline lysate in a good yield. Confocal microscopy studies showed that plasmids were bound not only to the surface of the Cytopore material but also within the matrix walls, thus offering an explanation to the very high binding capacities observed. The concept of using a composite prepared from a mechanically weak, high-binding material and a strong scaffold material may be applied to other systems as well. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Cycloaddition in peptides for high-capacity optical storage

    DEFF Research Database (Denmark)

    Lohse, Brian; Berg, Rolf Henrik; Hvilsted, Søren

    2006-01-01

    Photodimerization of chromophores attached to a short peptide chain is investigated for high-capacity optical digital storage with UV lasers. The length and rigidity of the peptide chain assure an optimal distance and orientation of the chromophores for effective photodimerization. Using a theory...... developed by Tomlinson, the absorption cross section for the dimerization process in a uracil-ornithine-based hexamer is determined to be 9 x 10(-20) cm(2). A large change in the transmission due to irradiation in the UV area may make it possible to realize multilevel storage in a thin film of the peptides....

  4. Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Jamie Trott

    2017-06-01

    Full Text Available Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.

  5. The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Michalowski, A.S.

    1982-01-01

    The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

  6. The death-inducer obliterator 1 (Dido1) gene regulates embryonic stem cell self-renewal.

    Science.gov (United States)

    Liu, Yinyin; Kim, Hyeung; Liang, Jiancong; Lu, Weisi; Ouyang, Bin; Liu, Dan; Songyang, Zhou

    2014-02-21

    The regulatory network of factors that center on master transcription factors such as Oct4, Nanog, and Sox2 help maintain embryonic stem (ES) cells and ensure their pluripotency. The target genes of these master transcription factors define the ES cell transcriptional landscape. In this study, we report our findings that Dido1, a target of canonical transcription factors such as Oct4, Sox2, and Nanog, plays an important role in regulating ES cell maintenance. We found that depletion of Dido1 in mouse ES cells led to differentiation, and ectopic expression of Dido1 inhibited differentiation induced by leukemia inhibitory factor withdrawal. We further demonstrated that whereas Nanog and Oct4 could occupy the Dido1 locus and promote its transcription, Dido1 could also target to the loci of pluripotency factors such as Nanog and Oct4 and positively regulate their expression. Through this feedback and feedforward loop, Dido1 is able to regulate self-renewal of mouse ES cells.

  7. Hedgehog regulates Norrie disease protein to drive neural progenitor self-renewal.

    Science.gov (United States)

    McNeill, Brian; Mazerolle, Chantal; Bassett, Erin A; Mears, Alan J; Ringuette, Randy; Lagali, Pamela; Picketts, David J; Paes, Kim; Rice, Dennis; Wallace, Valerie A

    2013-03-01

    Norrie disease (ND) is a congenital disorder characterized by retinal hypovascularization and cognitive delay. ND has been linked to mutations in 'Norrie Disease Protein' (Ndp), which encodes the secreted protein Norrin. Norrin functions as a secreted angiogenic factor, although its role in neural development has not been assessed. Here, we show that Ndp expression is initiated in retinal progenitors in response to Hedgehog (Hh) signaling, which induces Gli2 binding to the Ndp promoter. Using a combination of genetic epistasis and acute RNAi-knockdown approaches, we show that Ndp is required downstream of Hh activation to induce retinal progenitor proliferation in the retina. Strikingly, Ndp regulates the rate of cell-cycle re-entry and not cell-cycle kinetics, thereby uncoupling the self-renewal and cell-cycle progression functions of Hh. Taken together, we have uncovered a cell autonomous function for Ndp in retinal progenitor proliferation that is independent of its function in the retinal vasculature, which could explain the neural defects associated with ND.

  8. Bmi1 regulates murine intestinal stem cell proliferation and self-renewal downstream of Notch.

    Science.gov (United States)

    López-Arribillaga, Erika; Rodilla, Verónica; Pellegrinet, Luca; Guiu, Jordi; Iglesias, Mar; Roman, Angel Carlos; Gutarra, Susana; González, Susana; Muñoz-Cánoves, Pura; Fernández-Salguero, Pedro; Radtke, Freddy; Bigas, Anna; Espinosa, Lluís

    2015-01-01

    Genetic data indicate that abrogation of Notch-Rbpj or Wnt-β-catenin pathways results in the loss of the intestinal stem cells (ISCs). However, whether the effect of Notch is direct or due to the aberrant differentiation of the transit-amplifying cells into post-mitotic goblet cells is unknown. To address this issue, we have generated composite tamoxifen-inducible intestine-specific genetic mouse models and analyzed the expression of intestinal differentiation markers. Importantly, we found that activation of β-catenin partially rescues the differentiation phenotype of Rbpj deletion mutants, but not the loss of the ISC compartment. Moreover, we identified Bmi1, which is expressed in the ISC and progenitor compartments, as a gene that is co-regulated by Notch and β-catenin. Loss of Bmi1 resulted in reduced proliferation in the ISC compartment accompanied by p16(INK4a) and p19(ARF) (splice variants of Cdkn2a) accumulation, and increased differentiation to the post-mitotic goblet cell lineage that partially mimics Notch loss-of-function defects. Finally, we provide evidence that Bmi1 contributes to ISC self-renewal. © 2015. Published by The Company of Biologists Ltd.

  9. mir-300 promotes self-renewal and inhibits the differentiation of glioma stem-like cells

    KAUST Repository

    Zhang, Daming

    2014-01-28

    MicroRNAs (miRNAs) are small noncoding RNAs that have been critically implicated in several human cancers. miRNAs are thought to participate in various biological processes, including proliferation, cell cycle, apoptosis, and even the regulation of the stemness properties of cancer stem cells. In this study, we explore the potential role of miR-300 in glioma stem-like cells (GSLCs). We isolated GSLCs from glioma biopsy specimens and identified the stemness properties of the cells through neurosphere formation assays, multilineage differentiation ability analysis, and immunofluorescence analysis of glioma stem cell markers. We found that miR-300 is commonly upregulated in glioma tissues, and the expression of miR-300 was higher in GSLCs. The results of functional experiments demonstrated that miR-300 can enhance the self-renewal of GSLCs and reduce differentiation toward both astrocyte and neural fates. In addition, LZTS2 is a direct target of miR-300. In conclusion, our results demonstrate the critical role of miR-300 in GSLCs and its functions in LZTS2 inhibition and describe a new approach for the molecular regulation of tumor stem cells. © 2014 Springer Science+Business Media.

  10. Development of High Capacity Split Stirling Cryocooler for HTS

    Science.gov (United States)

    Yumoto, Kenta; Nakano, Kyosuke; Hiratsuka, Yoshikatsu

    Sumitomo Heavy Industries, Ltd. (SHI) developed a high-power Stirling-type pulse tube cryocooler for cooling high-temperature superconductor (HTS) devices, such as superconductor motors, superconducting magnetic energy storage (SMES), and fault current limiters. The experimental results of a prototype pulse tube cryocooler were reported in September 2013. For a U-type expander, the cooling capacity was 151 W at 70 K with a compressor input power of 4 kW. Correspondingly, the coefficient of performance (COP) was about 0.038. However, the efficiency of the cryocooler is required to be COP > 0.1 and it was found that, theoretically, it is difficult to further improve the efficiency of a pulse tube cryocooler because the workflow generated at the hot end of the pulse tube cannot be recovered. Therefore, it was decided to change the expander to a free-piston type from a pulse tube type. A prototype was developed and preliminary experiments were conducted. A cooling capacity of 120 W at 70 K with a compressor input power of 2.15 kW with corresponding COP of 0.056, was obtained. The detailed results are reported in this paper.

  11. Progress in development of high capacity magnetic HTS bearings

    International Nuclear Information System (INIS)

    Kummeth, P.; Nick, W.; Neumueller, H.-W.

    2005-01-01

    HTS magnetic bearings are inherently stable without an active feedback system. They provide low frictional losses, no wear and allow operation at high rotational speed without lubrication. So they are very promising for use in motors, generators and turbines. We designed and constructed an HTS radial bearing for use with a 400 kW HTS motor. It consists of alternating axially magnetized permanent magnet rings on the rotor and a segmented YBCO stator. Stator cooling is performed by liquid nitrogen, the temperature of the stator can be adjusted by varying the pressure in the cryogenic vessel. At 68 K maximum radial forces of more than 3.7 kN were found. These results range within the highest radial bearing capacities reported worldwide. The encouraging results lead us to develop a large heavy load HTS radial bearing. Currently a high magnetic gradient HTS bearing for a 4 MVA synchronous HTS generator is under construction

  12. How a high working memory capacity can increase proactive interference.

    Science.gov (United States)

    Steinwascher, Merle A; Meiser, Thorsten

    2016-08-01

    Previous findings suggested that a high working memory capacity (WMC) is potentially associated with a higher susceptibility to proactive interference (PI) if the latter is measured under high cognitive load. To explain such a finding, we propose to consider susceptibility to PI as a net effect of individual executive processes and the intrinsic potential for PI. With the latter, we refer to the amount of information that is activated at a given time and that has the potential to exert PI subsequently. In two studies deploying generalized linear mixed models, susceptibility to PI was modeled as the decline of performance over trials of a complex span task. The results revealed that a higher WMC was associated with a higher susceptibility to PI. Moreover, the number of stimuli recalled in one trial as a proxy variable for the intrinsic potential for PI negatively affected memory performance in the subsequent trial. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Roles of Retinoids and Retinoic Acid Receptors in the Regulation of Hematopoietic Stem Cell Self-Renewal and Differentiation

    Directory of Open Access Journals (Sweden)

    Louise E. Purton

    2007-01-01

    Full Text Available Multipotent hematopoietic stem cells (HSCs sustain blood cell production throughout an individual's lifespan through complex processes ultimately leading to fates of self-renewal, differentiation or cell death decisions. A fine balance between these decisions in vivo allows for the size of the HSC pool to be maintained. While many key factors involved in regulating HSC/progenitor cell differentiation and cell death are known, the critical regulators of HSC self-renewal are largely unknown. In recent years, however, a number of studies describing methods of increasing or decreasing the numbers of HSCs in a given population have emerged. Of major interest here are the emerging roles of retinoids in the regulation of HSCs.

  14. The Role of Controlled Surface Topography and Chemistry on Mouse Embryonic Stem Cell Attachment, Growth and Self-Renewal.

    Science.gov (United States)

    Macgregor, Melanie; Williams, Rachel; Downes, Joni; Bachhuka, Akash; Vasilev, Krasimir

    2017-09-14

    The success of stem cell therapies relies heavily on our ability to control their fate in vitro during expansion to ensure an appropriate supply. The biophysical properties of the cell culture environment have been recognised as a potent stimuli influencing cellular behaviour. In this work we used advanced plasma-based techniques to generate model culture substrates with controlled nanotopographical features of 16 nm, 38 nm and 68 nm in magnitude, and three differently tailored surface chemical functionalities. The effect of these two surface properties on the adhesion, spreading, and self-renewal of mouse embryonic stem cells (mESCs) were assessed. The results demonstrated that physical and chemical cues influenced the behaviour of these stem cells in in vitro culture in different ways. The size of the nanotopographical features impacted on the cell adhesion, spreading and proliferation, while the chemistry influenced the cell self-renewal and differentiation.

  15. Capacity Decline and Characteristics Changes of Lithium-ion Cells with Large Capacity during Trickle Charge at High Temperature

    Science.gov (United States)

    Matsushima, Toshio

    Large-scale 40-Ah Li-ion cells have been developed for use in industrial applications. To contribute to techniques for ascertaining the state of these cells and detecting deterioration during actual use, we produce a cell whose capacity is reduced by trickle charging at high temperature, and we determine the relationship between the cell's properties such as its capacity and charging/discharging characteristics when the capacity is reduced. When the capacity of a Li-ion cell is reduced, the discharge voltage also decreases. We show that the residual capacity is well correlated to the discharge voltage and to the duration of continuous discharge before reaching a fixed end-voltage. We also show that the constant-current constant-voltage charging characteristics are maintained even when the capacity is degraded, and that the constant-current charging time and discharge voltage are closely related to the residual capacity. We confirm that the reaction coefficient of the capacity degradation formula can be calculated from the capacity change characteristics at multiple temperatures, and that an 8°C change in temperature causes the lifetime to decrease by half.

  16. Mesoporous Silicon-Based Anodes for High Capacity, High Performance Li-ion Batteries, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A new high capacity anode composite based on mesoporous silicon is proposed. By virtue of a structure that resembles a pseudo one-dimensional phase, the active anode...

  17. High-Capacity Spacesuit Evaporator Absorber Radiator (SEAR)

    Science.gov (United States)

    Izenson, Michael G.; Chen, Weibo; Phillips, Scott; Chepko, Ariane; Bue, Grant; Quinn, Gregory

    2015-01-01

    Future human space exploration missions will require advanced life support technology that can operate across a wide range of applications and environments. Thermal control systems for space suits and spacecraft will need to meet critical requirements for water conservation and multifunctional operation. This paper describes a Space Evaporator Absorber Radiator (SEAR) that has been designed to meet performance requirements for future life support systems. A SEAR system comprises a lithium chloride absorber radiator (LCAR) for heat rejection coupled with a space water membrane evaporator (SWME) for heat acquisition. SEAR systems provide heat pumping to minimize radiator size, thermal storage to accommodate variable environmental conditions, and water absorption to minimize use of expendables. We have built and tested a flight-like, high-capacity LCAR, demonstrated its performance in thermal vacuum tests, and explored the feasibility of an ISS demonstration test of a SEAR system. The new LCAR design provides the same cooling capability as prior LCAR prototypes while enabling over 30% more heat absorbing capacity. Studies show that it should be feasible to demonstrate SEAR operation in flight by coupling with an existing EMU on the space station.

  18. TMPRSS2- driven ERG expression in vivo increases self-renewal and maintains expression in a castration resistant subpopulation.

    Directory of Open Access Journals (Sweden)

    Orla M Casey

    Full Text Available Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the promoter region of TMPRSS2 with the coding region of the transcription factor, ERG. A recombinant bacterial artificial chromosome including an extended TMPRSS2 promoter driving genomic ERG was constructed and used for transgenesis in mice. TMPRSS2-ERG expression was evaluated in tissue sections and FACS-fractionated prostate cell populations. In addition to the anticipated expression in luminal cells, TMPRSS2-ERG was similarly expressed in the Sca-1(hi/EpCAM(+ basal/progenitor fraction, where expanded numbers of clonogenic self-renewing progenitors were found, as assayed by in vitro sphere formation. These clonogenic cells increased intrinsic self renewal in subsequent generations. In addition, ERG dependent self-renewal and invasion in vitro was demonstrated in prostate cell lines derived from the model. Clinical studies have suggested that the TMPRSS2-ERG translocation occurs early in prostate cancer development. In the model described here, the presence of the TMPRSS2-ERG fusion alone was not transforming but synergized with heterozygous Pten deletion to promote PIN. Taken together, these data suggest that one function of TMPRSS2-ERG is the expansion of self-renewing cells, which may serve as targets for subsequent mutations. Primary prostate epithelial cells demonstrated increased post transcriptional turnover of ERG compared to the TMPRSS2-ERG positive VCaP cell line, originally isolated from a prostate cancer metastasis. Finally, we determined that TMPRSS2-ERG expression occurred in both castration-sensitive and resistant prostate epithelial subpopulations, suggesting the existence of androgen-independent mechanisms of TMPRSS2 expression in prostate epithelium.

  19. Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self-Renewal.

    Science.gov (United States)

    Villa-Diaz, Luis G; Kim, Jin Koo; Laperle, Alex; Palecek, Sean P; Krebsbach, Paul H

    2016-07-01

    Self-renewal of human embryonic stem cells and human induced pluripotent stem cells (hiPSCs)-known as pluripotent stem cells (PSC)-is influenced by culture conditions, including the substrate on which they are grown. However, details of the molecular mechanisms interconnecting the substrate and self-renewal of these cells remain unclear. We describe a signaling pathway in hPSCs linking self-renewal and expression of pluripotency transcription factors to integrin α6β1 and inactivation of focal adhesion kinase (FAK). Disruption of this pathway results in hPSC differentiation. In hPSCs, α6β1 is the dominant integrin and FAK is not phosphorylated at Y397, and thus, it is inactive. During differentiation, integrin α6 levels diminish and Y397 FAK is phosphorylated and activated. During reprogramming of fibroblasts into iPSCs, integrin α6 is upregulated and FAK is inactivated. Knockdown of integrin α6 and activation of β1 integrin lead to FAK phosphorylation and reduction of Nanog, Oct4, and Sox2, suggesting that integrin α6 functions in inactivation of integrin β1 and FAK signaling and prevention of hPSC differentiation. The N-terminal domain of FAK, where Y397 is localized, is in the nuclei of hPSCs interacting with Oct4 and Sox2, and this immunolocalization is regulated by Oct4. hPSCs remodel the extracellular microenvironment and deposit laminin α5, the primary ligand of integrin α6β1. Knockdown of laminin α5 resulted in reduction of integrin α6 expression, phosphorylation of FAK and decreased Oct4. In conclusion, hPSCs promote the expression of integrin α6β1, and nuclear localization and inactivation of FAK to supports stem cell self-renewal. Stem Cells 2016;34:1753-1764. © 2016 AlphaMed Press.

  20. The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche.

    Science.gov (United States)

    Issigonis, Melanie; Matunis, Erika

    2012-08-15

    Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAK-STAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. When High-Capacity Readers Slow Down and Low-Capacity Readers Speed Up: Working Memory and Locality Effects.

    Science.gov (United States)

    Nicenboim, Bruno; Logačev, Pavel; Gattei, Carolina; Vasishth, Shravan

    2016-01-01

    We examined the effects of argument-head distance in SVO and SOV languages (Spanish and German), while taking into account readers' working memory capacity and controlling for expectation (Levy, 2008) and other factors. We predicted only locality effects, that is, a slowdown produced by increased dependency distance (Gibson, 2000; Lewis and Vasishth, 2005). Furthermore, we expected stronger locality effects for readers with low working memory capacity. Contrary to our predictions, low-capacity readers showed faster reading with increased distance, while high-capacity readers showed locality effects. We suggest that while the locality effects are compatible with memory-based explanations, the speedup of low-capacity readers can be explained by an increased probability of retrieval failure. We present a computational model based on ACT-R built under the previous assumptions, which is able to give a qualitative account for the present data and can be tested in future research. Our results suggest that in some cases, interpreting longer RTs as indexing increased processing difficulty and shorter RTs as facilitation may be too simplistic: The same increase in processing difficulty may lead to slowdowns in high-capacity readers and speedups in low-capacity ones. Ignoring individual level capacity differences when investigating locality effects may lead to misleading conclusions.

  2. When high-capacity readers slow down and low-capacity readers speed up: Working memory and locality effects

    Directory of Open Access Journals (Sweden)

    Bruno eNicenboim

    2016-03-01

    Full Text Available We examined the effects of argument-head distance in SVO and SOV languages (Spanish and German, while taking into account readers’ working memory capacity and controlling for expectation (Levy, 2008 and other factors. We predicted only locality effects, that is, a slow-down produced by increased dependency distance (Gibson, 2000; Lewis & Vasishth, 2005. Furthermore, we expected stronger locality effects for readers with low working memory capacity. Contrary to our predictions, low-capacity readers showed faster reading with increased distance, while high-capacity readers showed locality effects. We suggest that while the locality effects are compatible with memory-based explanations, the speedup of low-capacity readers can be explained by an increased probability of retrieval failure. We present a computational model based on ACT-R built under the previous assumptions, which is able to give a qualitative account for the present data and can be tested in future research. Our results suggest that in some cases, interpreting longer RTs as indexing increased processing difficulty and shorter RTs as facilitation may be too simplistic: The same increase in processing difficulty may lead to slowdowns in high-capacity readers and speedups in low-capacity ones. Ignoring individual level capacity differences when investigating locality effects may lead to misleading conclusions.

  3. Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self-renewal and pluripotency.

    Science.gov (United States)

    Gong, Jiaqi; Gu, Haifeng; Zhao, Lin; Wang, Liang; Liu, Pinglei; Wang, Fuping; Xu, Haoyu; Zhao, Tongbiao

    2018-01-18

    Autophagy is a catabolic process to degrade both damaged organelles and aggregated proteins in somatic cells. We have recently identified that autophagy is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and thus contribute to stemness regulation. However, the regulatory and functional mechanisms of autophagy in ESC are still largely unknown. Here we have shown that activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency. Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised self-renewal and pluripotency. These defects can be rescued by reacquisition of wild-type ULK1 and ULK1(S757A) mutant, but not ULK1(S317A, S555A and S777A) and kinase dead ULK1(K46I) mutant. These data indicate that phosphorylation of ULK1 by AMPK, but not mTOR, is essential for stemness regulation in ESC. The findings highlight a critical role for AMPK-dependent phosphorylation of ULK1 pathway to maintain ESC self-renewal and pluripotency.

  4. Yap1 is dispensable for self-renewal but required for proper differentiation of mouse embryonic stem (ES) cells.

    Science.gov (United States)

    Chung, HaeWon; Lee, Bum-Kyu; Uprety, Nadima; Shen, Wenwen; Lee, Jiwoon; Kim, Jonghwan

    2016-04-01

    Yap1 is a transcriptional co-activator of the Hippo pathway. The importance of Yap1 in early cell fate decision during embryogenesis has been well established, though its role in embryonic stem (ES) cells remains elusive. Here, we report that Yap1 plays crucial roles in normal differentiation rather than self-renewal of ES cells. Yap1-depleted ES cells maintain undifferentiated state with a typical colony morphology as well as robust alkaline phosphatase activity. These cells also retain comparable levels of the core pluripotent factors, such as Pou5f1 and Sox2, to the levels in wild-type ES cells without significant alteration of lineage-specific marker genes. Conversely, overexpression of Yap1 in ES cells promotes nuclear translocation of Yap1, resulting in disruption of self-renewal and triggering differentiation by up-regulating lineage-specific genes. Moreover, Yap1-deficient ES cells show impaired induction of lineage markers during differentiation. Collectively, our data demonstrate that Yap1 is a required factor for proper differentiation of mouse ES cells, while remaining dispensable for self-renewal. © 2016 The Authors.

  5. BMP Sustains Embryonic Stem Cell Self-Renewal through Distinct Functions of Different Krüppel-like Factors.

    Science.gov (United States)

    Morikawa, Masato; Koinuma, Daizo; Mizutani, Anna; Kawasaki, Natsumi; Holmborn, Katarina; Sundqvist, Anders; Tsutsumi, Shuichi; Watabe, Tetsuro; Aburatani, Hiroyuki; Heldin, Carl-Henrik; Miyazono, Kohei

    2016-01-12

    Bone morphogenetic protein (BMP) signaling exerts paradoxical roles in pluripotent stem cells (PSCs); it sustains self-renewal of mouse embryonic stem cells (ESCs), while it induces differentiation in other PSCs, including human ESCs. Here, we revisit the roles of BMP-4 using mouse ESCs (mESCs) in naive and primed states. SMAD1 and SMAD5, which transduce BMP signals, recognize enhancer regions together with KLF4 and KLF5 in naive mESCs. KLF4 physically interacts with SMAD1 and suppresses its activity. Consistently, a subpopulation of cells with active BMP-SMAD can be ablated without disturbing the naive state of the culture. Moreover, Smad1/5 double-knockout mESCs stay in the naive state, indicating that the BMP-SMAD pathway is dispensable for it. In contrast, the MEK5-ERK5 pathway mediates BMP-4-induced self-renewal of mESCs by inducing Klf2, a critical factor for the ground state pluripotency. Our study illustrates that BMP exerts its self-renewing effect through distinct functions of different Krüppel-like factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Lipopolysaccharide inhibits the self-renewal of spermatogonial stem cells in vitro via downregulation of GDNF expression in Sertoli cells.

    Science.gov (United States)

    Zhang, Xiaoli; Shi, Kun; Li, Yi; Zhang, Haiyu; Hao, Jing

    2014-06-01

    Lipopolysaccharide (LPS) can reduce sperm count and sperm quality. The molecular mechanisms underlying this process are not fully understood. In this report, we investigated the effects of LPS-treated Sertoli cells on self-renewal and differentiation of spermatogoinial stem cells (SSCs). Sertoli cell cultures were established and incubated with LPS (10μg/ml) for 1, 2 or 3 days, respectively. The culture media were collected and used as conditioned media (CM) to culture SSCs. The expression of glial cell-derived neurotrophic factor (GDNF), stem cell factor (SCF) and bone morphogenetic protein 4 (BMP4) in Sertoli cells treated with LPS was analyzed by RT-PCR and Western blotting. The results showed that the expression of SSC differentiation markers, c-kit and Sohlh2, was increased, while the expression of SSC self-renewal markers, plzf, oct4, and PCNA, was repressed when cultured in CM from LPS-treated Sertoli cells. GDNF levels in Sertoli cells and CM reduced dramatically after LPS treatments, while SCF and BMP4 levels did not show any significant changes. Moreover, correlated with the GDNF levels in CM, GDNF target genes, Bcl6b and Etv5, were reduced markedly in SSCs. Our results suggest that LPS inhibits the expression of GDNF in Sertoli cells, and might prevent the SSC self-renewal via down-regulation of GDNF target genes. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells

    Science.gov (United States)

    Butler, Jason M.; Nolan, Daniel J.; L.Vertes, Eva; Varnum-Finney, Barbara; Kobayashi, Hideki; Hooper, Andrea T.; Seandel, Marco; Shido, Koji; White, Ian A.; Kobayashi, Mariko; Witte, Larry; May, Chad; Shawber, Carrie; Kimura, Yuki; Kitajewski, Jan; Rosenwaks, Zev; Bernstein, Irwin D.; Rafii, Shahin

    2010-01-01

    Bone marrow endothelial cells (ECs) are essential for reconstitution of hematopoiesis, but their role in self-renewal of long term-hematopoietic stem cells (LT-HSCs) is unknown. We have developed angiogenic models to demonstrate that EC-derived angiocrine growth factors support in vitro self-renewal and in vivo repopulation of authentic LT-HSCs. In serum/cytokine-free co-cultures, ECs through direct cellular contact, stimulated incremental expansion of repopulating CD34−Flt3−cKit+Lineage−Sca1+ LT-HSCs, which retained their self-renewal ability, as determined by single cell and serial transplantation assays. Angiocrine expression of Notch-ligands by ECs promoted proliferation and prevented exhaustion of LT-HSCs derived from wild-type, but not Notch1/Notch2 deficient mice. In transgenic notch-reporter (TNR.Gfp) mice, regenerating TNR.Gfp+ LT-HSCs were detected in cellular contact with sinusoidal ECs and interfering with angiocrine, but not perfusion function, of SECs impaired repopulation of TNR.Gfp+ LT-HSCs. ECs establish an instructive vascular niche for clinical scale expansion of LT-HSCs and a cellular platform to identify stem cell-active trophogens. PMID:20207228

  8. GROα regulates human embryonic stem cell self-renewal or adoption of a neuronal fate

    Science.gov (United States)

    Krtolica, Ana; Larocque, Nick; Genbacev, Olga; Ilic, Dusko; Coppe, Jean-Philippe; Patil, Christopher K.; Zdravkovic, Tamara; McMaster, Michael; Campisi, Judith; Fisher, Susan J.

    2012-01-01

    Previously we reported that feeders formed from human placental fibroblasts (hPFs) support derivation and long-term self-renewal of human embryonic stem cells (hESCs) under serum-free conditions. Here, we show, using antibody array and ELISA platforms, that hPFs secrete ~6-fold higher amounts of the CXC-type chemokine, GROα, than IMR 90, a human lung fibroblast line, which does not support hESC growth. Furthermore, immunocytochemistry and immunoblot approaches revealed that hESCs express CXCR, a GROα receptor. We used this information to develop defined culture medium for feeder-free propagation of hESCs in an undifferentiated state. Cells passaged as small aggregates and maintained in the GROα-containing medium had a normal karyotype, expressed pluripotency markers, and exhibited apical–basal polarity, i.e., had the defining features of pluripotent hESCs. They also differentiated into the three primary (embryonic) germ layers and formed teratomas in immunocompromised mice. hESCs cultured as single cells in the GROα-containing medium also had a normal karyotype, but they downregulated markers of pluripotency, lost apical–basal polarity, and expressed markers that are indicative of the early stages of neuronal differentiation—βIII tubulin, vimentin, radial glial protein, and nestin. These data support our hypothesis that establishing and maintaining cell polarity is essential for the long-term propagation of hESCs in an undifferentiated state and that disruption of cell–cell contacts can trigger adoption of a neuronal fate. PMID:21396766

  9. Enhancement of human neural stem cell self-renewal in 3D hypoxic culture.

    Science.gov (United States)

    Ghourichaee, Sasan Sharee; Powell, Elizabeth M; Leach, Jennie B

    2017-05-01

    The pathology of neurological disorders is associated with the loss of neuronal and glial cells that results in functional impairments. Human neural stem cells (hNSCs), due to their self-renewing and multipotent characteristics, possess enormous tissue-specific regenerative potential. However, the efficacy of clinical applications is restricted due to the lack of standardized in vitro cell production methods with the capability of generating hNSC populations with well-defined cellular compositions. At any point, a population of hNSCs may include undifferentiated stem cells, intermediate and terminally differentiated progenies, and dead cells. Due to the plasticity of hNSCs, environmental cues play crucial roles in determining the cellular composition of hNSC cultures over time. Here, we investigated the independent and synergistic effect of three important environmental factors (i.e., culture dimensionality, oxygen concentration, and growth factors) on the survival, renewal potential, and differentiation of hNSCs. Our experimental design included two dimensional (2D) versus three dimensional (3D) cultures and normoxic (21% O 2 ) versus hypoxic (3% O 2 ) conditions in the presence and absence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Additionally, we discuss the feasibility of mathematical models that predict hNSC growth and differentiation under these culture conditions by adopting a negative feedback regulatory term. Our results indicate that the synergistic effect of culture dimensionality and hypoxic oxygen concentration in the presence of growth factors enhances the proliferation of viable, undifferentiated hNSCs. Moreover, the same synergistic effect in the absence of growth factors promotes the differentiation of hNSCs. Biotechnol. Bioeng. 2017;114: 1096-1106. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell.

    Directory of Open Access Journals (Sweden)

    Luciano Conti

    2005-09-01

    Full Text Available Pluripotent mouse embryonic stem (ES cells multiply in simple monoculture by symmetrical divisions. In vivo, however, stem cells are generally thought to depend on specialised cellular microenvironments and to undergo predominantly asymmetric divisions. Ex vivo expansion of pure populations of tissue stem cells has proven elusive. Neural progenitor cells are propagated in combination with differentiating progeny in floating clusters called neurospheres. The proportion of stem cells in neurospheres is low, however, and they cannot be directly observed or interrogated. Here we demonstrate that the complex neurosphere environment is dispensable for stem cell maintenance, and that the combination of fibroblast growth factor 2 (FGF-2 and epidermal growth factor (EGF is sufficient for derivation and continuous expansion by symmetrical division of pure cultures of neural stem (NS cells. NS cells were derived first from mouse ES cells. Neural lineage induction was followed by growth factor addition in basal culture media. In the presence of only EGF and FGF-2, resulting NS cells proliferate continuously, are diploid, and clonogenic. After prolonged expansion, they remain able to differentiate efficiently into neurons and astrocytes in vitro and upon transplantation into the adult brain. Colonies generated from single NS cells all produce neurons upon growth factor withdrawal. NS cells uniformly express morphological, cell biological, and molecular features of radial glia, developmental precursors of neurons and glia. Consistent with this profile, adherent NS cell lines can readily be established from foetal mouse brain. Similar NS cells can be generated from human ES cells and human foetal brain. The extrinsic factors EGF plus FGF-2 are sufficient to sustain pure symmetrical self-renewing divisions of NS cells. The resultant cultures constitute the first known example of tissue-specific stem cells that can be propagated without accompanying

  11. High oil prices: A non-OPEC capacity game

    International Nuclear Information System (INIS)

    Osmundsen, Petter; Asche, Frank; Misund, Baard; Mohn, Klaus

    2005-08-01

    The current high oil price is partly due to low investments in the oil industry the last decade. According to economic theory, exploration and development of new oil and gas fields should respond positively to increasing petroleum prices. But since the late 1990s, financial analysts have focused strongly on short-term accounting return measures, like RoACE, for benchmarking and valuation of international oil and gas companies. Consequently, the demand for strict capital discipline among oil and gas companies may have reduced their willingness to invest for future reserves and production growth. Thus, we have experienced an unusual combination of high oil prices and low investment levels in exploration and development. In many ways, the oil companies' focus on RoACE, at the expense of reserve replacement, resembles an implicit co-ordination on low capacity among non-OPEC petroleum producers. This is a partial explanation of the current high oil prices. By examining actual parameters used by the financial markets in pricing of oil companies, we address the issue of whether the low investment outcome could represent a long-term equilibrium. This is hardly likely, as oil companies are made aware that stronger emphasis is put on reserve replacement. (Author)

  12. Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity

    Science.gov (United States)

    Karvinen, Sira M.; Silvennoinen, Mika; Ma, Hongqiang; Törmäkangas, Timo; Rantalainen, Timo; Rinnankoski-Tuikka, Rita; Lensu, Sanna; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

    2016-01-01

    The production of heat, i.e., thermogenesis, is a significant component of the metabolic rate, which in turn affects weight gain and health. Thermogenesis is linked to physical activity (PA) level. However, it is not known whether intrinsic exercise capacity, aging, and long-term voluntary running affect core body temperature. Here we use rat models selectively bred to differ in maximal treadmill endurance running capacity (Low capacity runners, LCR and High capacity Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging, and metabolic disease risk to study the connection between PA and body temperature. Ten high capacity runner (HCR) and ten low capacity runner (LCR) female rats were studied between 9 and 21 months of age. Rectal body temperature of HCR and LCR rats was measured before and after 1-year voluntary running/control intervention to explore the effects of aging and PA. Also, we determined whether injected glucose and spontaneous activity affect the body temperature differently between LCR and HCR rats at 9 vs. 21 months of age. HCRs had on average 1.3°C higher body temperature than LCRs (p temperature level of HCRs to similar levels with LCRs. The opportunity to run voluntarily had a significant impact on the body temperature of HCRs (p temperature at a similar level as when at younger age. Compared to LCRs, HCRs were spontaneously more active, had higher relative gastrocnemius muscle mass and higher UCP2, PGC-1α, cyt c, and OXPHOS levels in the skeletal muscle (p temperature of LCRs. However, glucose injection resulted in a lowering of the body temperature of LCRs (p temperature compared to rats born with low exercise capacity and disease risk. Voluntary running allowed HCRs to maintain high body temperature during aging, which suggests that high PA level was crucial in maintaining the high body temperature of HCRs. PMID:27504097

  13. Glial cell line-derived neurotrophic factor and endothelial cells promote self-renewal of rabbit germ cells with spermatogonial stem cell properties.

    Science.gov (United States)

    Kubota, Hiroshi; Wu, Xin; Goodyear, Shaun M; Avarbock, Mary R; Brinster, Ralph L

    2011-08-01

    Previous studies suggest that exogenous factors crucial for spermatogonial stem cell (SSC) self-renewal are conserved among several mammalian species. Since glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are critical for rodent SSC self-renewal, we hypothesized that they might promote self-renewal of nonrodent SSCs. Therefore, we cultured testicular germ cells from prepubertal rabbits in the presence of GDNF and FGF2 and found they proliferated indefinitely as cellular clumps that displayed characteristics previously identified for rodent SSCs. The rabbit germ cells could not be maintained on mouse embryonic fibroblast (STO) feeders that support rodent SSC self-renewal in vitro but were rather supported on mouse yolk sac-derived endothelial cell (C166) feeder layers. Proliferation of rabbit germ cells was dependent on GDNF. Of critical importance was that clump-forming rabbit germ cells colonized seminiferous tubules of immunodeficient mice, proliferated for at least 6 mo, while retaining an SSC phenotype in the testes of recipient mice, indicating that they were rabbit SSCs. This study demonstrates that GDNF is a mitogenic factor promoting self-renewal that is conserved between rodent and rabbit SSCs; with an evolutionary separation of ∼ 60 million years. These findings provide a foundation to study the mechanisms governing SSC self-renewal in nonrodent species.

  14. The C. elegans engrailed homolog ceh-16 regulates the self-renewal expansion division of stem cell-like seam cells.

    Science.gov (United States)

    Huang, Xinxin; Tian, E; Xu, Yanhua; Zhang, Hong

    2009-09-15

    Stem cells undergo symmetric and asymmetric division to maintain the dynamic equilibrium of the stem cell pool and also to generate a variety of differentiated cells. The homeostatic mechanism controlling the choice between self-renewal and differentiation of stem cells is poorly understood. We show here that ceh-16, encoding the C. elegans ortholog of the transcription factor Engrailed, controls symmetric and asymmetric division of stem cell-like seam cells. Loss of function of ceh-16 causes certain seam cells, which normally undergo symmetric self-renewal expansion division with both daughters adopting the seam cell fate, to divide asymmetrically with only one daughter retaining the seam cell fate. The human engrailed homolog En2 functionally substitutes the role of ceh-16 in promoting self-renewal expansion division of seam cells. Loss of function of apr-1, encoding the C. elegans homolog of the Wnt signaling component APC, results in transformation of self-renewal maintenance seam cell division to self-renewal expansion division, leading to seam cell hyperplasia. The apr-1 mutation suppresses the seam cell division defect in ceh-16 mutants. Our study reveals that ceh-16 interacts with the Wnt signaling pathway to control the choice between self-renewal expansion and maintenance division and also demonstrates an evolutionarily conserved function of engrailed in promoting cell proliferation.

  15. Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors.

    Science.gov (United States)

    Xie, Ting

    2013-01-01

    In the Drosophila ovary, germline stem cells (GSCs) physically interact with their niche composed of terminal filament cells, cap cells, and possibly GSC-contacting escort cells (ECs). A GSC divides to generate a self-renewing stem cell that remains in the niche and a differentiating daughter that moves away from the niche. The GSC niche provides a bone morphogenetic protein (BMP) signal that maintains GSC self-renewal by preventing stem cell differentiation via repression of the differentiation-promoting gene bag of marbles (bam). In addition, it expresses E-cadherin, which mediates cell adhesion for anchoring GSCs in the niche, enabling continuous self-renewal. GSCs themselves also express different classes of intrinsic factors, including signal transducers, transcription factors, chromatin remodeling factors, translation regulators, and miRNAs, which control self-renewal by strengthening interactions with the niche and repressing various differentiation pathways. Differentiated GSC daughters, known as cystoblasts (CBs), also express distinct classes of intrinsic factors to inhibit self-renewal and promote germ cell differentiation. Surprisingly, GSC progeny are also dependent on their surrounding ECs for proper differentiation at least partly by preventing BMP from diffusing to the differentiated germ cell zone and by repressing ectopic BMP expression. Therefore, both GSC self-renewal and CB differentiation are controlled by collaborative actions of extrinsic signals and intrinsic factors. Copyright © 2012 Wiley Periodicals, Inc.

  16. Promyelocytic leukaemia zinc finger maintains self-renewal of male germline stem cells (mGSCs) and its expression pattern in dairy goat testis.

    Science.gov (United States)

    Song, W; Zhu, H; Li, M; Li, N; Wu, J; Mu, H; Yao, X; Han, W; Liu, W; Hua, J

    2013-08-01

    Previous studies have shown that promyelocytic leukaemia zinc finger (PLZF) is a spermatogonia-specific transcription factor in the testis, required to regulate self-renewal and maintenance of the spermatogonia stem cell. Up to now, expression and function of PLZF in the goat testis has not been known. The objectives of this study were to investigate PLZF expression pattern in the dairy goat and its effect on male goat germline stem cell (mGSC) self-renewal and differentiation. Testis development and expression patterns of PLZF in the dairy goat were analysed by haematoxylin and eosin staining, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, effects of PLZF overexpression on mGSC self-renewal and differentiation were evaluated by quantitative RT-PCR (QRT-PCR), immunofluorescence and BrdU incorporation assay. Promyelocytic leukaemia zinc finger was essential for dairy goat testis development and expression of several proliferation and pluripotency-associated proteins including OCT4, C-MYC were upregulated by PLZF overexpression. The study demonstrated that PLZF played a key role in maintaining self-renewal of mGSCs and its overexpression enhanced expression of proliferation-associated genes. Promyelocytic leukaemia zinc finger could function in the dairy goat as well as in other species in maintaining self-renewal of germline stem cells and this study provides a model to study the mechanism on self-renewal and differentiation of mGSCs in livestock. © 2013 John Wiley & Sons Ltd.

  17. PGE2 maintains self-renewal of human adult stem cells via EP2-mediated autocrine signaling and its production is regulated by cell-to-cell contact.

    Science.gov (United States)

    Lee, Byung-Chul; Kim, Hyung-Sik; Shin, Tae-Hoon; Kang, Insung; Lee, Jin Young; Kim, Jae-Jun; Kang, Hyun Kyoung; Seo, Yoojin; Lee, Seunghee; Yu, Kyung-Rok; Choi, Soon Won; Kang, Kyung-Sun

    2016-05-27

    Mesenchymal stem cells (MSCs) possess unique immunomodulatory abilities. Many studies have elucidated the clinical efficacy and underlying mechanisms of MSCs in immune disorders. Although immunoregulatory factors, such as Prostaglandin E2 (PGE2), and their mechanisms of action on immune cells have been revealed, their effects on MSCs and regulation of their production by the culture environment are less clear. Therefore, we investigated the autocrine effect of PGE2 on human adult stem cells from cord blood or adipose tissue, and the regulation of its production by cell-to-cell contact, followed by the determination of its immunomodulatory properties. MSCs were treated with specific inhibitors to suppress PGE2 secretion, and proliferation was assessed. PGE2 exerted an autocrine regulatory function in MSCs by triggering E-Prostanoid (EP) 2 receptor. Inhibiting PGE2 production led to growth arrest, whereas addition of MSC-derived PGE2 restored proliferation. The level of PGE2 production from an equivalent number of MSCs was down-regulated via gap junctional intercellular communication. This cell contact-mediated decrease in PGE2 secretion down-regulated the suppressive effect of MSCs on immune cells. In conclusion, PGE2 produced by MSCs contributes to maintenance of self-renewal capacity through EP2 in an autocrine manner, and PGE2 secretion is down-regulated by cell-to-cell contact, attenuating its immunomodulatory potency.

  18. Surface and bulk modified high capacity layered oxide cathodes with low irreversible capacity loss

    Science.gov (United States)

    Manthiram, Arumugam (Inventor); Wu, Yan (Inventor)

    2010-01-01

    The present invention includes compositions, surface and bulk modifications, and methods of making of (1-x)Li[Li.sub.1/3Mn.sub.2/3]O.sub.2.xLi[Mn.sub.0.5-yNi.sub.0.5-yCo.sub.2- y]O.sub.2 cathode materials having an O3 crystal structure with a x value between 0 and 1 and y value between 0 and 0.5, reducing the irreversible capacity loss in the first cycle by surface modification with oxides and bulk modification with cationic and anionic substitutions, and increasing the reversible capacity to close to the theoretical value of insertion/extraction of one lithium per transition metal ion (250-300 mAh/g).

  19. Space qualification of high capacity grooved heat pipes

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, M; Mullender, B; Druart, J [SABCA, Societe Anomyme Belgel de Construction Aeronautique (Belgium); Supper, W; Beddows, A [ESTEC-The (Netherlands)

    1997-12-31

    Based on the thermal requirements of the future telecommunication satellites, the development of a High Capacity Grooved Heat Pipe (HPG), was contracted by ESA to SABCA leading to an aluminium extruded heat pipe (outer diameter of 25 mm) based on a multi re-entrant grooves design. After an intensive acceptance test campaign whose results showed a good confidence in the design and the fulfillment of the required specifications of heat transport and on tilt capability (experimental maximum heat transport capability of 1500 Watt metres for a vapour temperature of 20 deg C), similar heat pipes have been developed with various outer diameters (11 mm, 15 mm and 20 mm) and with various shapes (circular outer shapes, integrated saddles). Several of these heat pipes were tested during two parabolic flight campaigns, by varying the heat loads during the micro-gravity periods. This HGP heat pipe family is now being submitted to a space qualification program according to ESA standards (ESA PSS-49), both in straight and bent configuration. Within this qualification, the heat pipes are submitted to an extended test campaign including environmental (random/sinus vibration, constant acceleration) and thermal tests (thermal performance, thermal cycle, thermal soak, ageing). (authors) 9 refs.

  20. Space qualification of high capacity grooved heat pipes

    Energy Technology Data Exchange (ETDEWEB)

    Dubois, M.; Mullender, B.; Druart, J. [SABCA, Societe Anomyme Belgel de Construction Aeronautique (Belgium); Supper, W.; Beddows, A. [ESTEC-The (Netherlands)

    1996-12-31

    Based on the thermal requirements of the future telecommunication satellites, the development of a High Capacity Grooved Heat Pipe (HPG), was contracted by ESA to SABCA leading to an aluminium extruded heat pipe (outer diameter of 25 mm) based on a multi re-entrant grooves design. After an intensive acceptance test campaign whose results showed a good confidence in the design and the fulfillment of the required specifications of heat transport and on tilt capability (experimental maximum heat transport capability of 1500 Watt metres for a vapour temperature of 20 deg C), similar heat pipes have been developed with various outer diameters (11 mm, 15 mm and 20 mm) and with various shapes (circular outer shapes, integrated saddles). Several of these heat pipes were tested during two parabolic flight campaigns, by varying the heat loads during the micro-gravity periods. This HGP heat pipe family is now being submitted to a space qualification program according to ESA standards (ESA PSS-49), both in straight and bent configuration. Within this qualification, the heat pipes are submitted to an extended test campaign including environmental (random/sinus vibration, constant acceleration) and thermal tests (thermal performance, thermal cycle, thermal soak, ageing). (authors) 9 refs.

  1. Development of high capacity, high rate lithium ion batteries utilizing metal fiber conductive additives

    Science.gov (United States)

    Ahn, Soonho; Kim, Youngduk; Kim, Kyung Joon; Kim, Tae Hyung; Lee, Hyungkeun; Kim, Myung H.

    As lithium ion cells dominate the battery market, the performance improvement is an utmost concern among developers and researchers. Conductive additives are routinely employed to enhance electrode conductivity and capacity. Carbon particulates—graphite or carbon black powders—are conventional and popular choices as conductive fillers. However, percolation requirements of particles demand significant volumetric content of impalpable, and thereby high area conductive fillers. As might be expected, the electrode active surface area escalates unnecessarily, resulting in overall increase in reaction with electrolytes and organic solvents. The increased reactions usually manifest as an irreversible loss of anode capacity, gradual oxidation and consumption of electrolyte on the cathode—which causes capacity decline during cycling—and an increased threat to battery safety by gas evolution and exothermic solvent oxidation. In this work we have utilized high aspect ratio, flexible, micronic metal fibers as low active area and high conductivity additives. The metal fibers appear well dispersed within the electrode and to satisfy percolation requirements very efficiently at very low volumetric content compared to conventional carbon-based conductive additives. Results from 18650-type cells indicate significant enhancements in electrode capacity and high rate capability while the irreversible capacity loss is negligible.

  2. Optical signal processing for enabling high-speed, highly spectrally efficient and high capacity optical systems

    Science.gov (United States)

    Fazal, Muhammad Irfan

    The unabated demand for more capacity due to the ever-increasing internet traffic dictates that the boundaries of the state of the art maybe pushed to send more data through the network. Traditionally, this need has been satisfied by multiple wavelengths (wavelength division multiplexing), higher order modulation formats and coherent communication (either individually or combined together). WDM has the ability to reduce cost by using multiple channels within the same physical fiber, and with EDFA amplifiers, the need for O-E-O regenerators is eliminated. Moreover the availability of multiple colors allows for wavelength-based routing and network planning. Higher order modulation formats increases the capacity of the link by their ability to encode data in both the phase and amplitude of light, thereby increasing the bits/sec/Hz as compared to simple on-off keyed format. Coherent communications has also emerged as a primary means of transmitting and receiving optical data due to its support of formats that utilize both phase and amplitude to further increase the spectral efficiency of the optical channel, including quadrature amplitude modulation (QAM) and quadrature phase shift keying (QPSK). Polarization multiplexing of channels can double capacity by allowing two channels to share the same wavelength by propagating on orthogonal polarization axis and is easily supported in coherent systems where the polarization tracking can be performed in the digital domain. Furthermore, the forthcoming IEEE 100 Gbit/s Ethernet Standard, 802.3ba, provides greater bandwidth, higher data rates, and supports a mixture of modulation formats. In particular, Pol-MUX QPSK is increasingly becoming the industry's format of choice as the high spectral efficiency allows for 100 Gbit/s transmission while still occupying the current 50 GHz/channel allocation of current 10 Gbit/s OOK fiber systems. In this manner, 100 Gbit/s transfer speeds using current fiber links, amplifiers, and filters

  3. Overexpression of HOXA4 and HOXA9 genes promotes self-renewal and contributes to colon cancer stem cell overpopulation.

    Science.gov (United States)

    Bhatlekar, Seema; Viswanathan, Vignesh; Fields, Jeremy Z; Boman, Bruce M

    2018-02-01

    Because HOX genes encode master regulatory transcription factors that regulate stem cells (SCs) during development and aberrant expression of HOX genes occurs in various cancers, our goal was to determine if dysregulation of HOX genes is involved in the SC origin of colorectal cancer (CRC). We previously reported that HOXA4 and HOXD10 are expressed in the colonic SC niche and are overexpressed in CRC. HOX gene expression was studied in SCs from human colon tissue and CRC cells (CSCs) using qPCR and immunostaining. siRNA-mediated knockdown of HOX expression was used to evaluate the role of HOX genes in modulating cancer SC (CSC) phenotype at the level of proliferation, SC marker expression, and sphere formation. All-trans-retinoic-acid (ATRA), a differentiation-inducing agent was evaluated for its effects on HOX expression and CSC growth. We found that HOXA4 and HOXA9 are up-regulated in CRC SCs. siRNA knockdown of HOXA4 and HOXA9 reduced: (i) proliferation and sphere-formation and (ii) gene expression of known SC markers (ALDH1, CD166, LGR5). These results indicate that proliferation and self-renewal ability of CRC SCs are reduced in HOXA4 and HOXA9 knockdown cells. ATRA decreased HOXA4, HOXA9, and HOXD10 expression in parallel with reduction in ALDH1 expression, self-renewal, and proliferation. Overall, our findings indicate that overexpression of HOXA4 and HOXA9 contributes to self-renewal and overpopulation of SCs in CRC. Strategies designed to modulate HOX expression may provide ways to target malignant SCs and to develop more effective therapies for CRC. © 2017 Wiley Periodicals, Inc.

  4. The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential.

    Science.gov (United States)

    Fiorelli, Roberto; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose-Manuel; Raineteau, Olivier

    2013-12-01

    Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self-renewal and multipotential properties in vitro. We demonstrate that a population of GFAP(+) cells that share the morphology and the antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non-proliferative in the intact spinal cord, but incorporate the S-phase marker EdU following spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e., deriving from recombined GFAP-expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self-renewal properties when compared with SVZ-neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co-exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self-renewal properties. Copyright © 2013 Wiley Periodicals, Inc.

  5. Hollow Carbon Nanofiber-Encapsulated Sulfur Cathodes for High Specific Capacity Rechargeable Lithium Batteries

    KAUST Repository

    Zheng, Guangyuan; Yang, Yuan; Cha, Judy J.; Hong, Seung Sae; Cui, Yi

    2011-01-01

    Sulfur has a high specific capacity of 1673 mAh/g as lithium battery cathodes, but its rapid capacity fading due to polysulfides dissolution presents a significant challenge for practical applications. Here we report a hollow carbon nanofiber

  6. Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells

    Science.gov (United States)

    Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

    2014-01-01

    Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK

  7. Test of the hypothesis; a lymphoma stem cells exist which is capable of self-renewal

    DEFF Research Database (Denmark)

    Kjeldsen, Malene Krag

      Test of the hypothesis; a lymphoma stem cell exist which is capable of self-renewal   Malene Krag Pedersen, Karen Dybkaer, Hans E. Johnsen   The Research Laboratory, Department of Haematology, Aalborg Hospital, Århus University   Failure of current therapeutics in the treatment of diffuse large B...... and sustaining cells(1-3). My project is based on studies of stem and early progenitor cells in lymphoid cell lines from patients with advanced DLBCL. The cell lines are world wide recognised and generously provided by Dr. Hans Messner and colleagues.   Hypothesis and aims: A lymphoma stem and progenitor cell...

  8. Discovery of Power-Law Growth in the Self-Renewal of Heterogeneous Glioma Stem Cell Populations.

    Directory of Open Access Journals (Sweden)

    Michiya Sugimori

    Full Text Available Accumulating evidence indicates that cancer stem cells (CSCs drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS forming model, to generate a population in which glioma stem cells (GSCs become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability.To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres. Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone. Log-log plots of distributions of clone sizes yielded a good fit (r>0.90 to a straight line (log(% total clones = k*log(#cells/clone indicating that the system follows a power-law (y = xk with a specific degree exponent (k = -1.42. Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = -1.01 to -1.17. Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law-dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM, suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population.Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous

  9. A Complex Role for FGF-2 in Self-Renewal, Survival, and Adhesion of Human Embryonic Stem Cells

    Czech Academy of Sciences Publication Activity Database

    Eiselleová, L.; Matulka, K.; Kříž, V.; Kunová, M.; Schmidtová, Z.; Neradil, J.; Tichý, B.; Dvořáková, D.; Pospíšilová, Š.; Hampl, Aleš; Dvořák, Petr

    2009-01-01

    Roč. 27, č. 8 (2009), s. 1847-1857 ISSN 1066-5099 Grant - others:GA MŠk(CZ) 1M0538; GA MŠk(CZ) LC06077; EC FP6(XE) LSHG-CT-2006-018739 Program:1M; LC Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : fibroblast growth factor-2 * human ESCs * self-renewal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.747, year: 2009

  10. Heat shock instructs hESCs to exit from the self-renewal program through negative regulation of OCT4 by SAPK/JNK and HSF1 pathway.

    Science.gov (United States)

    Byun, Kyunghee; Kim, Taek-Kyun; Oh, Jeehyun; Bayarsaikhan, Enkhjargal; Kim, Daesik; Lee, Min Young; Pack, Chan-Gi; Hwang, Daehee; Lee, Bonghee

    2013-11-01

    Environmental factors affect self-renewal of stem cells by modulating the components of self-renewal networks. Heat shock, an environmental factor, induces heat shock factors (HSFs), which up-regulate stress response-related genes. However, the link of heat shock to self-renewal of stem cells has not been elucidated yet. Here, we present the direct link of heat shock to a core stem cell regulator, OCT4, in the self-renewal network through SAPK/JNK and HSF1 pathway. We first showed that heat shock initiated differentiation of human embryonic stem cells (hESCs). Gene expression analysis revealed that heat shock increased the expression of many genes involved in cellular processes related to differentiation of stem cells. We then examined the effects of HSFs induced by heat shock on core self-renewal factors. Among HSFs, heat shock induced mainly HSF1 in hESCs. The HSF1 repressed the expression of OCT4, leading to the differentiation of hESCs and the above differentiation-related gene expression change. We further examined the effects of the upstream MAP (mitogen-activated protein) kinases of HSF1 on the repression of OCT4 expression by HSF1. Among the MAP kinases, SAPK/JNK controlled predominantly the repression of the OCT4 expression by HSF1. The direct link of heat shock to the core self-renewal regulator through SAPK/JNK and HSF1 provides a fundamental basis for understanding the effect of heat and other stresses involving activation of HSF1 on the self-renewal program and further controlling differentiation of hESCs in a broad spectrum of stem cell applications using these stresses. © 2013.

  11. Free-space optical communications with peak and average constraints: High SNR capacity approximation

    KAUST Repository

    Chaaban, Anas

    2015-09-07

    The capacity of the intensity-modulation direct-detection (IM-DD) free-space optical channel with both average and peak intensity constraints is studied. A new capacity lower bound is derived by using a truncated-Gaussian input distribution. Numerical evaluation shows that this capacity lower bound is nearly tight at high signal-to-noise ratio (SNR), while it is shown analytically that the gap to capacity upper bounds is a small constant at high SNR. In particular, the gap to the high-SNR asymptotic capacity of the channel under either a peak or an average constraint is small. This leads to a simple approximation of the high SNR capacity. Additionally, a new capacity upper bound is derived using sphere-packing arguments. This bound is tight at high SNR for a channel with a dominant peak constraint.

  12. High-Capacity Cathode Material with High Voltage for Li-Ion Batteries.

    Science.gov (United States)

    Shi, Ji-Lei; Xiao, Dong-Dong; Ge, Mingyuan; Yu, Xiqian; Chu, Yong; Huang, Xiaojing; Zhang, Xu-Dong; Yin, Ya-Xia; Yang, Xiao-Qing; Guo, Yu-Guo; Gu, Lin; Wan, Li-Jun

    2018-03-01

    Electrochemical energy storage devices with a high energy density are an important technology in modern society, especially for electric vehicles. The most effective approach to improve the energy density of batteries is to search for high-capacity electrode materials. According to the concept of energy quality, a high-voltage battery delivers a highly useful energy, thus providing a new insight to improve energy density. Based on this concept, a novel and successful strategy to increase the energy density and energy quality by increasing the discharge voltage of cathode materials and preserving high capacity is proposed. The proposal is realized in high-capacity Li-rich cathode materials. The average discharge voltage is increased from 3.5 to 3.8 V by increasing the nickel content and applying a simple after-treatment, and the specific energy is improved from 912 to 1033 Wh kg -1 . The current work provides an insightful universal principle for developing, designing, and screening electrode materials for high energy density and energy quality. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. High Working Memory Capacity Predicts Less Retrieval Induced Forgetting

    NARCIS (Netherlands)

    Mall, Jonathan T.; Morey, Candice C.

    2013-01-01

    Background : Working Memory Capacity (WMC) is thought to be related to executive control and focused memory search abilities. These two hypotheses make contrasting predictions regarding the effects of retrieval on forgetting. Executive control during memory retrieval is believed to lead to retrieval

  14. Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

    Directory of Open Access Journals (Sweden)

    Daniela M Santos

    Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.

  15. Distinct Stromal Cell Factor Combinations Can Separately Control Hematopoietic Stem Cell Survival, Proliferation, and Self-Renewal

    Directory of Open Access Journals (Sweden)

    Stefan Wohrer

    2014-06-01

    Full Text Available Hematopoietic stem cells (HSCs are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation, and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential are variably supported by different Steel factor (SF-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings point to the molecular basis of HSC control and expansion.

  16. Histone deacetylase inhibition enhances self renewal and cardioprotection by human cord blood-derived CD34 cells.

    Directory of Open Access Journals (Sweden)

    Ilaria Burba

    Full Text Available BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs, have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+ were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+ cells with enhanced self renewal and cardioprotection.

  17. Nac1 promotes self-renewal of embryonic stem cells through direct transcriptional regulation of c-Myc.

    Science.gov (United States)

    Ruan, Yan; He, Jianrong; Wu, Wei; He, Ping; Tian, Yanping; Xiao, Lan; Liu, Gaoke; Wang, Jiali; Cheng, Yuda; Zhang, Shuo; Yang, Yi; Xiong, Jiaxiang; Zhao, Ke; Wan, Ying; Huang, He; Zhang, Junlei; Jian, Rui

    2017-07-18

    The pluripotency transcriptional network in embryonic stem cells (ESCs) is composed of distinct functional units including the core and Myc units. It is hoped that dissection of the cellular functions and interconnections of network factors will aid our understanding of ESC and cancer biology. Proteomic and genomic approaches have identified Nac1 as a member of the core pluripotency network. However, previous studies have predominantly focused on the role of Nac1 in psychomotor stimulant response and cancer pathogenesis. In this study, we report that Nac1 is a self-renewal promoting factor, but is not required for maintaining pluripotency of ESCs. Loss of function of Nac1 in ESCs results in a reduced proliferation rate and an enhanced differentiation propensity. Nac1 overexpression promotes ESC proliferation and delays ESC differentiation in the absence of leukemia inhibitory factor (LIF). Furthermore, we demonstrated that Nac1 directly binds to the c-Myc promoter and regulates c-Myc transcription. The study also revealed that the function of Nac1 in promoting ESC self-renewal appears to be partially mediated by c-Myc. These findings establish a functional link between the core and c-Myc-centered networks and provide new insights into mechanisms of stemness regulation in ESCs and cancer.

  18. On the High Altitude Platform (HAP W-CDMA System Capacity

    Directory of Open Access Journals (Sweden)

    L. de Haro-Ariet

    2004-06-01

    Full Text Available The performance of a downlink power control model, based on a n-thpower distance law, is evaluated for high altitude platform station(HAPS W-CDMA systems. The downlink capacity using this model iscompared with the uplink capacity. It is shown that the uplink capacityis higher than the downlink capacity.

  19. The CCR4 Deadenylase Acts with Nanos and Pumilio in the Fine-Tuning of Mei-P26 Expression to Promote Germline Stem Cell Self-Renewal

    Science.gov (United States)

    Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

    2013-01-01

    Summary Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation. PMID:24286029

  20. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO

    Science.gov (United States)

    Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido

    2012-01-01

    AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

  1. Sevoflurane represses the self-renewal ability by regulating miR-7a,7b/Klf4 signalling pathway in mouse embryonic stem cells.

    Science.gov (United States)

    Wang, Qimin; Li, Guifeng; Li, Baolin; Chen, Qiu; Lv, Dongdong; Liu, Jiaying; Ma, Jieyu; Sun, Nai; Yang, Longqiu; Fei, Xuejie; Song, Qiong

    2016-10-01

    Sevoflurane is a frequently-used clinical inhalational anaesthetic and can cause toxicity to embryos during foetal development. Embryonic stem cells (ESCs) are derived from the inner cell mass of blastospheres and can be used as a useful model of early development. Here, we found that sevoflurane significantly influenced self-renewal ability of mESCs on stemness maintenance and cell proliferation. The cell cycle was arrested via G1 phase delay. We further found that sevoflurane upregulated expression of miR-7a,7b to repress self-renewal. Next we performed rescue experiments and found that after adding miR-7a,7b inhibitor into mESCs treated with sevoflurane, its influence on self-renewal could be blocked. Further we identified stemness factor Klf4 as the direct target of miR-7a,7b. Overexpression of Klf4 restored self-renewal ability repressed by miR-7a,7b or sevoflurane. In this work, we determined that sevoflurane repressed self-renewal ability by regulating the miR-7a,7b/Klf4 signalling pathway in mESCs. Our study demonstrated molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on safe usage of inhalational anaesthetic during non-obstetric surgery. © 2016 John Wiley & Sons Ltd.

  2. The CCR4 deadenylase acts with Nanos and Pumilio in the fine-tuning of Mei-P26 expression to promote germline stem cell self-renewal.

    Science.gov (United States)

    Joly, Willy; Chartier, Aymeric; Rojas-Rios, Patricia; Busseau, Isabelle; Simonelig, Martine

    2013-01-01

    Translational regulation plays an essential role in Drosophila ovarian germline stem cell (GSC) biology. GSC self-renewal requires two translational repressors, Nanos (Nos) and Pumilio (Pum), which repress the expression of differentiation factors in the stem cells. The molecular mechanisms underlying this translational repression remain unknown. Here, we show that the CCR4 deadenylase is required for GSC self-renewal and that Nos and Pum act through its recruitment onto specific mRNAs. We identify mei-P26 mRNA as a direct and major target of Nos/Pum/CCR4 translational repression in the GSCs. mei-P26 encodes a protein of the Trim-NHL tumor suppressor family that has conserved functions in stem cell lineages. We show that fine-tuning Mei-P26 expression by CCR4 plays a key role in GSC self-renewal. These results identify the molecular mechanism of Nos/Pum function in GSC self-renewal and reveal the role of CCR4-NOT-mediated deadenylation in regulating the balance between GSC self-renewal and differentiation.

  3. Crystalline-Amorphous Core−Shell Silicon Nanowires for High Capacity and High Current Battery Electrodes

    KAUST Repository

    Cui, Li-Feng

    2009-01-14

    Silicon is an attractive alloy-type anode material for lithium ion batteries because of its highest known capacity (4200 mAh/g). However silicon\\'s large volume change upon lithium insertion and extraction, which causes pulverization and capacity fading, has limited its applications. Designing nanoscale hierarchical structures is a novel approach to address the issues associated with the large volume changes. In this letter, we introduce a core-shell design of silicon nanowires for highpower and long-life lithium battery electrodes. Silicon crystalline- amorphous core-shell nanowires were grown directly on stainless steel current collectors by a simple one-step synthesis. Amorphous Si shells instead of crystalline Si cores can be selected to be electrochemically active due to the difference of their lithiation potentials. Therefore, crystalline Si cores function as a stable mechanical support and an efficient electrical conducting pathway while amorphous shells store Li ions. We demonstrate here that these core-shell nanowires have high charge storage capacity (̃1000 mAh/g, 3 times of carbon) with ̃90% capacity retention over 100 cycles. They also show excellent electrochemical performance at high rate charging and discharging (6.8 A/g, ̃20 times of carbon at 1 h rate). © 2009 American Chemical Society.

  4. OTDM Networking for Short Range High-Capacity Highly Dynamic Networks

    DEFF Research Database (Denmark)

    Medhin, Ashenafi Kiros

    This PhD thesis aims at investigating the possibility of designing energy-efficient high-capacity (up to Tbit/s) optical network scenarios, leveraging on the effect of collective switching of many bits simultaneously, as is inherent in high bit rate serial optical data signals. The focus...... is on short range highly dynamic networks, catering to data center needs. The investigation concerns optical network scenarios, and experimental implementations of high bit rate serial data packet generation and reception, scalable optical packet labeling, simple optical label extraction and stable ultra...

  5. Remapping high-capacity, pre-attentive, fragile sensory memory.

    Science.gov (United States)

    Zerr, Paul; Gayet, Surya; Mulder, Kees; Pinto, Yaïr; Sligte, Ilja; Van der Stigchel, Stefan

    2017-11-21

    Humans typically make several saccades per second. This provides a challenge for the visual system as locations are largely coded in retinotopic (eye-centered) coordinates. Spatial remapping, the updating of retinotopic location coordinates of items in visuospatial memory, is typically assumed to be limited to robust, capacity-limited and attention-demanding working memory (WM). Are pre-attentive, maskable, sensory memory representations (e.g. fragile memory, FM) also remapped? We directly compared trans-saccadic WM (tWM) and trans-saccadic FM (tFM) in a retro-cue change-detection paradigm. Participants memorized oriented rectangles, made a saccade and reported whether they saw a change in a subsequent display. On some trials a retro-cue indicated the to-be-tested item prior to probe onset. This allowed sensory memory items to be included in the memory capacity estimate. The observed retro-cue benefit demonstrates a tFM capacity considerably above tWM. This provides evidence that some, if not all sensory memory was remapped to spatiotopic (world-centered, task-relevant) coordinates. In a second experiment, we show backward masks to be effective in retinotopic as well as spatiotopic coordinates, demonstrating that FM was indeed remapped to world-centered coordinates. Together this provides conclusive evidence that trans-saccadic spatial remapping is not limited to higher-level WM processes but also occurs for sensory memory representations.

  6. Construction and Capacity Analysis of High-Rank LoS MIMO Channels in High Speed Railway Scenarios

    Directory of Open Access Journals (Sweden)

    Jingya Yang

    2012-01-01

    Full Text Available The validity of the maximum capacity criterion applied to realize high-rank line-of-sight (LoS multiple-input multiple-output (MIMO channels is investigated for high speed railway scenarios. Performance is evaluated by ergodic capacity. Numerical results demonstrate that by simply adjusting antenna spacing according to the maximum capacity criterion, significant capacity gains are achievable. We find relatively low sensitivity of the system to displacements from the optimal point and angle in relatively short range. Thus, we present two proposals to reconfigure antenna arrays so as to maximize LoS MIMO capacity in the high speed railway scenarios

  7. Free-space optical communications with peak and average constraints: High SNR capacity approximation

    KAUST Repository

    Chaaban, Anas; Morvan, Jean-Marie; Alouini, Mohamed-Slim

    2015-01-01

    . Numerical evaluation shows that this capacity lower bound is nearly tight at high signal-to-noise ratio (SNR), while it is shown analytically that the gap to capacity upper bounds is a small constant at high SNR. In particular, the gap to the high

  8. Porous graphene for high capacity lithium ion battery anode material

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yusheng, E-mail: xxwysheng@163.com [College of Mathematics and Information Science, North China University of Water Resources and Electric Power, Zhengzhou 450011 (China); School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001 (China); Zhang, Qiaoli; Jia, Min; Yang, Dapeng [College of Mathematics and Information Science, North China University of Water Resources and Electric Power, Zhengzhou 450011 (China); Wang, Jianjun; Li, Meng [College of Science, Zhongyuan University of Technology, Zhengzhou 450007 (China); Zhang, Jing [College of Mathematics and Information Science, North China University of Water Resources and Electric Power, Zhengzhou 450011 (China); Sun, Qiang [School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001 (China); Jia, Yu, E-mail: jiayu@zzu.edu.cn [School of Physics and Engineering, Zhengzhou University, Zhengzhou 450001 (China)

    2016-02-15

    Graphical abstract: - Highlights: • Porous graphene sheet as Li storage media. • Excellent mobility both along in-plane and out-plane directions. • The interactions can be easily tuned by an applied strain. - Abstract: Based on density functional theory calculations, we studied the Li dispersed on porous graphene (PG) for its application as Li ion battery anode material. The hybridization of Li atoms and the carbon atoms enhanced the interaction between Li atoms and the PG. With holes of specific size, the PG can provide excellent mobility with moderate barriers of 0.37–0.39 eV. The highest Li storage composite can be LiC{sub 0.75}H{sub 0.38} which corresponds to a specific capacity of 2857.7 mA h/g. Both specific capacity and binding energy are significantly larger than the corresponding value of graphite, this makes PG a promising candidate for the anode material in battery applications. The interactions between the Li atoms and PG can be easily tuned by an applied strain. Under biaxial strain of 16%, the binding energy of Li to PG is increased by 17% compared to its unstrained state.

  9. Pleiotropy of Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Self-Renewal of Embryonic Stem Cells from Refractory Mouse Strains

    Science.gov (United States)

    Ye, Shoudong; Tan, Li; Yang, Rongqing; Fang, Bo; Qu, Su; Schulze, Eric N.; Song, Houyan; Ying, Qilong; Li, Ping

    2012-01-01

    Background Inhibition of glycogen synthase kinase-3 (GSK-3) improves the efficiency of embryonic stem (ES) cell derivation from various strains of mice and rats, as well as dramatically promotes ES cell self-renewal potential. β-catenin has been reported to be involved in the maintenance of self-renewal of ES cells through TCF dependent and independent pathway. But the intrinsic difference between ES cell lines from different species and strains has not been characterized. Here, we dissect the mechanism of GSK-3 inhibition by CHIR99021 in mouse ES cells from refractory mouse strains. Methodology/Principal Findings We found that CHIR99021, a GSK-3 specific inhibitor, promotes self-renewal of ES cells from recalcitrant C57BL/6 (B6) and BALB/c mouse strains through stabilization of β-catenin and c-Myc protein levels. Stabilized β-catenin promoted ES self-renewal through two mechanisms. First, β-catenin translocated into the nucleus to maintain stem cell pluripotency in a lymphoid-enhancing factor/T-cell factor–independent manner. Second, β-catenin binds plasma membrane-localized E-cadherin, which ensures a compact, spherical morphology, a hallmark of ES cells. Further, elevated c-Myc protein levels did not contribute significantly to CH-mediated ES cell self-renewal. Instead, the role of c-Myc is dependent on its transformation activity and can be replaced by N-Myc but not L-Myc. β-catenin and c-Myc have similar effects on ES cells derived from both B6 and BALB/c mice. Conclusions/Significance Our data demonstrated that GSK-3 inhibition by CH promotes self-renewal of mouse ES cells with non-permissive genetic backgrounds by regulation of multiple signaling pathways. These findings would be useful to improve the availability of normally non-permissive mouse strains as research tools. PMID:22540008

  10. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal.

    Science.gov (United States)

    Yan, Kelley S; Janda, Claudia Y; Chang, Junlei; Zheng, Grace X Y; Larkin, Kathryn A; Luca, Vincent C; Chia, Luis A; Mah, Amanda T; Han, Arnold; Terry, Jessica M; Ootani, Akifumi; Roelf, Kelly; Lee, Mark; Yuan, Jenny; Li, Xiao; Bolen, Christopher R; Wilhelmy, Julie; Davies, Paige S; Ueno, Hiroo; von Furstenberg, Richard J; Belgrader, Phillip; Ziraldo, Solongo B; Ordonez, Heather; Henning, Susan J; Wong, Melissa H; Snyder, Michael P; Weissman, Irving L; Hsueh, Aaron J; Mikkelsen, Tarjei S; Garcia, K Christopher; Kuo, Calvin J

    2017-05-11

    The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium-an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5 + intestinal stem cells (ISCs). R-spondin ligands (RSPO1-RSPO4) engage distinct LGR4-LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5 + ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5 + ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5 + ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction

  11. Economic viability of transmission capacity expansion at high wind penetrations

    DEFF Research Database (Denmark)

    Østergaard, Poul Alberg

    2005-01-01

    investments and analyses of the Nord Pool price variations. The analyses are done for varying degrees of wind power penetrations ranging from 20% of the West Danish electricity demand up to 100% of the demand. The analyses demonstrate, that while there is an economic potential for some expansion in some years......With growing wind power penetrations in many countries, grid and system integration becomes more and more important issues. This is particularly the case in countries or regions with good wind resources as well as substantial installed wind power capacity as found in e.g. Northern Europe. At 20......% penetration in Western Denmark, the issue is pertinent here in relation to future plans of further expansion which is planned in accordance with the Danish Government’s climate change mitigation initiatives. This paper analyses the potential economic benefit of selling excess electricity production...

  12. Burnup credit applications in a high-capacity truck cask

    International Nuclear Information System (INIS)

    Boshoven, J.K.

    1993-01-01

    The use of burnup credit in the criticality safety analysis of the GA-4 Cask increases the cask's capacity from three spent fuel assemblies to four, resulting in reduced public and occupational risk and reduced life cycle costs. GA's criticality calculations for burnup credit, including the associated uncertainties and analytical bias, establish the minimum burnup required as a function of initial enrichment to maintain K eff ≤ 0.95 under any conceivable condition. The minimum burnup requirement as a function of initial enrichment has been determined to be 15,000 MWd/MTU for 3.5 wt% U-235 fuel, 20,000 MWd/MTU for 4.0 wt% U-235 fuel and 25,000 MWd/MTU for 4.5 wt% U-235 fuel. The minimum burnup requirement as a function of enrichment is well below the typical burnup levels seen in the current and projected spent fuel inventory. (J.P.N.)

  13. High capacity adsorption media and method of producing

    Science.gov (United States)

    Tranter, Troy J.; Mann, Nicholas R.; Todd, Terry A.; Herbst, Ronald S.

    2010-10-05

    A method of producing an adsorption medium to remove at least one constituent from a feed stream. The method comprises dissolving and/or suspending at least one metal compound in a solvent to form a metal solution, dissolving polyacrylonitrile into the metal solution to form a PAN-metal solution, and depositing the PAN-metal solution into a quenching bath to produce the adsorption medium. The at least one constituent, such as arsenic, selenium, or antimony, is removed from the feed stream by passing the feed stream through the adsorption medium. An adsorption medium having an increased metal loading and increased capacity for arresting the at least one constituent to be removed is also disclosed. The adsorption medium includes a polyacrylonitrile matrix and at least one metal hydroxide incorporated into the polyacrylonitrile matrix.

  14. MIMO Intensity-Modulation Channels: Capacity Bounds and High SNR Characterization

    KAUST Repository

    Chaaban, Anas

    2016-10-01

    The capacity of MIMO intensity modulation channels is studied. The nonnegativity of the transmit signal (intensity) poses a challenge on the precoding of the transmit signal, which limits the applicability of classical schemes in this type of channels. To resolve this issue, capacity lower bounds are developed by using precoding-free schemes. This is achieved by channel inversion or QR decomposition to convert the MIMO channel to a set of parallel channels. The achievable rate of a DC-offset SVD based scheme is also derived as a benchmark. Then, a capacity upper bound is derived and is shown to coincide with the achievable rate of the QR decomposition based scheme at high SNR, consequently characterizing the high-SNR capacity of the channel. The high-SNR gap between capacity and the achievable rates of the channel inversion and the DC-offset SVD based schemes is also characterized. Finally, the ergodic capacity of the channel is also briefly discussed.

  15. High-capacity, selective solid sequestrants for innovative chemical separation: Inorganic ion exchange approach

    International Nuclear Information System (INIS)

    Bray, L.

    1995-01-01

    The approach of this task is to develop high-capacity, selective solid inorganic ion exchangers for the recovery of cesium and strontium from nuclear alkaline and acid wastes. To achieve this goal, Pacific Northwest Laboratories (PNL) is collaborating with industry and university participants to develop high capacity, selective, solid ion exchangers for the removal of specific contaminants from nuclear waste streams

  16. Pleiotrophin Regulates the Retention and Self-Renewal of Hematopoietic Stem Cells in the Bone Marrow Vascular Niche

    Directory of Open Access Journals (Sweden)

    Heather A. Himburg

    2012-10-01

    Full Text Available The mechanisms through which the bone marrow (BM microenvironment regulates hematopoietic stem cell (HSC fate remain incompletely understood. We examined the role of the heparin-binding growth factor pleiotrophin (PTN in regulating HSC function in the niche. PTN−/− mice displayed significantly decreased BM HSC content and impaired hematopoietic regeneration following myelosuppression. Conversely, mice lacking protein tyrosine phosphatase receptor zeta, which is inactivated by PTN, displayed significantly increased BM HSC content. Transplant studies revealed that PTN action was not HSC autonomous, but rather was mediated by the BM microenvironment. Interestingly, PTN was differentially expressed and secreted by BM sinusoidal endothelial cells within the vascular niche. Furthermore, systemic administration of anti-PTN antibody in mice substantially impaired both the homing of hematopoietic progenitor cells to the niche and the retention of BM HSCs in the niche. PTN is a secreted component of the BM vascular niche that regulates HSC self-renewal and retention in vivo.

  17. R-spondin1/Wnt-enhanced Ascl2 autoregulation controls the self-renewal of colorectal cancer progenitor cells.

    Science.gov (United States)

    Ye, Jun; Liu, Shanxi; Shang, Yangyang; Chen, Haoyuan; Wang, Rongquan

    2018-06-25

    The Wnt signaling pathway controls stem cell identity in the intestinal epithelium and cancer stem cells (CSCs). The transcription factor Ascl2 (Wnt target gene) is fate decider of intestinal cryptic stem cells and colon cancer stem cells. It is unclear how Wnt signaling is translated into Ascl2 expression and keeping the self-renewal of CRC progenitor cells. We showed that the exogenous Ascl2 in colorectal cancer (CRC) cells activated the endogenous Ascl2 expression via a direct autoactivatory loop, including Ascl2 binding to its own promoter and further transcriptional activation. Higher Ascl2 expression in human CRC cancerous tissues led to greater enrichment in Ascl2 immunoprecipitated DNA within the Ascl2 promoter in the CRC cancerous sample than the peri-cancerous mucosa. Ascl2 binding to its own promoter and inducing further transcriptional activation of the Ascl2 gene was predominant in the CD133 + CD44 + CRC population. R-spondin1/Wnt activated Ascl2 expression dose-dependently in the CD133 + CD44 + CRC population, but not in the CD133 - CD44 - CRC population, which was caused by differences in Ascl2 autoregulation under R-spondin1/Wnt activation. R-spondin1/Wnt treatment in the CD133 + CD44 + or CRC CD133 - CD44 - populations exerted a different pattern of stemness maintenance, which was defined by alterations of the mRNA levels of stemness-associated genes, the protein expression levels (Bmi1, C-myc, Oct-4 and Nanog) and tumorsphere formation. The results indicated that Ascl2 autoregulation formed a transcriptional switch that was enhanced by Wnt signaling in the CD133 + CD44 + CRC population, thus conferring their self-renewal.

  18. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-05-01

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774. © AlphaMed Press 2018.

  19. Why high-capacity manipulators and lead glass windows

    International Nuclear Information System (INIS)

    Grisham, D.L.; Lambert, J.E.

    1981-01-01

    The Monitor remote-handling system was developed to maintain the main experimental beam line at the Clinton P. Anderson Meson Physics Facility (LAMPF) of the Los Alamos National Laboratory. The technology and operating experience developed at LAMPF can be applied to other areas where handling of radioactive, hazardous, or toxic materials is required. These could include radiological incidents similar to Three Mile Island and toxic material spills, such as chlorine tank car derailments, where no provision for remote-handling exists. The technology can also be applied to routine radioactive remote-handling operations now conducted in conventional hot cells. These operations are normally done using mechanical master-slave manipulators with viewing through lead glass windows. The conventional facility can be replaced by a plain shielded box with an equivalent of the front end of Monitor inside. Master-slave manipulators of the future should be of 10-kg capacity with a force-reflection threshold of 0.2, minimum size, and provision for total sealing

  20. Selection of local extremophile lactic acid bacteria with high capacity ...

    African Journals Online (AJOL)

    This study is related to the isolation and identification of strains of local thermophilic lactic acid bacteria belonging to the species, Streptococcus thermophilus and Lactobacillus bulgaricus. These bacteria can exist under extreme conditions of the digestive tract (acidity and high concentration of bile salts) and have a high ...

  1. High throughput assay for evaluation of reactive carbonyl scavenging capacity.

    Science.gov (United States)

    Vidal, N; Cavaille, J P; Graziani, F; Robin, M; Ouari, O; Pietri, S; Stocker, P

    2014-01-01

    Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.

  2. High throughput assay for evaluation of reactive carbonyl scavenging capacity

    Directory of Open Access Journals (Sweden)

    N. Vidal

    2014-01-01

    Full Text Available Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.

  3. A regulatory network of Drosophila germline stem cell self-renewal

    OpenAIRE

    Yan, Dong; Neumüller, Ralph A.; Buckner, Michael; Ayers, Kathleen; Li, Hua; Hu, Yanhui; Yang-Zhou, Donghui; Pan, Lei; Wang, Xiaoxi; Kelley, Colleen; Vinayagam, Arunachalam; Binari, Richard; Randklev, Sakara; Perkins, Lizabeth A.; Xie, Ting

    2014-01-01

    Stem cells possess the capacity to generate two cells of distinct fate upon division; one cell retaining stem cell identity and the other cell destined to differentiate. These cell fates are established by cell-type-specific genetic networks. To comprehensively identify components of these networks, we performed a large-scale RNAi screen in Drosophila female germline stem cells (GSCs) covering ~25% of the genome. The screen identified 366 genes that affect GSC maintenance, differentiation or ...

  4. Silicon oxide based high capacity anode materials for lithium ion batteries

    Science.gov (United States)

    Deng, Haixia; Han, Yongbong; Masarapu, Charan; Anguchamy, Yogesh Kumar; Lopez, Herman A.; Kumar, Sujeet

    2017-03-21

    Silicon oxide based materials, including composites with various electrical conductive compositions, are formulated into desirable anodes. The anodes can be effectively combined into lithium ion batteries with high capacity cathode materials. In some formulations, supplemental lithium can be used to stabilize cycling as well as to reduce effects of first cycle irreversible capacity loss. Batteries are described with surprisingly good cycling properties with good specific capacities with respect to both cathode active weights and anode active weights.

  5. The effect of angiotensin converting enzyme genotype on aerobic capacity following high intensity interval training

    OpenAIRE

    Goddard, N; Baker, M.D; Higgins, T; Cobbold, C

    2014-01-01

    Obesity increases the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Physical activity can reduce T2DM and CVD risk, and increase aerobic capacity, a significant predictor of all-cause mortality and morbidity. High intensity interval training (HIIT) produces similar improvements in aerobic capacity to continuous moderate exercise (CME). Different genotypes of angiotensin converting enzyme (ACE) have been implicated in improving aerobic capacity and theref...

  6. Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.

    Science.gov (United States)

    Sansone, Pasquale; Ceccarelli, Claudio; Berishaj, Marjan; Chang, Qing; Rajasekhar, Vinagolu K; Perna, Fabiana; Bowman, Robert L; Vidone, Michele; Daly, Laura; Nnoli, Jennifer; Santini, Donatella; Taffurelli, Mario; Shih, Natalie N C; Feldman, Michael; Mao, Jun J; Colameco, Christopher; Chen, Jinbo; DeMichele, Angela; Fabbri, Nicola; Healey, John H; Cricca, Monica; Gasparre, Giuseppe; Lyden, David; Bonafé, Massimiliano; Bromberg, Jacqueline

    2016-02-09

    The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy.

  7. Comprehensive analysis of miRNAs expression profiles revealed potential key miRNA/mRNAs regulating colorectal cancer stem cell self-renewal.

    Science.gov (United States)

    Xu, Peng; Wang, Junhua; Sun, Bo; Xiao, Zhongdang

    2018-05-20

    Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood. Recently, miRNAs are reported to be relevant to the self-renewal ability of cancer stem cells. In this study, we first isolated colorectal cancer stem cell from colorectal cancer cell line HCT-116 by 1% low serum culture. Then we conducted a comprehensive analysis based on the miRNAs profiles data of both colorectal cancer stem cells and normal cultured colorectal cancer cells. Pathway analysis revealed multiple pathways including Jak-STAT, TGF-beta, PI3K-Akt and MAPK signaling pathway that are correlated to colorectal cancer. Further, we constructed a miRNA-mRNA network, based on which, several miRNA/mRNA pairs were ranked according to their impact index to the self-renewal of colorectal cancer stem cells. Further biological experiment showed that up-regulation of miR-92a-3p led to cell cycle arrest and reduced colony formation. This work provides clues to find the new potential biomarkers for colorectal cancer stem cell diagnosis and select effective miRNAs for targeted therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. bHLH-O proteins balance the self-renewal and differentiation of Drosophila neural stem cells by regulating Earmuff expression.

    Science.gov (United States)

    Li, Xiaosu; Chen, Rui; Zhu, Sijun

    2017-11-15

    Balancing self-renewal and differentiation of stem cells requires differential expression of self-renewing factors in two daughter cells generated from the asymmetric division of the stem cells. In Drosophila type II neural stem cell (or neuroblast, NB) lineages, the expression of the basic helix-loop-helix-Orange (bHLH-O) family proteins, including Deadpan (Dpn) and E(spl) proteins, is required for maintaining the self-renewal and identity of type II NBs, whereas the absence of these self-renewing factors is essential for the differentiation of intermediate neural progenitors (INPs) generated from type II NBs. Here, we demonstrate that Dpn maintains type II NBs by suppressing the expression of Earmuff (Erm). We provide evidence that Dpn and E(spl) proteins suppress Erm by directly binding to C-sites and N-boxes in the cis-regulatory region of erm. Conversely, the absence of bHLH-O proteins in INPs allows activation of erm and Erm-mediated maturation of INPs. Our results further suggest that Pointed P1 (PntP1) mediates the dedifferentiation of INPs resulting from the loss of Erm or overexpression of Dpn or E(spl) proteins. Taken together, these findings reveal mechanisms underlying the regulation of the maintenance of type II NBs and differentiation of INPs through the differential expression of bHLH-O family proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice

    NARCIS (Netherlands)

    Bruggeman, SWM; Valk-Lingbeek, ME; van der Stoop, PPM; Jacobs, JJL; Kieboom, K; Tanger, E; Hulsman, D; Leung, C; Arsenijevic, Y; Marino, S; van Lohuizen, M

    2005-01-01

    The Polycomb group (PcG) gene Bmi1 promotes cell proliferation and stem cell self-renewal by repressing the Ink4a/Arf locus. We used a genetic approach to investigate whether Ink4a or Arf is more critical for relaying Bmi1 function in lymphoid cells, neural progenitors, and neural stem cells. We

  10. The cell cycle inhibitor p27Kip¹ controls self-renewal and pluripotency of human embryonic stem cells by regulating the cell cycle, Brachyury and Twist.

    Science.gov (United States)

    Menchón, Cristina; Edel, Michael J; Izpisua Belmonte, Juan Carlos

    2011-05-01

    The continued turn over of human embryonic stem cells (hESC) while maintaining an undifferentiated state is dependent on the regulation of the cell cycle. Here we asked the question if a single cell cycle gene could regulate the self-renewal or pluripotency properties of hESC. We identified that the protein expression of the p27(Kip)¹ cell cycle inhibitor is low in hESC cells and increased with differentiation. By adopting a gain and loss of function strategy we forced or reduced its expression in undifferentiating conditions to define its functional role in self-renewal and pluripotency. Using undifferentiation conditions, overexpression of p27(Kip)¹ in hESC lead to a G₁phase arrest with an enlarged and flattened hESC morphology and consequent loss of self-renewal ability. Loss of p27(Kip)¹ caused an elongated/scatter cell-like phenotype involving up-regulation of Brachyury and Twist gene expression. We demonstrate the novel finding that p27(Kip)¹ protein occupies the Twist1 gene promoter and manipulation of p27(Kip)¹ by gain and loss of function is associated with Twist gene expression changes. These results define p27(Kip)¹ expression levels as critical for self-renewal and pluripotency in hESC and suggest a role for p27(Kip)¹ in controlling an epithelial to mesenchymal transition (EMT) in hESC.

  11. Inhibition of Wnt/β-catenin signaling by IWR1 induces expression of Foxd3 to promote mouse epiblast stem cell self-renewal.

    Science.gov (United States)

    Liu, Kuisheng; Sun, Yuanyuan; Liu, Dahai; Ye, Shoudong

    2017-08-26

    Inhibition of Wnt/β-catenin signaling facilitates the derivation of mouse epiblast stem cells (EpiSCs), as well as dramatically promotes EpiSC self-renewal. The specific mechanism, however, is still unclear. Here, we showed that IWR1, a Wnt/β-catenin signaling inhibitor, allowed long-term self-renewal of EpiSCs in serum medium in combination with ROCK inhibitor Y27632. Through transcriptome data analysis, we arrived at a set of candidate transcription factors induced by IWR1. Among these, Forkhead box D3 (Foxd3) was most abundant. Forced expression of Foxd3 could recapitulate the self-renewal-promoting effect of IWR1 in EpiSCs. Conversely, knockdown of Foxd3 profoundly compromised responsiveness to IWR1, causing extinction of pluripotency markers and emergence of differentiation phenotype. Foxd3 thus is necessary and sufficient to mediate self-renewal downstream of Wnt/β-catenin signaling inhibitor. These findings highlight an important role for Foxd3 in regulating EpiSCs and will expand current understanding of the primed pluripotency. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Irradiation-injured brain tissues can self-renew in the absence of the pivotal tumor suppressor p53 in the medaka (Oryzias latipes) embryo

    International Nuclear Information System (INIS)

    Yasuda, Takako; Nagata, Kento; Igarashi, Kento; Watanabe-Asaka, Tomomi; Oda, Shoji; Mitani, Hiroshi; Kimori, Yoshitaka

    2016-01-01

    The tumor suppressor protein, p53, plays pivotal roles in regulating apoptosis and proliferation in the embryonic and adult central nervous system (CNS) following neuronal injuries such as those induced by ionizing radiation. There is increasing evidence that p53 negatively regulates the self-renewal of neural stem cells in the adult murine brain; however, it is still unknown whether p53 is essential for self-renewal in the injured developing CNS. Previously, we demonstrated that the numbers of apoptotic cells in medaka (Oryzias latipes) embryos decreased in the absence of p53 at 12-24 h after irradiation with 10-Gy gamma rays. Here, we used histology to examine the later morphological development of the irradiated medaka brain. In p53-deficient larvae, the embryonic brain possessed similar vacuoles in the brain and retina, although the vacuoles were much smaller and fewer than those found in wild-type embryos. At the time of hatching (6 days after irradiation), no brain abnormality was observed. In contrast, severe disorganized neuronal arrangements were still present in the brain of irradiated wild-type embryos. Our present results demonstrated that self-renewal of the brain tissue completed faster in the absence of p53 than wild type at the time of hatching because p53 reduces the acute severe neural apoptosis induced by irradiation, suggesting that p53 is not essential for tissue self-renewal in developing brain. (author)

  13. High-Capacity Short-Range Optical Communication Links

    DEFF Research Database (Denmark)

    Tatarczak, Anna

    Over the last decade, we have observed a tremendous spread of end-user mobile devices. The user base of a mobile application can grow or shrink by millions per day. This situation creates a pressing need for highly scalable server infrastructure; a need nowadays satisfied through cloud computing...... offered by data centers. As the popularity of cloud computing soars, the demand for high-speed, short-range data center links grows. Vertical cavity surface emitting lasers (VCSEL) and multimode fibers (MMF) prove especially well-suited for such scenarios. VCSELs have high modulation bandwidths......, we achieve 10 Gbps over 400 m and then conrm the approach in an optimized system at 25 Gbps over 300 m. The techniques described in this thesis leverage additional degrees of freedom to better utilize the available resources of short-range links. The proposed schemes enable higher speeds and longer...

  14. High-capacity electrode materials for electrochemical energy storage

    Indian Academy of Sciences (India)

    2015-06-02

    Jun 2, 2015 ... We discuss the role of nanoscale effects on the electrochemical ..... tems and BASF for developing high energy density lithium ion cells for plug-in electric ..... SEM and STEM images showing typical shapes and sizes of FeF2 ...

  15. Beyond the magic number four: Remapping high-capacity, pre-attentive, fragile working memory

    NARCIS (Netherlands)

    Zerr, P.; Gayet, S.; Mulder, K.T.; Sligte, I.G.; Stigchel, S. van der

    2017-01-01

    Visual short term memory allows us to access visual information after termination of its retinal input. Generally, a distinction is made between a robust, capacity-limited form (working memory, WM) and high-capacity, pre-attentive, maskable forms (sensory memory, e.g. fragile memory, FM). Eye

  16. Comprehensive Identification of Krüppel-Like Factor Family Members Contributing to the Self-Renewal of Mouse Embryonic Stem Cells and Cellular Reprogramming.

    Directory of Open Access Journals (Sweden)

    Hyojung Jeon

    Full Text Available Pluripotency is maintained in mouse embryonic stem (ES cells and is induced from somatic cells by the activation of appropriate transcriptional regulatory networks. Krüppel-like factor gene family members, such as Klf2, Klf4 and Klf5, have important roles in maintaining the undifferentiated state of mouse ES cells as well as in cellular reprogramming, yet it is not known whether other Klf family members exert self-renewal and reprogramming functions when overexpressed. In this study, we examined whether overexpression of any representative Klf family member, such as Klf1-Klf10, would be sufficient for the self-renewal of mouse ES cells. We found that only Klf2, Klf4, and Klf5 produced leukemia inhibitory factor (LIF-independent self-renewal, although most KLF proteins, if not all, have the ability to occupy the regulatory regions of Nanog, a critical Klf target gene. We also examined whether overexpression of any of Klf1-Klf10 would be sufficient to convert epiblast stem cells into a naïve pluripotent state and found that Klf5 had such reprogramming ability, in addition to Klf2 and Klf4. We also delineated the functional domains of the Klf2 protein for LIF-independent self-renewal and reprogramming. Interestingly, we found that both the N-terminal transcriptional activation and C-terminal zinc finger domains were indispensable for this activity. Taken together, our comprehensive analysis provides new insight into the contribution of Klf family members to mouse ES self-renewal and cellular reprogramming.

  17. Comprehensive Identification of Krüppel-Like Factor Family Members Contributing to the Self-Renewal of Mouse Embryonic Stem Cells and Cellular Reprogramming.

    Science.gov (United States)

    Jeon, Hyojung; Waku, Tsuyoshi; Azami, Takuya; Khoa, Le Tran Phuc; Yanagisawa, Jun; Takahashi, Satoru; Ema, Masatsugu

    2016-01-01

    Pluripotency is maintained in mouse embryonic stem (ES) cells and is induced from somatic cells by the activation of appropriate transcriptional regulatory networks. Krüppel-like factor gene family members, such as Klf2, Klf4 and Klf5, have important roles in maintaining the undifferentiated state of mouse ES cells as well as in cellular reprogramming, yet it is not known whether other Klf family members exert self-renewal and reprogramming functions when overexpressed. In this study, we examined whether overexpression of any representative Klf family member, such as Klf1-Klf10, would be sufficient for the self-renewal of mouse ES cells. We found that only Klf2, Klf4, and Klf5 produced leukemia inhibitory factor (LIF)-independent self-renewal, although most KLF proteins, if not all, have the ability to occupy the regulatory regions of Nanog, a critical Klf target gene. We also examined whether overexpression of any of Klf1-Klf10 would be sufficient to convert epiblast stem cells into a naïve pluripotent state and found that Klf5 had such reprogramming ability, in addition to Klf2 and Klf4. We also delineated the functional domains of the Klf2 protein for LIF-independent self-renewal and reprogramming. Interestingly, we found that both the N-terminal transcriptional activation and C-terminal zinc finger domains were indispensable for this activity. Taken together, our comprehensive analysis provides new insight into the contribution of Klf family members to mouse ES self-renewal and cellular reprogramming.

  18. Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem cells: a model of molecular convergence for stemness.

    Science.gov (United States)

    Hong, Sung-Hyun; Yang, Seung-Jip; Kim, Tae-Min; Shim, Jae-Seung; Lee, Ho-Sun; Lee, Ga-Young; Park, Bo-Bae; Nam, Suk Woo; Ryoo, Zae Young; Oh, Il-Hoan

    2014-05-01

    The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells (HSCs) without overriding the normal stem cell pool size. A similar enhancement of HSC self-renewal occurs when signal transducer and activator of transcription 3 (STAT3) is activated in HSCs. In this study, to gain insight into the functional organization of individual transcription factors (TFs) that have similar effects on HSCs, we investigated the molecular interplay between HoxB4 and STAT3 in the regulation of HSC self-renewal. We found that while STAT3-C or HoxB4 similarly enhanced the in vitro self-renewal and in vivo repopulating activities of HSCs, simultaneous transduction of both TFs did not have additive effects, indicating their functional redundancy in HSCs. In addition, activation of STAT3 did not cause changes in the expression levels of HoxB4. In contrast, the inhibition of STAT3 activity in HoxB4-overexpressing hematopoietic cells significantly abrogated the enhancing effects of HoxB4, and the upregulation of HoxB4 caused a ligand-independent Tyr-phosphorylation of STAT3. Microarray analysis revealed a significant overlap of the transcriptomes regulated by STAT3 and HoxB4 in undifferentiated hematopoietic cells. Moreover, a gene set enrichment analysis showed significant overlap in the candidate TFs that can recapitulate the transcriptional changes induced by HoxB4 or STAT3. Interestingly, among these common TFs were the pluripotency-related genes Oct-4 and Nanog. These results indicate that tissue-specific TFs regulating HSC self-renewal are functionally organized to play an equivalent role in transcription and provide insights into the functional convergence of multiple entries of TFs toward a conserved transcription program for the stem cell state. © 2014 AlphaMed Press.

  19. Capacity Payments in Restructured Markets under Low and High Penetration Levels of Renewable Energy

    Energy Technology Data Exchange (ETDEWEB)

    Jenkin, Thomas [National Renewable Energy Lab. (NREL), Golden, CO (United States); Beiter, Philipp [National Renewable Energy Lab. (NREL), Golden, CO (United States); Margolis, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-02-11

    remain in implementing capacity markets that provide both adequate operational and investment incentives, particularly under high-VRE scenarios with greater need for flexible capacity.

  20. Transparent hydrogel with enhanced water retention capacity by introducing highly hydratable salt

    OpenAIRE

    Bai, Yuanyuan; Chen, Baohong; Xiang, Feng; Zhou, Jinxiong; Wang, Hong; Suo, Zhigang

    2014-01-01

    Polyacrylamide hydrogels containing salt as electrolyte have been used as highly stretchable transparent electrodes in flexible electronics, but those hydrogels are easy to dry out due to water evaporation. Targeted, we try to enhance water retention capacity of polyacrylamide hydrogel by introducing highly hydratable salts into the hydrogel. These hydrogels show enhanced water retention capacity in different level. Specially, polyacrylamide hydrogel containing high content of lithium chlorid...

  1. Transparent hydrogel with enhanced water retention capacity by introducing highly hydratable salt

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Yuanyuan; Xiang, Feng; Wang, Hong, E-mail: hwang@mail.xjtu.edu.cn, E-mail: suo@seas.harvard.edu [Electronic Materials Research Laboratory, School of Electronics and Information Engineering, Xi' an Jiaotong University, Xi' an 710049 (China); Chen, Baohong; Zhou, Jinxiong [State Key Laboratory for Strength and Vibration of Mechanical Structures, International Center for Applied Mechanics and School of Aerospace, Xi' an Jiaotong University, Xi' an 710049 (China); Suo, Zhigang, E-mail: hwang@mail.xjtu.edu.cn, E-mail: suo@seas.harvard.edu [School of Engineering and Applied Sciences, Kavli Institute of Bionano Science and Technology, Harvard University, Cambridge, Massachusetts 02138 (United States)

    2014-10-13

    Polyacrylamide hydrogels containing salt as electrolyte have been used as highly stretchable transparent electrodes in flexible electronics, but those hydrogels are easy to dry out due to water evaporation. Targeted, we try to enhance water retention capacity of polyacrylamide hydrogel by introducing highly hydratable salts into the hydrogel. These hydrogels show enhanced water retention capacity in different level. Specially, polyacrylamide hydrogel containing high content of lithium chloride can retain over 70% of its initial water even in environment with relative humidity of only 10% RH. The excellent water retention capacities of these hydrogels will make more applications of hydrogels become possible.

  2. Transparent hydrogel with enhanced water retention capacity by introducing highly hydratable salt

    International Nuclear Information System (INIS)

    Bai, Yuanyuan; Xiang, Feng; Wang, Hong; Chen, Baohong; Zhou, Jinxiong; Suo, Zhigang

    2014-01-01

    Polyacrylamide hydrogels containing salt as electrolyte have been used as highly stretchable transparent electrodes in flexible electronics, but those hydrogels are easy to dry out due to water evaporation. Targeted, we try to enhance water retention capacity of polyacrylamide hydrogel by introducing highly hydratable salts into the hydrogel. These hydrogels show enhanced water retention capacity in different level. Specially, polyacrylamide hydrogel containing high content of lithium chloride can retain over 70% of its initial water even in environment with relative humidity of only 10% RH. The excellent water retention capacities of these hydrogels will make more applications of hydrogels become possible.

  3. Mechanics of high-capacity electrodes in lithium-ion batteries

    International Nuclear Information System (INIS)

    Zhu, Ting

    2016-01-01

    Rechargeable batteries, such as lithium-ion batteries, play an important role in the emerging sustainable energy landscape. Mechanical degradation and resulting capacity fade in high-capacity electrode materials critically hinder their use in high-performance lithium-ion batteries. This paper presents an overview of recent advances in understanding the electrochemically-induced mechanical behavior of the electrode materials in lithium-ion batteries. Particular emphasis is placed on stress generation and facture in high-capacity anode materials such as silicon. Finally, we identify several important unresolved issues for future research. (topical review)

  4. A large capacity, high-speed multiparameter multichannel analysis system

    International Nuclear Information System (INIS)

    Hendricks, R.W.; Suehiro, S.; Seeger, P.A.; Scheer, J.W.

    1982-01-01

    A data acquisition system for recording multiparameter digital data into a large memory array at over 2.5 MHz is described. The system consists of a MOSTEK MK 8600 2048 K x 24-bit memory system, I/O ports to various external devices including the CAMAC dataway, a memory incrementer/adder and a daisy-chain of experiment-specific modules which calculate the memory address which is to be incremented. The design of the daisy-chain permits multiple modules and provides for easy modification as experimental needs change. The system has been designed for use in multiparameter, multichannel analysis of high-speed data gathered by position-sensitive detectors at conventional and synchrotron X-ray sources as well as for fixed energy and time-of-flight diffraction at continuous and pulsed neutron sources. Modules which have been developed to date include a buffer for two-dimensional position-sensitive detectors, a mapper for high-speed coordinate transformations, a buffered time-of-flight clock, a time-correlator for synchronized diffraction experiments, and a display unit for data bus diagnostics. (orig.)

  5. Edge-riched graphene nanoribbon for high capacity electrode materials

    International Nuclear Information System (INIS)

    Ping, Yunjie; Zhang, Yupeng; Gong, Youning; Cao, Bing; Fu, Qiang; Pan, Chunxu

    2017-01-01

    Highlights: •The graphene nanoribbon has been successfully synthesized by longitudinal unzipping of carbon nanotubes with oxidants KMnO 4 . •Compared with graphene oxide and carbon nanotubes, graphene nanoribbon shows the largest capacitance up to ∼202F/g at a scan rate of 5 mV/s. •The importance of the location of functional groups and the importance of the edge structure. •The pseudo-capacitance material should have high electron transfer and rapid ion diffusion. -- Abstract: Carbon materials have attracted great attention for their diversified applications in supercapacitors, and different structures of carbon have been reported to exhibit dissimilar electrochemical properties. In the past, activated carbons, carbon nanotubes (CNTs), carbon nanofibers and graphene have been shown to have excellent electrochemical performances, but it still remains a problem on how to improve the capacitance of carbon-based materials effectively from the viewpoint of their giant commercial potential. Noticing that connecting chemical groups to carbon can provide large pseudo-capacitance, we hereby demonstrated that the position of the chemical groups also plays an important role in the pseudo-capacitance. In our work, we synthesized graphene nanoribbon (GNR), graphene oxide (GO) and functional MWCNTs and showed that GNR has larger capacitance (calculated to be 202 F/g at a scan rate of 5 mV/s) and energy density compared to CNTs and GO when using as electrode materials. Furthermore, the supercapacitor device based on as-synthesized GNR exhibits excellent cycle stability and rate capability which evident is potential in high performance supercapacitor. Revealing the source of the capacitance, we found that though GNR has less oxygen-containing groups, it has larger pseudo-capacitance than GO and CNTs due to the remarkable edge-riched structure with high activity in electrochemical reactions. This finding highlights the importance of edge structure in carbon-based pseudo

  6. Novel peptide ligand with high binding capacity for antibody purification

    DEFF Research Database (Denmark)

    Lund, L. N.; Gustavsson, P. E.; Michael, R.

    2012-01-01

    Small synthetic ligands for protein purification have become increasingly interesting with the growing need for cheap chromatographic materials for protein purification and especially for the purification of monoclonal antibodies (mAbs). Today, Protein A-based chromatographic resins are the most...... commonly used capture step in mAb down stream processing; however, the use of Protein A chromatography is less attractive due to toxic ligand leakage as well as high cost. Whether used as an alternative to the Protein A chromatographic media or as a subsequent polishing step, small synthetic peptide...... ligands have an advantage over biological ligands; they are cheaper to produce, ligand leakage by enzymatic degradation is either eliminated or significantly reduced, and they can in general better withstand cleaning in place (CIP) conditions such as 0.1 M NaOH. Here, we present a novel synthetic peptide...

  7. Large capacity, high-speed multiparameter multichannel analysis system

    International Nuclear Information System (INIS)

    Hendricks, R.W.; Seeger, P.A.; Scheer, J.W.; Suehiro, S.

    1980-01-01

    A data acquisition system for recording multiparameter digital data into a large memory array at over 2.5 MHz is described. The system consists of a MOSTEK MK8600 2048K x 24-bit memory system, I/O ports to various external devices including the CAMAC dataway, a memory incrementer/adder and a daisy-chain of experiment-specific modules which calculate the memory address which is to be incremented. The design of the daisy-chain permits multiple modules and provides for easy modification as experimental needs change. The system has been designed for use in multiparameter, multichannel analysis of high-speed data gathered by position-sensitive detectors at conventional and synchrotron x-ray sources as well as for fixed energy and time-of-flight diffraction at continuous and pulsed neutron sources

  8. A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity.

    Directory of Open Access Journals (Sweden)

    Romain Cartoni

    Full Text Available Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons. Here, using a microfluidic culture system we compared neurons co-deleted for PTEN and SOCS3, an established model of high axonal regeneration capacity, to control neurons. We measured the axonal transport of three cargos (mitochondria, synaptic vesicles and late endosomes in regenerating axons and found that the transport of mitochondria, but not the other cargos, was increased in PTEN/SOCS3 co-deleted axons relative to controls. The results reported here suggest a pivotal role for this organelle during axonal regeneration.

  9. Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma*

    Science.gov (United States)

    Bourguignon, Lilly Y. W.; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-01-01

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  10. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.

    Science.gov (United States)

    Bourguignon, Lilly Y W; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-09-21

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  11. Systems-level computational modeling demonstrates fuel selection switching in high capacity running and low capacity running rats

    Science.gov (United States)

    Qi, Nathan R.

    2018-01-01

    High capacity and low capacity running rats, HCR and LCR respectively, have been bred to represent two extremes of running endurance and have recently demonstrated disparities in fuel usage during transient aerobic exercise. HCR rats can maintain fatty acid (FA) utilization throughout the course of transient aerobic exercise whereas LCR rats rely predominantly on glucose utilization. We hypothesized that the difference between HCR and LCR fuel utilization could be explained by a difference in mitochondrial density. To test this hypothesis and to investigate mechanisms of fuel selection, we used a constraint-based kinetic analysis of whole-body metabolism to analyze transient exercise data from these rats. Our model analysis used a thermodynamically constrained kinetic framework that accounts for glycolysis, the TCA cycle, and mitochondrial FA transport and oxidation. The model can effectively match the observed relative rates of oxidation of glucose versus FA, as a function of ATP demand. In searching for the minimal differences required to explain metabolic function in HCR versus LCR rats, it was determined that the whole-body metabolic phenotype of LCR, compared to the HCR, could be explained by a ~50% reduction in total mitochondrial activity with an additional 5-fold reduction in mitochondrial FA transport activity. Finally, we postulate that over sustained periods of exercise that LCR can partly overcome the initial deficit in FA catabolic activity by upregulating FA transport and/or oxidation processes. PMID:29474500

  12. Photonics applications in high-capacity data link terminals

    Science.gov (United States)

    Shi, Zan; Foshee, James J.

    2001-12-01

    Radio systems and, in particular, RF data link systems are evolving toward progressively more bandwidth and higher data rates. For many military RF data link applications the data transfer requirements exceed one Gigabit per second. Airborne collectors need to transfer sensor information and other large data files to ground locations and other airborne terminals, including the rel time transfer of files. It is a challenge to the system designer to provide a system design, which meets the RF link budget requirements for a one Gigabit per second data link; and there is a corresponding challenge in the development of the terminal architecture and hardware. The utilization of photonic circuitry and devices as a part of the terminal design offers the designer some alternatives to the conventional RF hardware design within the radio. Areas of consideration for the implementation of photonic technology include Gigabit per second baseband data interfaces with fiber along with the associated clocking rates and extending these Gigabit data rates into the radio for optical processing technology; optical interconnections within the individual circuit boards in the radio; and optical backplanes to allow the transfer of not only the Gigabit per second data rates and high speed clocks but other RF signals within the radio. True time delay using photonics in phased array antennas has been demonstrated and is an alternative to the conventional phase shifter designs used in phased array antennas, and remoting of phased array antennas from the terminal electronics in the Ku and Ka frequency bands using fiber optics as the carrier to minimize the RF losses, negate the use of the conventional waveguides, and allow the terminal equipment to be located with other electronic equipment in the aircraft suitable for controlled environment, ready access, and maintenance. The various photonics design alternatives will be discussed including specific photonic design approaches. Packaging

  13. Final report: High current capacity high temperature superconducting film based tape for high field magnets

    International Nuclear Information System (INIS)

    Ying Xin

    2000-01-01

    The primary goal of the program was to establish the process parameters for the continuous deposition of high quality, superconducting YBCO films on one meter lengths of buffered RABiTS tape using MOCVD and to characterize the potential utility of the resulting tapes in high field magnet applications

  14. Ultra-High Capacity Silicon Photonic Interconnects through Spatial Multiplexing

    Science.gov (United States)

    Chen, Christine P.

    -fabrication. Through ModePROP simulations, optimizing device performance dynamically post-fabrication is analyzed, through either electro-optical or thermo-optical means. By biasing the arm introducing the slight spectral offset, we can quantifiably improve device performance. Scaling bandwidth is experimentally demonstrated through the device at 3 modes, 2 wavelengths, and 40 Gb/s data rate for 240 Gb/s aggregate bandwidth, with the potential to reduce power penalty per the device optimization process we described. A main motivation for this on-chip spatial multiplexing is the need to reduce costs. As the laser source serves as the greatest power consumer in an optical system, mode-division multiplexing and other forms of spatial multiplexing can be implemented to push its potentially prohibitive cost metrics down. In order to demonstrate an intelligent platform capable of dynamically multicasting data and reallocating power as needed by the system, we must first initialize the switch fabric to control with an electronic interface. A dithering mechanism, whereby exact cross, bar, and sub-percentage states are enforced through the device, is described here. Such a method could be employed for actuating the device table of bias values to states automatically. We then employ a dynamic power reallocation algorithm through a data acquisition unit, showing real-time channel recovery for channels experiencing power loss by diverting power from paths that could tolerate it. The data that is being multicast through the system is experimentally shown to be error-free at 40 Gb/s data rate, when transmitting from one to three clients and going from automatic bar/cross states to equalized power distribution. For the last portion of this topic, the switch fabric was inserted into a high-performance computing system. In order to run benchmarks at 10 Gb/s data ontop of the switch fabric, a newer model of the control plane was implemented to toggle states according to the command issued by the server

  15. ERK inhibition promotes neuroectodermal precursor commitment by blocking self-renewal and primitive streak formation of the epiblast.

    Science.gov (United States)

    Yu, Yang; Wang, Xiaoxiao; Zhang, Xiaoxin; Zhai, Yanhua; Lu, Xukun; Ma, Haixia; Zhu, Kai; Zhao, Tongbiao; Jiao, Jianwei; Zhao, Zhen-Ao; Li, Lei

    2018-01-05

    Pluripotent stem cells hold great promise for regenerative medicine. However, before clinical application, reproducible protocols for pluripotent stem cell differentiation should be established. Extracellular signal-regulated protein kinase (ERK) signaling plays a central role for the self-renewal of epiblast stem cells (EpiSCs), but its role for subsequent germ layer differentiation is still ambiguous. We proposed that ERK could modulate differentiation of the epiblast. PD0325901 was used to inhibit ERK activation during the differentiation of embryonic stem cells and EpiSCs. Immunofluorescence, western blot analysis, real-time PCR and flow cytometry were used to detect germ layer markers and pathway activation. We demonstrate that the ERK phosphorylation level is lower in neuroectoderm of mouse E7.5 embryos than that in the primitive streak. ERK inhibition results in neural lineage commitment of epiblast. Mechanistically, PD0325901 abrogates the expression of primitive streak markers by β-catenin retention in the cytoplasm, and inhibits the expression of OCT4 and NANOG during EpiSC differentiation. Thus, EpiSCs differentiate into neuroectodermal lineage efficiently under PD0325901 treatment. These results suggest that neuroectoderm differentiation does not require extrinsic signals, supporting the default differentiation of neural lineage. We report that a single ERK inhibitor, PD0325901, can specify epiblasts and EpiSCs into neural-like cells, providing an efficient strategy for neural differentiation.

  16. Histone Methylation and microRNA-dependent Regulation of Epigenetic Activities in Neural Progenitor Self-Renewal and Differentiation.

    Science.gov (United States)

    Cacci, Emanuele; Negri, Rodolfo; Biagioni, Stefano; Lupo, Giuseppe

    2017-01-01

    Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages.

  17. Single-Cell Analyses of ESCs Reveal Alternative Pluripotent Cell States and Molecular Mechanisms that Control Self-Renewal

    Directory of Open Access Journals (Sweden)

    Dmitri Papatsenko

    2015-08-01

    Full Text Available Analyses of gene expression in single mouse embryonic stem cells (mESCs cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM. In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.

  18. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation.

    Science.gov (United States)

    Di Tullio, Alessandro; Passaro, Diana; Rouault-Pierre, Kevin; Purewal, Sukhveer; Bonnet, Dominique

    2017-07-11

    Nuclear factor erythroid-derived 2 (NF-E2) has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs) not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG) mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated) and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling.

    Science.gov (United States)

    He, Xi C; Zhang, Jiwang; Tong, Wei-Gang; Tawfik, Ossama; Ross, Jason; Scoville, David H; Tian, Qiang; Zeng, Xin; He, Xi; Wiedemann, Leanne M; Mishina, Yuji; Li, Linheng

    2004-10-01

    In humans, mutations in BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden disease, respectively. The development of polyposis is a common feature of these diseases, suggesting that there is an association between BMP and PTEN pathways. The mechanistic link between BMP and PTEN pathways and the related etiology of juvenile polyposis is unresolved. Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome. We show that BMP signaling suppresses Wnt signaling to ensure a balanced control of stem cell self-renewal. Mechanistically, PTEN, through phosphatidylinosital-3 kinase-Akt, mediates the convergence of the BMP and Wnt pathways on control of beta-catenin. Thus, BMP signaling may control the duplication of intestinal stem cells, thereby preventing crypt fission and the subsequent increase in crypt number.

  20. Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor

    Directory of Open Access Journals (Sweden)

    Ebrahim Shahbazi

    2016-04-01

    Full Text Available Direct conversion of somatic cells into neural stem cells (NSCs by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. In addition, the single-seeded induced NSCs were able to form NSC colonies with efficiency comparable with control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating, and attaining neural phenotypes after transplantation into neonatal mouse and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts.

  1. Identification of CHD1L as an Important Regulator for Spermatogonial Stem Cell Survival and Self-Renewal

    Directory of Open Access Journals (Sweden)

    Shan-Shan Liu

    2016-01-01

    Full Text Available Chromodomain helicase/ATPase DNA binding protein 1-like gene (Chd1l participates in chromatin-dependent processes, including transcriptional activation and DNA repair. In this study, we have found for the first time that Chd1l is mainly expressed in the testicular tissues of prepubertal and adult mice and colocalized with PLZF, OCT4, and GFRα1 in the neonatal mouse testis and THY1+ undifferentiated spermatogonia or spermatogonial stem cells (SSCs. Knockdown of endogenous Chd1l in cultured mouse undifferentiated SSCs inhibited the expression levels of Oct4, Plzf, Gfrα1, and Pcna genes, suppressed SSC colony formation, and reduced BrdU incorporation, while increasing SSC apoptosis. Moreover, the Chd1l gene expression is activated by GDNF in the cultured mouse SSCs, and the GDNF signaling pathway was modulated by endogenous levels of Chd1l; as demonstrated by the gene expression levels of GDNF, inducible transcripts Etv5, Bcl6b, Pou3f, and Lhx1, but not that of GDNF-independent gene, Taf4b, were significantly downregulated by Chd1l knockdown in mouse SSCs. Taken together, this study provides the first evidence to support the notion that Chd1l is an intrinsic and novel regulator for SSC survival and self-renewal, and it exerts such regulation at least partially through a GDNF signaling pathway.

  2. DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.

    Science.gov (United States)

    Fütterer, Agnes; de Celis, Jésus; Navajas, Rosana; Almonacid, Luis; Gutiérrez, Julio; Talavera-Gutiérrez, Amaia; Pacios-Bras, Cristina; Bernascone, Ilenia; Martin-Belmonte, Fernando; Martinéz-A, Carlos

    2017-04-11

    Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. We show that embryonic stem cells (ESCs) mainly express DIDO3 and that their differentiation after leukemia inhibitory factor withdrawal requires DIDO1 expression. C-terminal truncation of DIDO3 (Dido3ΔCT) impedes ESC differentiation while retaining self-renewal; small hairpin RNA-Dido1 ESCs have the same phenotype. Dido3ΔCT ESC differentiation is rescued by ectopic expression of DIDO3, which binds the Dido locus via H3K4me3 and RNA POL II and induces DIDO1 expression. DIDO1, which is exported to cytoplasm, associates with, and is N-terminally phosphorylated by PKCiota. It binds the E3 ubiquitin ligase WWP2, which contributes to cell fate by OCT4 degradation, to allow expression of primitive endoderm (PE) markers. PE formation also depends on phosphorylated DIDO3 localization to centrosomes, which ensures their correct positioning for PE cell polarization. We propose that DIDO isoforms act as a switchboard that regulates genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.

    Science.gov (United States)

    Liu, Shuo; Zhang, Cun; Zhang, Kuo; Gao, Yuan; Wang, Zhaowei; Li, Xiaoju; Cheng, Guang; Wang, Shuning; Xue, Xiaochang; Li, Weina; Zhang, Wei; Zhang, Yingqi; Xing, Xianghui; Li, Meng; Hao, Qiang

    2017-07-04

    Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

  4. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation

    Directory of Open Access Journals (Sweden)

    Alessandro Di Tullio

    2017-07-01

    Full Text Available Nuclear factor erythroid-derived 2 (NF-E2 has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation.

  5. The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53.

    Science.gov (United States)

    Flamini, Valentina; Ghadiali, Rachel S; Antczak, Philipp; Rothwell, Amy; Turnbull, Jeremy E; Pisconti, Addolorata

    2018-03-13

    Satellite cells are adult muscle stem cells residing in a specialized niche that regulates their homeostasis. How niche-generated signals integrate to regulate gene expression in satellite cell-derived myoblasts is poorly understood. We undertook an unbiased approach to study the effect of the satellite cell niche on satellite cell-derived myoblast transcriptional regulation and identified the tumor suppressor p53 as a key player in the regulation of myoblast quiescence. After activation and proliferation, a subpopulation of myoblasts cultured in the presence of the niche upregulates p53 and fails to differentiate. When satellite cell self-renewal is modeled ex vivo in a reserve cell assay, myoblasts treated with Nutlin-3, which increases p53 levels in the cell, fail to differentiate and instead become quiescent. Since both these Nutlin-3 effects are rescued by small interfering RNA-mediated p53 knockdown, we conclude that a tight control of p53 levels in myoblasts regulates the balance between differentiation and return to quiescence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. High-capacity, high-strength trailer designs for the GA-4/GA-9 casks

    International Nuclear Information System (INIS)

    Rickard, N.D.; Kissinger, J.A.; Taylor, C.; Zimmer, A.

    1991-01-01

    General Atomics (GA) is developing final designs for two dedicated legal-weight trailers to transport the GA-4 and GA-9 Spent-Fuel Casks. The basic designs for these high-capacity, high-strength trailers are essentially identical except for small modifications to account for the differences in cask geometry. The authors are designing both trailers to carry a 55,000 lb (24,900 kg) payload and to withstand a 2.5 g vertical design load. The GA-4 and GA-9 trailers are designed for significantly higher loads than are typical commercial semitrailers, which are designed to loads in the range of 1.7 to 2.0 g. To meet the federal gross vehicle weight limit for legal-weight trucks, GA has set a target design weight for the trailers of 9000 lb (4080 kg). This weight includes the personnel barrier, cask tiedowns, and impact limiter removal and storage system. Based on the preliminary trailer designs, the final design weight will to be very close to this target weight

  7. High-capacity, high-strength trailer designs for the GA-4/GA-9 Casks

    International Nuclear Information System (INIS)

    Kissinger, J.A.; Rickard, N.D.; Taylor, C.; Zimmer, A.

    1991-01-01

    General Atomics (GA) is developing final designs for two dedicated legal-weight trailers to transport the GA-4 and GA-9 Spent-Fuel Casks. The basic designs for these high-capacity, high-strength trailers are essentially identical except for small modifications to account for the differences in cask geometry. We are designing both trailers to carry a 55,000 lb (24,900 kg) payload and to withstand a 2.5 g vertical design load. The GA-4 and GA-9 trailers are designed for significantly higher loads than are typical commercial semitrailers, which are designed to loads in the range of 1.7 to 2.0 g. To meet the federal gross vehicle weight limit for legal-weight trucks, GA has set a target design weight for the trailers of 9000 lb (4080 kg). This weight includes the personnel barrier, cask tiedowns, and impact limiter removal and storage system. Based on the preliminary trailer designs, the final design weight is expected to be very close to this target weight. 3 refs., 3 figs

  8. Recycling potential for low voltage and high voltage high rupturing capacity fuse links.

    Science.gov (United States)

    Psomopoulos, Constantinos S; Barkas, Dimitrios A; Kaminaris, Stavros D; Ioannidis, George C; Karagiannopoulos, Panagiotis

    2017-12-01

    Low voltage and high voltage high-rupturing-capacity fuse links are used in LV and HV installations respectively, protecting mainly the LV and HV electricity distribution and transportation networks. The Waste Electrical and Electronic Equipment Directive (2002/96/EC) for "Waste of electrical and electronic equipment" is the main related legislation and as it concerns electrical and electronic equipment, it includes electric fuses. Although, the fuse links consist of recyclable materials, only small scale actions have been implemented for their recycling around Europe. This work presents the possibilities for material recovery from this specialized industrial waste for which there are only limited volume data. Furthermore, in order to present the huge possibilities and environmental benefits, it presents the potential for recycling of HRC fuses used by the Public Power Corporation of Greece, which is the major consumer for the country, but one of the smallest ones in Europe and globally, emphasizing in this way in the issue. According to the obtained results, fuse recycling could contribute to the effort for minimize the impacts on the environment through materials recovery and reduction of the wastes' volume disposed of in landfills. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. High energy bursts from a solid state laser operated in the heat capacity limited regime

    Science.gov (United States)

    Albrecht, G.; George, E.V.; Krupke, W.F.; Sooy, W.; Sutton, S.B.

    1996-06-11

    High energy bursts are produced from a solid state laser operated in a heat capacity limited regime. Instead of cooling the laser, the active medium is thermally well isolated. As a result, the active medium will heat up until it reaches some maximum acceptable temperature. The waste heat is stored in the active medium itself. Therefore, the amount of energy the laser can put out during operation is proportional to its mass, the heat capacity of the active medium, and the temperature difference over which it is being operated. The high energy burst capacity of a heat capacity operated solid state laser, together with the absence of a heavy, power consuming steady state cooling system for the active medium, will make a variety of applications possible. Alternately, cooling takes place during a separate sequence when the laser is not operating. Industrial applications include new material working processes. 5 figs.

  10. The Effects of High Intensity Interval Training vs Steady State Training on Aerobic and Anaerobic Capacity

    OpenAIRE

    Carl Foster, Courtney V. Farland, Flavia Guidotti, Michelle Harbin, Brianna Roberts, Jeff Schuette, Andrew Tuuri, Scott T. Doberstein, John P. Porcari

    2015-01-01

    High intensity interval training (HIIT) has become an increasingly popular form of exercise due to its potentially large effects on exercise capacity and small time requirement. This study compared the effects of two HIIT protocols vs steady-state training on aerobic and anaerobic capacity following 8-weeks of training. Fifty-five untrained college-aged subjects were randomly assigned to three training groups (3x weekly). Steady-state (n = 19) exercised (cycle ergometer) 20 minutes at 90% of ...

  11. The Decline of Soil Infiltration Capacity Due To High Elevation Groundwater

    OpenAIRE

    Isri Ronald Mangangka

    2008-01-01

    Infiltration capacity of soil mainly depends on two factors; the particle size and the moisture content of the soil. Groundwater increases the soil moisture, not only below the water table but also within the capillary zone, above the water table. Field experiment in a high groundwater area was conducted to understand the relationship among the groundwater, soil moisture and infiltration capacity. Using a single ring infiltrometer, the effect of groundwater in the infiltration rate was observ...

  12. Preparation and characterization of magnetic polymer nanospheres with high protein binding capacity

    International Nuclear Information System (INIS)

    Liu Xianqiao; Guan Yueping; Liu Huizhou; Ma Zhiya; Yang Yu; Wu Xiaobing

    2005-01-01

    A novel magnetic support with high protein binding capacity was prepared by mini-emulsion polymerization. The magnetic poly(methacrylate-divinylbenzene) nanospheres prepared are 390 nm in diameter with narrow size distribution and star-like external morphology which leads to a large increase in specific surface area. Experimental results indicate that the maximum protein binding capacity is 316 mg bovine hemoglobin (BHb)/g support

  13. Wnt/β-catenin and LIF-Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal.

    Science.gov (United States)

    Ye, Shoudong; Zhang, Dongming; Cheng, Fei; Wilson, Daniel; Mackay, Jeffrey; He, Kan; Ban, Qian; Lv, Feng; Huang, Saifei; Liu, Dahai; Ying, Qi-Long

    2016-01-15

    Activation of leukemia inhibitor factor (LIF)-Stat3 or Wnt/β-catenin signaling promotes mouse embryonic stem cell (mESC) self-renewal. A myriad of downstream targets have been identified in the individual signal pathways, but their common targets remain largely elusive. In this study, we found that the LIF-Stat3 and Wnt/β-catenin signaling pathways converge on Sp5 to promote mESC self-renewal. Forced Sp5 expression can reproduce partial effects of Wnt/β-catenin signaling but mimics most features of LIF-Stat3 signaling to maintain undifferentiated mESCs. Moreover, Sp5 is able to convert mouse epiblast stem cells into a naïve pluripotent state. Thus, Sp5 is an important component of the regulatory network governing mESC naïve pluripotency. © 2016. Published by The Company of Biologists Ltd.

  14. Effects of high fluoride intake on child mental work capacity: preliminary investigation into the mechanisms involved

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.; Li, X.J.; Wei, S.Q. [Child & Adolescent Hygiene Teaching Research Station, Chengdu (China)

    2008-10-15

    A study was carried out on 157 children, age 12-13, from a coal-burning fluorosis endemic area together with an experiment looking into the effect of high fluoride intake in animals. The results showed that early, prolonged high fluoride intake causes a decrease in a child's mental work capacity and that prolonged high uptake of fluoride causes a child's levels of hair zinc to drop. A multifactoral correlative analysis demonstrated a direct correlation between hair zinc and mental work capacity. The decrease of 5-hydroxyindoleacetic acid and the increase of norepinephrine in animal brains exposed to high levels of fluoride suggest a possible mechanism for mental work capacity deficits in children. However, further research is necessary.

  15. Generation Capacity Investments and High Levels of Renewables. The Impact of a German Capacity Market on Northwest Europe. Discussion paper

    Energy Technology Data Exchange (ETDEWEB)

    Ozdemir, O.; De Joode, J.; Koutstaal, P.R.; Van Hout, M. [ECN Policy Studies, Amsterdam (Netherlands)

    2013-05-15

    Presently, Northwest European centralised electricity markets are designed as 'energy-only' markets. In an energy-only market, the price received for electricity produced is set by the marginal generation unit. Potentially, the designs of these markets could leave the owners of these units with 'missing money': i.e. money that is required to recover investment cost. Further, increasing penetration of renewables could exacerbate this problem. Of all the different options available to tackle the 'missing money' problem, capacity mechanisms have attracted most of the attention in recent policy debates in Europe. This paper contributes to ongoing policy discussions by providing a quantitative analysis of the phenomena of 'missing money' and capacity mechanisms in Northwest Europe. Our analysis shows that in the case of energy-only markets with a much higher penetration of intermittent electricity sources such as wind and solar PV, the 'missing money' problem may be aggravated, because operating hours for peak and mid-merit order capacity will be considerably reduced. Furthermore, unilateral introduction of capacity mechanisms in integrated electricity markets can have considerable impacts on cross-border electricity flows and investment decisions. Stand-alone introduction of a capacity market in Germany will likely result in higher investments in Germany at the expense of lower investments outside Germany and an increase in net exports from Germany. A possible advantage of a unilateral capacity mechanism in Germany may be a reduction in super-peak prices in the larger market area. Thus, neighbouring countries may have the possibility to free ride on the increase in flexible capacity in Germany. However, this advantage is conditional and depends on sufficient availability of interconnection capacity necessary to be able to use this reserve capacity. Otherwise, security of supply might be more at risk if the German

  16. Heat capacity of iron, aluminum, and chromium vanadates at high temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Cheshnitskii, S.M.; Fotiev, A.A.; Ignashin, V.P.; Kesler, Y.A.

    1985-09-01

    The thermodynamic characteristics of compounds participating in the processing of vanadium-containing raw materials have not been sufficiently investigated. In this paper the authors report on measurements of the heat capacities of the compounds FeVO/sub 4/, CrVO/sub 4/, AIVO/sub 4/, Fe/sub 2/V/sub 4/O/sub 13/ and FeCr(VO/sub 4/)/sub 2/ at high temperatures. The obtained experimental data on the high-temperature heat capacity of iron, aluminum, and chromium vanadates makes it possible to calculate the thermodynamic functions of these compounds at high temperatures.

  17. Mitochondrial activity in the regulation of stem cell self-renewal and differentiation.

    Science.gov (United States)

    Khacho, Mireille; Slack, Ruth S

    2017-12-01

    Mitochondria are classically known as the essential energy producers in cells. As such, the activation of mitochondrial metabolism upon cellular differentiation was deemed a necessity to fuel the high metabolic needs of differentiated cells. However, recent studies have revealed a direct role for mitochondrial activity in the regulation of stem cell fate and differentiation. Several components of mitochondrial metabolism and respiration have now been shown to regulate different aspects of stem cell differentiation through signaling, transcriptional, proteomic and epigenetic modulations. In light of these findings mitochondrial metabolism is no longer considered a consequence of cellular differentiation, but rather a key regulatory mechanism of this process. This review will focus on recent progress that defines mitochondria as the epicenters for the regulation of stem cell fate decisions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Lhx2 expression promotes self-renewal of a distinct multipotential hematopoietic progenitor cell in embryonic stem cell-derived embryoid bodies.

    Directory of Open Access Journals (Sweden)

    Lina Dahl

    Full Text Available The molecular mechanisms regulating the expansion of the hematopoietic system including hematopoietic stem cells (HSCs in the fetal liver during embryonic development are largely unknown. The LIM-homeobox gene Lhx2 is a candidate regulator of fetal hematopoiesis since it is expressed in the fetal liver and Lhx2(-/- mice die in utero due to severe anemia. Moreover, expression of Lhx2 in embryonic stem (ES cell-derived embryoid bodies (EBs can lead to the generation of HSC-like cell lines. To further define the role of this transcription factor in hematopoietic regulation, we generated ES cell lines that enabled tet-inducible expression of Lhx2. Using this approach we observed that Lhx2 expression synergises with specific signalling pathways, resulting in increased frequency of colony forming cells in developing EB cells. The increase in growth factor-responsive progenitor cells directly correlates to the efficiency in generating HSC-like cell lines, suggesting that Lhx2 expression induce self-renewal of a distinct multipotential hematopoietic progenitor cell in EBs. Signalling via the c-kit tyrosine kinase receptor and the gp130 signal transducer by IL-6 is necessary and sufficient for the Lhx2 induced self-renewal. While inducing self-renewal of multipotential progenitor cells, expression of Lhx2 inhibited proliferation of primitive erythroid precursor cells and interfered with early ES cell commitment, indicating striking lineage specificity of this effect.

  19. Completion of a high efficiency ultralarge capacity three-phase transformer

    International Nuclear Information System (INIS)

    Maejima, Masaaki; Maruyama, Katsuya; Fukuda, Teruo.

    1986-01-01

    As for the boosting transformers for thermal and nuclear power stations, at present the ultralarge capacity transformers of 1000 - 1200 MVA class are the main, and particularly in nuclear power, accompanying the development of improved type BWRs and the rise of system stability, there is the tendency toward further large capacity and large size. Consequently, reflecting the recent rise of energy cost, the demand of energy conservation and the reduction of required sites heightened largely as well as the high reliability. In order to meet these demands, Hitachi Ltd. has established the technology of changing to iron machines such as ultralarge iron cores and ultralarge capacity undivided disk windings using the latest design and manufacture techniques were applied to the 525 kV, 1200 MVA transformer for No.4 plant in Fukushima No.2 Nuclear Power Station, Tokyo Electric Power Co., Inc., thus a three-phase transformer of the highest level, high efficiency and ultralarge capacity was completed. In this paper, the outline of this transformer and the test for verifying its reliability are described. The technical change of large capacity three-phase transformers, the specifications, construction, manufacture, reliability test and the effect of modification of this transformer, and the expansion of application to the next generation ultralarge capacity transformers are reported. (Kako, I.)

  20. A biomimetic high-capacity phenazine-based anolyte for aqueous organic redox flow batteries

    Science.gov (United States)

    Hollas, Aaron; Wei, Xiaoliang; Murugesan, Vijayakumar; Nie, Zimin; Li, Bin; Reed, David; Liu, Jun; Sprenkle, Vincent; Wang, Wei

    2018-06-01

    Aqueous soluble organic (ASO) redox-active materials have recently attracted significant attention as alternatives to traditional transition metal ions in redox flow batteries (RFB). However, reported reversible capacities of ASO are often substantially lower than their theoretical values based on the reported maximum solubilities. Here, we describe a phenazine-based ASO compound with an exceptionally high reversible capacity that exceeds 90% of its theoretical value. By strategically modifying the phenazine molecular structure, we demonstrate an increased solubility from near-zero with pristine phenazine to as much as 1.8 M while also shifting its redox potential by more than 400 mV. An RFB based on a phenazine derivative (7,8-dihydroxyphenazine-2-sulfonic acid) at its near-saturation concentration exhibits an operating voltage of 1.4 V with a reversible anolyte capacity of 67 Ah l-1 and a capacity retention of 99.98% per cycle over 500 cycles.

  1. Improved Performance and Safety for High Energy Batteries Through Use of Hazard Anticipation and Capacity Prediction

    Science.gov (United States)

    Atwater, Terrill

    1993-01-01

    Prediction of the capacity remaining in used high rate, high energy batteries is important information to the user. Knowledge of the capacity remaining in used batteries results in better utilization. This translates into improved readiness and cost savings due to complete, efficient use. High rate batteries, due to their chemical nature, are highly sensitive to misuse (i.e., over discharge or very high rate discharge). Battery failure due to misuse or manufacturing defects could be disastrous. Since high rate, high energy batteries are expensive and energetic, a reliable method of predicting both failures and remaining energy has been actively sought. Due to concerns over safety, the behavior of lithium/sulphur dioxide cells at different temperatures and current drains was examined. The main thrust of this effort was to determine failure conditions for incorporation in hazard anticipation circuitry. In addition, capacity prediction formulas have been developed from test data. A process that performs continuous, real-time hazard anticipation and capacity prediction was developed. The introduction of this process into microchip technology will enable the production of reliable, safe, and efficient high energy batteries.

  2. Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages

    Science.gov (United States)

    Waqas, Syed F. Hassnain; Hoang, Anh Cuong; Ampem, Grace; Azegrouz, Hind; Balogh, Lajos; Thuróczy, Julianna; Gerling, Ivan C.; Nam, Sorim; Lim, Jong-Seok; Martinez-Ibañez, Juncal; Real, José T.; Paschke, Stephan; Quillet, Raphaëlle; Ayachi, Safia; Simonin, Frédéric; Schneider, E. Marion; Brinkman, Jacqueline A.; Seroogy, Christine M.

    2017-01-01

    The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet–fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage–associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs. PMID:28581443

  3. Sailing on seas of uncertainties: late style and Puccini’s struggle for self-renewal

    Directory of Open Access Journals (Sweden)

    Amir Cohen-Shalev

    2008-10-01

    Full Text Available The popularity of Puccini’s melodramatic operas, often derided by “serious” musicologists, has hindered a more rounded evaluation of his attempt at stylistic change. This paper offers a novel perspective of lifespan creative development in order to move the discussion of Puccini beyond the dichotomy of popular versus high-brow culture. Tracing the aspects of gradual stylistic change that began in The Girl from the Golden West (1910 through the three operas of Il Trittico: Il Tabarro, Suor Angelica, and Gianni Schicchi (1918–1919, the paper then focuses on Puccini’s last opera, Turandot (1926, as exemplifying a potential turn to a reflexive, philosophical style which is very different from the melodramatic, sentimentalist style generally associated with his work. In order to discuss this change as embodying a turn to late style, the paper identifies major stylistic shifts as well as underlying themes in the work of Puccini. Th paper concludes by discussing the case of Puccini as a novel contribution to the discussion of lateness in art, until now reserved to a selected few ‘“old Masters.”

  4. Reversible anionic redox chemistry in high-capacity layered-oxide electrodes

    Science.gov (United States)

    Sathiya, M.; Rousse, G.; Ramesha, K.; Laisa, C. P.; Vezin, H.; Sougrati, M. T.; Doublet, M.-L.; Foix, D.; Gonbeau, D.; Walker, W.; Prakash, A. S.; Ben Hassine, M.; Dupont, L.; Tarascon, J.-M.

    2013-09-01

    Li-ion batteries have contributed to the commercial success of portable electronics and may soon dominate the electric transportation market provided that major scientific advances including new materials and concepts are developed. Classical positive electrodes for Li-ion technology operate mainly through an insertion-deinsertion redox process involving cationic species. However, this mechanism is insufficient to account for the high capacities exhibited by the new generation of Li-rich (Li1+xNiyCozMn(1-x-y-z)O2) layered oxides that present unusual Li reactivity. In an attempt to overcome both the inherent composition and the structural complexity of this class of oxides, we have designed structurally related Li2Ru1-ySnyO3 materials that have a single redox cation and exhibit sustainable reversible capacities as high as 230 mA h g-1. Moreover, they present good cycling behaviour with no signs of voltage decay and a small irreversible capacity. We also unambiguously show, on the basis of an arsenal of characterization techniques, that the reactivity of these high-capacity materials towards Li entails cumulative cationic (Mn+→M(n+1)+) and anionic (O2-→O22-) reversible redox processes, owing to the d-sp hybridization associated with a reductive coupling mechanism. Because Li2MO3 is a large family of compounds, this study opens the door to the exploration of a vast number of high-capacity materials.

  5. Crack-resistant polyimide coating for high-capacity battery anodes

    Science.gov (United States)

    Li, Yingshun; Wang, Shuo; Lee, Pui-Kit; He, Jieqing; Yu, Denis Y. W.

    2017-10-01

    Electrode cracking is a serious problem that hinders the application of many next-generation high-capacity anode materials for lithium-ion batteries. Even though nano-sizing the material can reduce fracturing of individual particles, capacity fading is still observed due to large volume change and loss of contact in the electrode during lithium insertion and extraction. In this study, we design a crack-resistant high-modulus polyimide coating with high compressive strength which can hold multiple particles together during charge and discharge to maintain contact. The effectiveness of the coating is demonstrated on tin dioxide, a high-capacity large-volume-change material that undergoes both alloy and conversion reactions. The polyimide coating improves capacity retention of SnO2 from 80% to 100% after 80 cycles at 250 mA g-1. Stable capacity of 585 mAh g-1 can be obtained even at 500 mA g-1 after 300 cycles. Scanning electron microscopy and in-situ dilatometry confirm that electrode cracking is suppressed and thickness change is reduced with the coating. In addition, the chemically-stable polyimide film can separate the surface from direct contact with electrolyte, improving coulombic efficiency to ∼100%. We expect the novel strategy of suppressing electrode degradation with a crack-resistant coating can also be used for other alloy and conversion-based anodes.

  6. Benzo[a]pyrene impedes self-renewal and differentiation of mesenchymal stem cells and influences fracture healing.

    Science.gov (United States)

    Zhou, Yiqing; Jiang, Rong; An, Liqin; Wang, Hong; Cheng, Sicheng; Qiong, Shi; Weng, Yaguang

    2017-06-01

    Mesenchymal stem cells (MSCs) are implicated in the bone-forming process during fracture repair. Benzo[a]pyrene (BaP)-a cigarette smoke component and powerful motivator of the aryl hydrocarbon receptor (Ahr)-unfavorably influences bone condition and osteoblast differentiation. The first thing we noticed decreases self-renewal and differentiation of human bone marrow mesenchymal stem (hBM-MSCs) from smokers and activates Ahr signaling in MSCs by up-regulating the Ahr target gene cytochrome P450 (CYP) 1B1 expression. In vitro studies, we employed C3H10T1/2 and bone marrow mesenchymal stem cells (BM-MSCs) with BaP and discovered that BaP impaired innate properties of MSCs. Further investigation into MSCs showed that exposure to BaP activated Ahr signaling and inhibited TGF-β1/SMAD4 and TGF-β1/ERK/AKT signaling pathways. Corresponding with the outcomes, tibial fracture calluses produced by BaP-administered rats appeared to delay healing. This effect of BaP was abrogated by resveratrol, a natural Ahr antagonist, in vitro and in vivo. These data demonstrated that Ahr may play a key role in BaP-impaired innate properties by inhibiting SMAD-dependent signaling pathways TGF-β1/SMAD4 and SMAD-independent TGF-β1/ERK/AKT signaling pathways. Furthermore, resveratrol inhibited MSCs from adverse effects caused by BaP. Copyright © 2017. Published by Elsevier B.V.

  7. Differential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Tamm, Christoffer, E-mail: christoffer.tamm@imbim.uu.se; Galito, Sara Pijuan, E-mail: sara.pijuan@imbim.uu.se; Anneren, Cecilia, E-mail: cecilia.anneren@imbim.uu.se

    2012-02-15

    The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying molecular mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approximately 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2. -- Highlights: Black-Right-Pointing-Pointer SFK inhibitor SU6656 induces senescence in mouse ES cells. Black-Right-Pointing-Pointer SU6656 inhibits mitosis in a SFK-independent manner via cross-selectivity for Aurora kinases. Black-Right-Pointing-Pointer SFK inhibitor PP2 impairs cell motility in various cell lines, including mouse ES cells. Black-Right-Pointing-Pointer Ensuing impeded motility, PP2 inhibits proliferation of various cells lines except for mouse ES cells. Black-Right-Pointing-Pointer SFK inhibitors PP2 and PD173952 impede spontaneous differentiation in standard mouse ES culture maintenance.

  8. Differential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors

    International Nuclear Information System (INIS)

    Tamm, Christoffer; Galitó, Sara Pijuan; Annerén, Cecilia

    2012-01-01

    The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying molecular mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approximately 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2. -- Highlights: ► SFK inhibitor SU6656 induces senescence in mouse ES cells. ► SU6656 inhibits mitosis in a SFK-independent manner via cross-selectivity for Aurora kinases. ► SFK inhibitor PP2 impairs cell motility in various cell lines, including mouse ES cells. ► Ensuing impeded motility, PP2 inhibits proliferation of various cells lines except for mouse ES cells. ► SFK inhibitors PP2 and PD173952 impede spontaneous differentiation in standard mouse ES culture maintenance.

  9. The Sensory Components of High-Capacity Iconic Memory and Visual Working Memory

    OpenAIRE

    Bradley, Claire; Pearson, Joel

    2012-01-01

    Early visual memory can be split into two primary components: a high-capacity, short-lived iconic memory followed by a limited-capacity visual working memory that can last many seconds. Whereas a large number of studies have investigated visual working memory for low-level sensory features, much research on iconic memory has used more “high-level” alphanumeric stimuli such as letters or numbers. These two forms of memory are typically examined separately, despite an intrinsic overlap in their...

  10. The sensory components of high-capacity iconic memory and visual working memory

    OpenAIRE

    Claire eBradley; Claire eBradley; Joel ePearson

    2012-01-01

    Early visual memory can be split into two primary components: a high-capacity, short-lived iconic memory followed by a limited-capacity visual working memory that can last many seconds. Whereas a large number of studies have investigated visual working memory for low-level sensory features, much research on iconic memory has used more high-level alphanumeric stimuli such as letters or numbers. These two forms of memory are typically examined separately, despite an intrinsic overlap in their c...

  11. Reassembling and testing of a high-precision heat capacity drop calorimeter. Heat capacity of some polyphenyls at T = 298.15 K

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Luis M.N.B.F., E-mail: lbsantos@fc.up.pt [Centro de Investigacao em Quimica, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto (Portugal); Rocha, Marisa A.A.; Rodrigues, Ana S.M.C. [Centro de Investigacao em Quimica, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto (Portugal); Stejfa, Vojtech; Fulem, Michal [Department of Physical Chemistry, Institute of Chemical Technology, Technicka 5, CZ-166 28 Prague 6 (Czech Republic); Bastos, Margarida [Centro de Investigacao em Quimica, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, 687, 4169-007 Porto (Portugal)

    2011-12-15

    Graphical abstract: Highlights: > We present the reassembling, improvement and testing of a high-precision C{sub p} drop calorimeter. > The apparatus was tested, using benzoic acid and hexafluorobenzene. > The high sensitivity of the apparatus is comparable to the one obtained in adiabatic calorimetry. > Heat capacities at T = 298.15 K of some polyphenyls were measured. > Subtle heat capacity differences among position isomers (ortho, meta, para) were detected. - Abstract: The description of the reassembling and testing of a twin heat conduction, high-precision, drop microcalorimeter for the measurement of heat capacities of small samples are presented. The apparatus, originally developed and used at the Thermochemistry Laboratory, Lund, Sweden, has now been reassembled and modernized, with changes being made as regarding temperature sensors, electronics and data acquisition system. The apparatus was thereafter thoroughly tested, using benzoic acid and hexafluorobenzene as test substances. The accuracy of the C{sub p,m}{sup 0} (298.15 K) data obtained with this apparatus is comparable to that achieved by high-precision adiabatic calorimetry. Here we also present the results of heat capacity measurements on of some polyphenyls (1,2,3-triphenylbenzene, 1,3,5-triphenylbenzene, p-terphenyl, m-terphenyl, o-terphenyl, p-quaterphenyl) at T = 298.15 K, measured with the renewed high precision heat capacity drop calorimeter system. The high resolution and accuracy of the obtained heat capacity data enabled differentiation among the ortho-, meta-, and para-phenyl isomers.

  12. Organizational Self-Renewal

    DEFF Research Database (Denmark)

    Hedman, Jonas; Henningsson, Stefan; Selander, Lisen

    2012-01-01

    Recent research has acknowledged the key role of information systems (IS) in helping build sustainable organizations. Although many organizations have implemented strategies for increased sustainability, empirical evidence for the effects of such strategies is sparse, and the understanding...... from other sustainable initiatives, since they are re-enforcing each other. Third, Green IS initiatives can act as ‘motors’ towards eco-effectiveness, in bridging competing models of organizational effectiveness....

  13. Hollow Carbon Nanofiber-Encapsulated Sulfur Cathodes for High Specific Capacity Rechargeable Lithium Batteries

    KAUST Repository

    Zheng, Guangyuan

    2011-10-12

    Sulfur has a high specific capacity of 1673 mAh/g as lithium battery cathodes, but its rapid capacity fading due to polysulfides dissolution presents a significant challenge for practical applications. Here we report a hollow carbon nanofiber-encapsulated sulfur cathode for effective trapping of polysulfides and demonstrate experimentally high specific capacity and excellent electrochemical cycling of the cells. The hollow carbon nanofiber arrays were fabricated using anodic aluminum oxide (AAO) templates, through thermal carbonization of polystyrene. The AAO template also facilitates sulfur infusion into the hollow fibers and prevents sulfur from coating onto the exterior carbon wall. The high aspect ratio of the carbon nanofibers provides an ideal structure for trapping polysulfides, and the thin carbon wall allows rapid transport of lithium ions. The small dimension of these nanofibers provides a large surface area per unit mass for Li2S deposition during cycling and reduces pulverization of electrode materials due to volumetric expansion. A high specific capacity of about 730 mAh/g was observed at C/5 rate after 150 cycles of charge/discharge. The introduction of LiNO3 additive to the electrolyte was shown to improve the Coulombic efficiency to over 99% at C/5. The results show that the hollow carbon nanofiber-encapsulated sulfur structure could be a promising cathode design for rechargeable Li/S batteries with high specific energy. © 2011 American Chemical Society.

  14. Does visual short-term memory have a high-capacity stage?

    Science.gov (United States)

    Matsukura, Michi; Hollingworth, Andrew

    2011-12-01

    Visual short-term memory (VSTM) has long been considered a durable, limited-capacity system for the brief retention of visual information. However, a recent work by Sligte et al. (Plos One 3:e1699, 2008) reported that, relatively early after the removal of a memory array, a cue allowed participants to access a fragile, high-capacity stage of VSTM that is distinct from iconic memory. In the present study, we examined whether this stage division is warranted by attempting to corroborate the existence of an early, high-capacity form of VSTM. The results of four experiments did not support Sligte et al.'s claim, since we did not obtain evidence for VSTM retention that exceeded traditional estimates of capacity. However, performance approaching that observed in Sligte et al. can be achieved through extensive practice, providing a clear explanation for their findings. Our evidence favors the standard view of VSTM as a limited-capacity system that maintains a few object representations in a relatively durable form.

  15. High-capacity NO2 denuder systems operated at various temperatures (298-473 K).

    Science.gov (United States)

    Wolf, Jan-Christoph; Niessner, Reinhard

    2012-12-01

    In this study, we investigated several coatings for high-temperature, high-capacity, and high-efficiency denuder-based NO(2) removal, with the scope to face the harsh conditions and requirements of automotive exhaust gas sampling. As first coating, we propose a potassium iodide (KI)/polyethylene glycol coating with a high removal efficiency (ε > 98%) for about 2 h and 50 ppm NO(2) at room temperature (298 K). At elevated temperatures (423 K), the initial capacity (100 ppmh) is decreased to 15 ppmh. Furthermore, this is the first proposal of the ionic liquid methyl-butyl-imidazolium iodide ([BMIm(+)][I(-)]) as denuder coating material. At room temperature, this ionic liquid exhibits far greater capacity (300 ppmh) and NO(2) removal efficiency (ε > 99.9%) than KI. Nevertheless, KI exhibits a slightly (~10%) higher capacity at elevated temperatures than [BMIm(+)][I(-)]. Both coatings presented are suitable for applications requiring selective denuding of NO(2) at temperatures up to 423 K.

  16. How high is visual short-term memory capacity for object layout?

    Science.gov (United States)

    Sanocki, Thomas; Sellers, Eric; Mittelstadt, Jeff; Sulman, Noah

    2010-05-01

    Previous research measuring visual short-term memory (VSTM) suggests that the capacity for representing the layout of objects is fairly high. In four experiments, we further explored the capacity of VSTM for layout of objects, using the change detection method. In Experiment 1, participants retained most of the elements in displays of 4 to 8 elements. In Experiments 2 and 3, with up to 20 elements, participants retained many of them, reaching a capacity of 13.4 stimulus elements. In Experiment 4, participants retained much of a complex naturalistic scene. In most cases, increasing display size caused only modest reductions in performance, consistent with the idea of configural, variable-resolution grouping. The results indicate that participants can retain a substantial amount of scene layout information (objects and locations) in short-term memory. We propose that this is a case of remote visual understanding, where observers' ability to integrate information from a scene is paramount.

  17. Developing a Personnel Capacity Indicator for a high turnover Cartographic Production Sector

    Science.gov (United States)

    Mandarino, Flávia; Pessôa, Leonardo A. M.

    2018-05-01

    This paper describes a framework for development of an indicator for human re-sources capacity management in a military organization responsible for nautical chart production. Graphic chart for the results of the model COPPE-COSENZA (Cosenza et al. 2015) is used to properly present the personnel capacity within a high people turnover environment. The specific skills for the nautical charts production allied to the turnover rate require continuous and adequate personnel in-corporation and a capacity building through education and on-the-job training. The adopted approach for the study establishes quantitative values to fulfill quality requirements, and also presents graphically a profile for the human resources on a specific job to facilitate diagnosis and corrective actions.

  18. Key technology studies of GY-20 and GY-40 High-capacity cobalt-60 transport casks

    International Nuclear Information System (INIS)

    Liu Huifang; Zhang Xin

    2012-01-01

    GY-20 and GY-40 high-capacity cobalt-60 transport casks are used to transport cobalt-60 industrial irradiators and cobalt-60 bundles. The radioactive contents have special features of high-activity and high residual heat, so only a few countries such as Canada, England and Russia have design capacity. The key technologies and corresponding solutions were studied for the design and manufacture of the cask taking into account the structural, thermal, mechanics and shield requests. A series of tests prove that the cask structure design, design criteria for lead coating structure and quality control measurements are reasonable and effective, and the cask shield integrity can be ensured for all conditions. The casks have ability to transport high-activity sealed sources safely, and the design of cask satisfies the requirement of design code and standard. It can provide reference for other B type package. (authors)

  19. Radiation and temperature effects on electronic components investigated under the CSTI high capacity power project

    International Nuclear Information System (INIS)

    Schwarze, G.E.; Niedra, J.M.; Frasca, A.J.; Wieserman, W.R.

    1993-01-01

    The effects of nuclear radiation and high temperature environments must be fully known and understood for the electronic components and materials used in both the Power Conditioning and Control subsystem and the reactor Instrumentation and Control subsystem of future high capacity nuclear space power systems. This knowledge is required by the designer of these subsystems in order to develop highly reliable, long-life power systems for future NASA missions. A review and summary of the experimental results obtained for the electronic components and materials investigated under the power management element of the CSTI high capacity power project will be presented in this paper: (1) Neutron, gamma ray, and temperature effects on power semiconductor switches, (2) Temperature and frequency effects on soft magnetic materials; and (3) Temperature effects on rare-earth permanent magnets

  20. Radiation and temperature effects on electronic components investigated under the CSTI High Capacity Power Project

    International Nuclear Information System (INIS)

    Shwarze, G.E.; Wieserman, W.R.

    1994-01-01

    The effects of nuclear radiation and high temperature environments must be fully known and understood for the electronic components and materials used in both the Power Conditioning and Control subsystem and the reactor Instrumentation and Control subsystem of future high capacity nuclear space power systems. This knowledge is required by the designer of these subsystems in order to develop highly reliable, long-life power systems for future NASA missions. A review and summary of the experimental results obtained for the electronic components and materials investigated under the power management element of the CSTI high capacity power project will be presented in this paper: (1) Neutron, gamma ray, and temperature effects on power semiconductor switches, (2) Temperature and frequency effects on soft magnetic materials; and (3) Temperature effects on rare earth permanent magnets

  1. Hydroxylamine hydrochloride: A novel anode material for high capacity lithium-ion batteries

    Science.gov (United States)

    Shao, Lianyi; Shu, Jie; Lao, Mengmeng; Lin, Xiaoting; Wu, Kaiqiang; Shui, Miao; Li, Peng; Long, Nengbing; Ren, Yuanlong

    2014-12-01

    H3NOHCl is used for the first time as anode material for lithium-ion batteries. Electrochemical results show that H3NOHCl with particle size of 4-12 μm can deliver an initial charge capacity of 1018.6 mAh g-1, which is much higher than commercial graphite. After 30 cycles, the reversible capacity can be kept at 676.1 mAh g-1 at 50 mA g-1. Up to 50 cycles, H3NOHCl still maintains a lithium storage capacity of 368.9 mAh g-1. Even cycled at 200 mA g-1, H3NOHCl can deliver a charge capacity of 715.7 mAh g-1. It suggests that H3NOHCl has high lithium storage capacity, excellent cycling stability and outstanding rate performance. Besides, the electrochemical reaction between H3NOHCl and Li is also investigated by various ex-situ techniques. It can be found that H3NOHCl irreversibly decomposes into Li3N and LiCl during the initial discharge process and LiNO2 can be formed after a reverse charge process.

  2. Curtailment in a Highly Renewable Power System and Its Effect on Capacity Factors

    Directory of Open Access Journals (Sweden)

    Alexander Kies

    2016-06-01

    Full Text Available The capacity factor of a power plant is the ratio of generation over its potential generation. It is an important measure to describe wind and solar resources. However, the fluctuating nature of renewable power generation makes it difficult to integrate all generation at times. Whenever generation exceeds the load, curtailment or storage of energy is required. With increasing renewable shares in the power system, the level of curtailment will further increase. In this work, the influence of the curtailment on the capacity factors for a highly renewable German power system is studied. An effective capacity factor is introduced, and the implications for the distribution of renewable power plants are discussed. Three years of highly-resolved weather data were used to model wind and solar power generation. Together with historical load data and a transmission model, a possible future German power system was simulated. It is shown that effective capacity factors for unlimited transmission are strongly reduced by up to 60% (wind and 70% (photovoltaics and therefore of limited value in a highly renewable power system. Furthermore, the results demonstrate that wind power benefits more strongly from a reinforced transmission grid than photovoltaics (PV does.

  3. The sensory components of high-capacity iconic memory and visual working memory.

    Science.gov (United States)

    Bradley, Claire; Pearson, Joel

    2012-01-01

    EARLY VISUAL MEMORY CAN BE SPLIT INTO TWO PRIMARY COMPONENTS: a high-capacity, short-lived iconic memory followed by a limited-capacity visual working memory that can last many seconds. Whereas a large number of studies have investigated visual working memory for low-level sensory features, much research on iconic memory has used more "high-level" alphanumeric stimuli such as letters or numbers. These two forms of memory are typically examined separately, despite an intrinsic overlap in their characteristics. Here, we used a purely sensory paradigm to examine visual short-term memory for 10 homogeneous items of three different visual features (color, orientation and motion) across a range of durations from 0 to 6 s. We found that the amount of information stored in iconic memory is smaller for motion than for color or orientation. Performance declined exponentially with longer storage durations and reached chance levels after ∼2 s. Further experiments showed that performance for the 10 items at 1 s was contingent on unperturbed attentional resources. In addition, for orientation stimuli, performance was contingent on the location of stimuli in the visual field, especially for short cue delays. Overall, our results suggest a smooth transition between an automatic, high-capacity, feature-specific sensory-iconic memory, and an effortful "lower-capacity" visual working memory.

  4. High-capacity method for hiding data in the discrete cosine transform domain

    Science.gov (United States)

    Qazanfari, Kazem; Safabakhsh, Reza

    2013-10-01

    Steganography is the art and science of hiding data in different media such as texts, audios, images, and videos. Data hiding techniques are generally divided into two groups: spatial and frequency domain techniques. Spatial domain methods generally have low security and, as a result, are less attractive to researchers. Discrete cosine transform (DCT) is the most common transform domain used in steganography and JPEG compression. Since a large number of the DCT coefficients of JPEG images are zero, the capacity of DCT domain-based steganography methods is not very high. We present a high-capacity method for hiding messages in the DCT domain. We describe the method in two classes where the receiver has and where the receiver does not have the cover image. In each class, we consider three cases for each coefficient. By considering n coefficients, there are 3n different situations. The method embeds ⌊log2 3n⌋ bits in these n coefficients. We show that the maximum reachable capacity by our method is 58% higher than the other general steganography methods. Experimental results show that the histogram-based steganalysis methods cannot detect the stego images produced by the proposed method while the capacity is increased significantly.

  5. On-demand high-capacity ride-sharing via dynamic trip-vehicle assignment.

    Science.gov (United States)

    Alonso-Mora, Javier; Samaranayake, Samitha; Wallar, Alex; Frazzoli, Emilio; Rus, Daniela

    2017-01-17

    Ride-sharing services are transforming urban mobility by providing timely and convenient transportation to anybody, anywhere, and anytime. These services present enormous potential for positive societal impacts with respect to pollution, energy consumption, congestion, etc. Current mathematical models, however, do not fully address the potential of ride-sharing. Recently, a large-scale study highlighted some of the benefits of car pooling but was limited to static routes with two riders per vehicle (optimally) or three (with heuristics). We present a more general mathematical model for real-time high-capacity ride-sharing that (i) scales to large numbers of passengers and trips and (ii) dynamically generates optimal routes with respect to online demand and vehicle locations. The algorithm starts from a greedy assignment and improves it through a constrained optimization, quickly returning solutions of good quality and converging to the optimal assignment over time. We quantify experimentally the tradeoff between fleet size, capacity, waiting time, travel delay, and operational costs for low- to medium-capacity vehicles, such as taxis and van shuttles. The algorithm is validated with ∼3 million rides extracted from the New York City taxicab public dataset. Our experimental study considers ride-sharing with rider capacity of up to 10 simultaneous passengers per vehicle. The algorithm applies to fleets of autonomous vehicles and also incorporates rebalancing of idling vehicles to areas of high demand. This framework is general and can be used for many real-time multivehicle, multitask assignment problems.

  6. Extreme genetic structure in a social bird species despite high dispersal capacity.

    Science.gov (United States)

    Morinha, Francisco; Dávila, José A; Bastos, Estela; Cabral, João A; Frías, Óscar; González, José L; Travassos, Paulo; Carvalho, Diogo; Milá, Borja; Blanco, Guillermo

    2017-05-01

    Social barriers have been shown to reduce gene flow and contribute to genetic structure among populations in species with high cognitive capacity and complex societies, such as cetaceans, apes and humans. In birds, high dispersal capacity is thought to prevent population divergence unless major geographical or habitat barriers induce isolation patterns by dispersal, colonization or adaptation limitation. We report that Iberian populations of the red-billed chough, a social, gregarious corvid with high dispersal capacity, show a striking degree of genetic structure composed of at least 15 distinct genetic units. Monitoring of marked individuals over 30 years revealed that long-distance movements over hundreds of kilometres are common, yet recruitment into breeding populations is infrequent and highly philopatric. Genetic differentiation is weakly related to geographical distance, and habitat types used are overall qualitatively similar among regions and regularly shared by individuals of different populations, so that genetic structure is unlikely to be due solely to isolation by distance or isolation by adaptation. Moreover, most population nuclei showed relatively high levels of genetic diversity, suggesting a limited role for genetic drift in significantly differentiating populations. We propose that social mechanisms may underlie this unprecedented level of genetic structure in birds through a pattern of isolation by social barriers not yet described, which may have driven this remarkable population divergence in the absence of geographical and environmental barriers. © 2017 John Wiley & Sons Ltd.

  7. Densities, viscosities, and isobaric heat capacities of the system (1-butanol + cyclohexane) at high pressures

    International Nuclear Information System (INIS)

    Torín-Ollarves, Geraldine A.; Martín, M. Carmen; Chamorro, César R.; Segovia, José J.

    2014-01-01

    Highlights: • The densities of cyclohexane and its mixtures with 1-butanol were measured. • The excess molar volumes were calculated and correlated. • The viscosities were measured at atmospheric pressure. • The isobaric heat capacities were measured at p = (0.1 to 25) MPa at T = (293.15 and 313.15) K. • A positive deviation from the ideal behavior is observed. - Abstract: The cyclohexane and the system of 1-butanol + cyclohexane have been characterized using densities, viscosities and isobaric heat capacities measurements. For that, the densities were measured in a high-pressure vibrating tube densimeter at five temperatures from (293.15 to 333.15) K and pressures up to 100 MPa. The measurements were correlated with the empirical Tamman–Tait equation. Moreover, the isobaric heat capacities of the binary system were measured in a high-pressure automated flow calorimeter at T = (293.15 and 313.15) K and pressures up to 25 MPa for pure cyclohexane and in admixture with 1-butanol. The excess molar heat capacities were assessed for the mixture and a positive deviation from the ideality was obtained, except for a small part in the region rich in alkanol. The viscosity measurements were carried out, at the calorimeter conditions, for correcting the experimental values of isobaric heat capacities due to friction along the tube. The viscosity was measured at atmospheric pressure in a Stabinger Anton Paar SVM 3000 viscometer in the temperature range of (293.15 to 333.15) K for cyclohexane and the mixtures. At high pressure, the viscosities were estimated using Lucas method

  8. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  9. Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish.

    Science.gov (United States)

    Lin, Qiaohong; Mei, Jie; Li, Zhi; Zhang, Xuemei; Zhou, Li; Gui, Jian-Fang

    2017-11-01

    Spermatogenesis is a fundamental process in male reproductive biology and depends on precise balance between self-renewal and differentiation of male germ cells. However, the regulative factors for controlling the balance are poorly understood. In this study, we examined the roles of amh and dmrt1 in male germ cell development by generating their mutants with Crispr/Cas9 technology in zebrafish. Amh mutant zebrafish displayed a female-biased sex ratio, and both male and female amh mutants developed hypertrophic gonads due to uncontrolled proliferation and impaired differentiation of germ cells. A large number of proliferating spermatogonium-like cells were observed within testicular lobules of the amh -mutated testes, and they were demonstrated to be both Vasa- and PH3-positive. Moreover, the average number of Sycp3- and Vasa-positive cells in the amh mutants was significantly lower than in wild-type testes, suggesting a severely impaired differentiation of male germ cells. Conversely, all the dmrt1 -mutated testes displayed severe testicular developmental defects and gradual loss of all Vasa-positive germ cells by inhibiting their self-renewal and inducing apoptosis. In addition, several germ cell and Sertoli cell marker genes were significantly downregulated, whereas a prominent increase of Insl3-positive Leydig cells was revealed by immunohistochemical analysis in the disorganized dmrt1 -mutated testes. Our data suggest that amh might act as a guardian to control the balance between proliferation and differentiation of male germ cells, whereas dmrt1 might be required for the maintenance, self-renewal, and differentiation of male germ cells. Significantly, this study unravels novel functions of amh gene in fish. Copyright © 2017 by the Genetics Society of America.

  10. Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells.

    Science.gov (United States)

    Xu, Zhuojin; Robitaille, Aaron M; Berndt, Jason D; Davidson, Kathryn C; Fischer, Karin A; Mathieu, Julie; Potter, Jennifer C; Ruohola-Baker, Hannele; Moon, Randall T

    2016-10-18

    In both mice and humans, pluripotent stem cells (PSCs) exist in at least two distinct states of pluripotency, known as the naïve and primed states. Our understanding of the intrinsic and extrinsic factors that enable PSCs to self-renew and to transition between different pluripotent states is important for understanding early development. In mouse embryonic stem cells (mESCs), Wnt proteins stimulate mESC self-renewal and support the naïve state. In human embryonic stem cells (hESCs), Wnt/β-catenin signaling is active in naïve-state hESCs and is reduced or absent in primed-state hESCs. However, the role of Wnt/β-catenin signaling in naïve hESCs remains largely unknown. Here, we demonstrate that inhibition of the secretion of Wnts or inhibition of the stabilization of β-catenin in naïve hESCs reduces cell proliferation and colony formation. Moreover, we show that addition of recombinant Wnt3a partially rescues cell proliferation in naïve hESCs caused by inhibition of Wnt secretion. Notably, inhibition of Wnt/β-catenin signaling in naïve hESCs did not cause differentiation. Instead, it induced primed hESC-like proteomic and metabolic profiles. Thus, our results suggest that naïve hESCs secrete Wnts that activate autocrine or paracrine Wnt/β-catenin signaling to promote efficient self-renewal and inhibit the transition to the primed state.

  11. Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway.

    Science.gov (United States)

    Barnawi, Rayanah; Al-Khaldi, Samiyah; Majed Sleiman, Ghida; Sarkar, Abdullah; Al-Dhfyan, Abdullah; Al-Mohanna, Falah; Ghebeh, Hazem; Al-Alwan, Monther

    2016-12-01

    An emerging dogma shows that tumors are initiated and maintained by a subpopulation of cancer cells that hijack some stem cell features and thus referred to as "cancer stem cells" (CSCs). The exact mechanism that regulates the maintenance of CSC pool remains largely unknown. Fascin is an actin-bundling protein that we have previously demonstrated to be a major regulator of breast cancer chemoresistance and metastasis, two cardinal features of CSCs. Here, we manipulated fascin expression in breast cancer cell lines and used several in vitro and in vivo approaches to examine the relationship between fascin expression and breast CSCs. Fascin knockdown significantly reduced stem cell-like phenotype (CD44 hi /CD24 lo and ALDH + ) and reversal of epithelial to mesenchymal transition. Interestingly, expression of the embryonic stem cell transcriptional factors (Oct4, Nanog, Sox2, and Klf4) was significantly reduced when fascin expression was down-regulated. Functionally, fascin-knockdown cells were less competent in forming colonies and tumorspheres, consistent with lower basal self-renewal activity and higher susceptibility to chemotherapy. Fascin effect on CSC chemoresistance and self-renewability was associated with Notch signaling. Activation of Notch induced the relevant downstream targets predominantly in the fascin-positive cells. Limiting-dilution xenotransplantation assay showed higher frequency of tumor-initiating cells in the fascin-positive group. Collectively, our data demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. Stem Cells 2016;34:2799-2813 Video Highlight: https://youtu.be/GxS4fJ_Ow-o. © 2016 AlphaMed Press.

  12. Ligand-enhanced electrokinetic remediation of metal-contaminated marine sediments with high acid buffering capacity.

    Science.gov (United States)

    Masi, Matteo; Iannelli, Renato; Losito, Gabriella

    2016-06-01

    The suitability of electrokinetic remediation for removing heavy metals from dredged marine sediments with high acid buffering capacity was investigated. Laboratory-scale electrokinetic remediation experiments were carried out by applying two different voltage gradients to the sediment (0.5 and 0.8 V/cm) while circulating water or two different chelating agents at the electrode compartments. Tap water, 0.1 M citric acid and 0.1 M ethylenediaminetetraacetic acid (EDTA) solutions were used respectively. The investigated metals were Zn, Pb, V, Ni and Cu. In the unenhanced experiment, the acid front could not propagate due to the high acid buffering capacity of the sediments; the production of OH(-) ions at the cathode resulted in a high-pH environment causing the precipitation of CaCO3 and metal hydroxides. The use of citric acid prevented the formation of precipitates, but solubilisation and mobilisation of metal species were not sufficiently achieved. Metal removal was relevant when EDTA was used as the conditioning agent, and the electric potential was raised up to 0.8 V/cm. EDTA led to the formation of negatively charged complexes with metals which migrated towards the anode compartment by electromigration. This result shows that metal removal from sediments with high acid buffering capacity may be achieved by enhancing the electrokinetic process by EDTA addition when the acidification of the medium is not economically and/or environmentally sustainable.

  13. Evaluation of high frequency ground motion effects on the seismic capacity of NPP equipments

    International Nuclear Information System (INIS)

    Choi, In Kil; Seo, Jeong Moon; Choun, Young Sun

    2003-04-01

    In this study, the uniform hazard spectrum for the example Korean nuclear power plants sites were developed and compared with various response spectra used in past seismic PRA and SMA. It shows that the high frequency ground motion effects should be considered in seismic safety evaluations. The floor response spectra were developed using the direct generation method that can develop the floor response spectra from the input response spectrum directly with only the dynamic properties of structures obtained from the design calculation. Most attachment of the equipments to the structure has a minimum distortion capacity. This makes it possible to drop the effective frequency of equipment to low frequency before it is severely damaged. The results of this study show that the high frequency ground motion effects on the floor response spectra were significant, and the effects should be considered in the SPRA and SMA for the equipments installed in a building. The high frequency ground motion effects are more important for the seismic capacity evaluation of functional failure modes. The high frequency ground motion effects on the structural failure of equipments that attached to the floor by welding can be reduced by the distortion capacity of welded anchorage

  14. Carbon−Silicon Core−Shell Nanowires as High Capacity Electrode for Lithium Ion Batteries

    KAUST Repository

    Cui, Li-Feng

    2009-09-09

    We introduce a novel design of carbon-silicon core-shell nanowires for high power and long life lithium battery electrodes. Amorphous silicon was coated onto carbon nanofibers to form a core-shell structure and the resulted core-shell nanowires showed great performance as anode material. Since carbon has a much smaller capacity compared to silicon, the carbon core experiences less structural stress or damage during lithium cycling and can function as a mechanical support and an efficient electron conducting pathway. These nanowires have a high charge storage capacity of ∼2000 mAh/g and good cycling life. They also have a high Coulmbic efficiency of 90% for the first cycle and 98-99.6% for the following cycles. A full cell composed of LiCoO2 cathode and carbon-silicon core-shell nanowire anode is also demonstrated. Significantly, using these core-shell nanowires we have obtained high mass loading and an area capacity of ∼4 mAh/cm2, which is comparable to commercial battery values. © 2009 American Chemical Society.

  15. Estimation of Parameters Obtained by Electrochemical Impedance Spectroscopy on Systems Containing High Capacities

    Directory of Open Access Journals (Sweden)

    Mirjana Rajčić Vujasinović

    2009-09-01

    Full Text Available Electrochemical systems with high capacities demand devices for electrochemical impedance spectroscopy (EIS with ultra-low frequencies (in order of mHz, that are almost impossible to accomplish with analogue techniques, but this becomes possible by using a computer technique and accompanying digital equipment. Recently, an original software and hardware for electrochemical measurements, intended for electrochemical systems exhibiting high capacities, such as supercapacitors, has been developed. One of the included methods is EIS. In this paper, the method of calculation of circuit parameters from an EIS curve is described. The results of testing on a physical model of an electrochemical system, constructed of known elements (including a 1.6 F capacitor in a defined arrangement, proved the validity of the system and the method.

  16. High-Capacity Hybrid Optical Fiber-Wireless Communications Links in Access Networks

    DEFF Research Database (Denmark)

    Pang, Xiaodan

    of broadband services access. To realize the seamless convergence between the two network segments, the lower capacity of wireless systems need to be increased to match the continuously increasing bandwidth of fiber-optic systems. The research works included in this thesis are devoted to experimental...... investigations of photonic-wireless links with record high capacities to fulfill the requirements of next generation hybrid optical fiber-wireless access networks. The main contributions of this thesis have expanded the state-of-the-art in two main areas: high speed millimeter-wave (mm-wave) communication links......Integration between fiber-optic and wireless communications systems in the "last mile" access networks is currently considered as a promising solution for both service providers and users, in terms of minimizing deployment cost, shortening upgrading period and increasing mobility and flexibility...

  17. A micro-structured Si-based electrodes for high capacity electrical double layer capacitors

    International Nuclear Information System (INIS)

    Krikscikas, Valdas; Oguchi, Hiroyuki; Hara, Motoaki; Kuwano, Hiroki; Yanazawa, Hiroshi

    2014-01-01

    We challenged to make basis for Si electrodes of electric double layer capacitors (EDLC) used as a power source of micro-sensor nodes. Mcroelectromechanical systems (MEMS) processes were successfully introduced to fabricate micro-structured Si-based electrodes to obtain high surface area which leads to high capacity of EDLCs. Study of fundamental properties revealed that the microstructured electrodes benefit from good wettability to electrolytes, but suffer from electric resistance. We found that this problem can be solved by metal-coating of the electrode surface. Finally we build an EDLC consisting of Au-coated micro-structured Si electrodes. This EDLC showed capacity of 14.3 mF/cm 2 , which is about 530 times larger than that of an EDLC consisting of flat Au electrodes

  18. Optical intensity modulation direct detection versus heterodyne detection: A high-SNR capacity comparison

    KAUST Repository

    Chaaban, Anas

    2016-09-15

    An optical wireless communications system which employs either intensity-modulation and direct-detection (IM-DD) or heterodyne detection (HD) is considered. IM-DD has lower complexity and cost than HD, but on the other hand, has lower capacity. It is therefore interesting to investigate the capacity gap between the two systems. The main focus of this paper is to investigate this gap at high SNR. Bounds on this gap are established for two cases: between IM-DD and HD, and between IM-DD and an HD-PAM which is an HD system employing pulse-amplitude modulation (PAM). While the gap between IM-DD and HD increases as the signal-to-noise ratio (SNR) increases, the gap between IM-DD and an HD-PAM is upper bounded by a constant at high SNR. © 2015 IEEE.

  19. Load carrying capacity of keyed joints reinforced with high strength wire rope loops

    DEFF Research Database (Denmark)

    Jørgensen, Henrik B.; Hoang, Linh Cao

    2015-01-01

    friendly shear connection can be obtained by replacing the U-bars with high strength looped wire ropes. The wire ropes have the advantage of being flexible (they have virtually no bending stiffness) which makes installation of wall elements much easier. The looped wire ropes are usually pre-installed in so......-called wire boxes which are embedded in the precast wall elements. Once the joint is grouted with mortar, the boxes will function as shear keys and the overlapping wire loops will function as transverse reinforcement that replaces the U-bars. This paper presents a rigid-plastic upper bound model to determine...... the shear capacity of wire loop connections. Tests have shown that the shear capacity of such joints – due to the relatively high tensile strength of the wire ropes - is more prone to be governed by fracture of the joint mortar in combination with yielding of the locking bar. To model this type of failure...

  20. High-Capacity Hydrogen-Based Green-Energy Storage Solutions For The Grid Balancing

    Science.gov (United States)

    D'Errico, F.; Screnci, A.

    One of the current main challenges in green-power storage and smart grids is the lack of effective solutions for accommodating the unbalance between renewable energy sources, that offer intermittent electricity supply, and a variable electricity demand. Energy management systems have to be foreseen for the near future, while they still represent a major challenge. Integrating intermittent renewable energy sources, by safe and cost-effective energy storage systems based on solid state hydrogen is today achievable thanks to recently some technology breakthroughs. Optimized solid storage method made of magnesium-based hydrides guarantees a very rapid absorption and desorption kinetics. Coupled with electrolyzer technology, high-capacity storage of green-hydrogen is therefore practicable. Besides these aspects, magnesium has been emerging as environmentally friend energy storage method to sustain integration, monitoring and control of large quantity of GWh from high capacity renewable generation in the EU.

  1. Optical intensity modulation direct detection versus heterodyne detection: A high-SNR capacity comparison

    KAUST Repository

    Chaaban, Anas; Alouini, Mohamed-Slim

    2016-01-01

    An optical wireless communications system which employs either intensity-modulation and direct-detection (IM-DD) or heterodyne detection (HD) is considered. IM-DD has lower complexity and cost than HD, but on the other hand, has lower capacity. It is therefore interesting to investigate the capacity gap between the two systems. The main focus of this paper is to investigate this gap at high SNR. Bounds on this gap are established for two cases: between IM-DD and HD, and between IM-DD and an HD-PAM which is an HD system employing pulse-amplitude modulation (PAM). While the gap between IM-DD and HD increases as the signal-to-noise ratio (SNR) increases, the gap between IM-DD and an HD-PAM is upper bounded by a constant at high SNR. © 2015 IEEE.

  2. Peel and pulp of baru (Dipteryx Alata Vog. provide high fiber, phenolic content and antioxidant capacity

    Directory of Open Access Journals (Sweden)

    Gabriela de Lima SANTIAGO

    2018-03-01

    Full Text Available Abstract Baru (Dipteryx alata Vog. is a native fruit of the Brazilian Savannah that can be used in the food industry and may contribute to the economy of the Brazilian Midwest. The proximate composition, the phenolic content and the antioxidant capacity of the peel, pulp and raw and roasted baru almond were examined and compared. Peel showed higher concentrations of dietary fibers (24.1 g/100 g followed by pulp and roasted almond (18 g/100 g and 16 g/100 g, respectively, and raw almond (12.0 g/100 g. However, the almonds presented the highest lipid and protein concentrations compared to baru peel and pulp. In addition, raw almond showed the highest total phenolic contents (1,107.0 mg GAE/100 g and antioxidant capacity, but the roasted almond, and baru peel with its pulp, also presented high phenolic contents. The correlation coefficients between phenolic content and antioxidant capacity (via ABTS and FRAP were strong and significant. The chemical composition of baru peel has not previously been reported. The results showed promising prospects for the consumption of baru pulp with its peel, the fruit component richest in fiber, whose phenolic content and antioxidant capacity are comparable to those of the baru almond.

  3. Abiotic and biotic determinants of leaf carbon exchange capacity from tropical to high boreal biomes

    Science.gov (United States)

    Smith, N. G.; Dukes, J. S.

    2016-12-01

    Photosynthesis and respiration on land represent the two largest fluxes of carbon dioxide between the atmosphere and the Earth's surface. As such, the Earth System Models that are used to project climate change are high sensitive to these processes. Studies have found that much of this uncertainty is due to the formulation and parameterization of plant photosynthetic and respiratory capacity. Here, we quantified the abiotic and biotic factors that determine photosynthetic and respiratory capacity at large spatial scales. Specifically, we measured the maximum rate of Rubisco carboxylation (Vcmax), the maximum rate of Ribulose-1,5-bisphosphate regeneration (Jmax), and leaf dark respiration (Rd) in >600 individuals of 98 plant species from the tropical to high boreal biomes of Northern and Central America. We also measured a bevy of covariates including plant functional type, leaf nitrogen content, short- and long-term climate, leaf water potential, plant size, and leaf mass per area. We found that plant functional type and leaf nitrogen content were the primary determinants of Vcmax, Jmax, and Rd. Mean annual temperature and mean annual precipitation were not significant predictors of these rates. However, short-term climatic variables, specifically soil moisture and air temperature over the previous 25 days, were significant predictors and indicated that heat and soil moisture deficits combine to reduce photosynthetic capacity and increase respiratory capacity. Finally, these data were used as a model benchmarking tool for the Community Land Model version 4.5 (CLM 4.5). The benchmarking analyses determined errors in the leaf nitrogen allocation scheme of CLM 4.5. Under high leaf nitrogen levels within a plant type the model overestimated Vcmax and Jmax. This result suggested that plants were altering their nitrogen allocation patterns when leaf nitrogen levels were high, an effect that was not being captured by the model. These data, taken with models in mind

  4. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  5. Charge Modulation in Graphitic Carbon Nitride as a Switchable Approach to High-Capacity Hydrogen Storage.

    Science.gov (United States)

    Tan, Xin; Kou, Liangzhi; Tahini, Hassan A; Smith, Sean C

    2015-11-01

    Electrical charging of graphitic carbon nitride nanosheets (g-C4 N3 and g-C3 N4 ) is proposed as a strategy for high-capacity and electrocatalytically switchable hydrogen storage. Using first-principle calculations, we found that the adsorption energy of H2 molecules on graphitic carbon nitride nanosheets is dramatically enhanced by injecting extra electrons into the adsorbent. At full hydrogen coverage, the negatively charged graphitic carbon nitride achieves storage capacities up to 6-7 wt %. In contrast to other hydrogen storage approaches, the storage/release occurs spontaneously once extra electrons are introduced or removed, and these processes can be simply controlled by switching on/off the charging voltage. Therefore, this approach promises both facile reversibility and tunable kinetics without the need of specific catalysts. Importantly, g-C4 N3 has good electrical conductivity and high electron mobility, which can be a very good candidate for electron injection/release. These predictions may prove to be instrumental in searching for a new class of high-capacity hydrogen storage materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Study on the flow nonuniformity in a high capacity Stirling pulse tube cryocooler

    Science.gov (United States)

    You, X.; Zhi, X.; Duan, C.; Jiang, X.; Qiu, L.; Li, J.

    2017-12-01

    High capacity Stirling-type pulse tube cryocoolers (SPTC) have promising applications in high temperature superconductive motor and gas liquefaction. However, with the increase of cooling capacity, its performance deviates from well-accepted one-dimensional model simulation, such as Sage and Regen, mainly due to the strong field nonuniformity. In this study, several flow straighteners placed at both ends of the pulse tube are investigated to improve the flow distribution. A two-dimensional model of the pulse tube based on the computational fluid dynamics (CFD) method has been built to study the flow distribution of the pulse tube with different flow straighteners including copper screens, copper slots, taper transition and taper stainless slot. A SPTC set-up which has more than one hundred Watts cooling power at 80 K has been built and tested. The flow straighteners mentioned above have been applied and tested. The results show that with the best flow straightener the cooling performance of the SPTC can be significantly improved. Both CFD simulation and experiment show that the straighteners have impacts on the flow distribution and the performance of the high capacity SPTC.

  7. The sensory components of high-capacity iconic memory and visual working memory

    Directory of Open Access Journals (Sweden)

    Claire eBradley

    2012-09-01

    Full Text Available Early visual memory can be split into two primary components: a high-capacity, short-lived iconic memory followed by a limited-capacity visual working memory that can last many seconds. Whereas a large number of studies have investigated visual working memory for low-level sensory features, much research on iconic memory has used more high-level alphanumeric stimuli such as letters or numbers. These two forms of memory are typically examined separately, despite an intrinsic overlap in their characteristics. Here, we used a purely sensory paradigm to examine visual short-term memory for 10 homogeneous items of 3 different visual features (colour, orientation and motion across a range of durations from 0 to 6 seconds. We found that the amount of information stored in iconic memory is smaller for motion than for colour or orientation. Performance declined exponentially with longer storage durations and reached chance levels after ~2 seconds. Further experiments showed that performance for the 10 items at 1 second was contingent on unperturbed attentional resources. In addition, for orientation stimuli, performance was contingent on the location of stimuli in the visual field, especially for short cue delays. Overall, our results suggest a smooth transition between an automatic, high-capacity, feature-specific sensory-iconic memory and an effortful ‘lower-capacity’ visual working memory.

  8. High-Density Near-Field Readout over 50 GB Capacity Using Solid Immersion Lens with High Refractive Index

    Science.gov (United States)

    Shinoda, Masataka; Saito, Kimihiro; Kondo, Takao; Ishimoto, Tsutomu; Nakaoki, Ariyoshi

    2003-02-01

    We have investigated high-density near-field readout using a solid immersion lens with a high refractive index. By using a glass material with a high refractive index of 2.08, we developed an optical pick-up with the effective numerical aperture of 1.8. We could observe a clear eye pattern for a 50 GB capacity disc in 120 mm diameter. We confirmed that the near-field readout system is promising method of realizing a high-density optical disc system.

  9. Binders and Hosts for High-Capacity Lithium-ion Battery Anodes

    Science.gov (United States)

    Dufficy, Martin Kyle

    Lithium-ion batteries (LIBs) are universal electrochemical energy storage devices that have revolutionized our mobile society. Nonetheless, societal and technological advances drive consumer demand for LIBs with enhanced electrochemical performance, such as higher charge capacity and longer life, compared to conventional LIBs. One method to enhance LIB performance is to replace graphite, the industry standard anode since commercialization of LIBs in 1991, with high-charge capacity materials. Implementing high-capacity anode materials such as tin, silicon, and manganese vanadates, to LIBs presents challenges; Li-insertion is destructive to anode framework, and increasing capacity increases structural strains that pulverize anode materials and results in a short-cycle life. This thesis reports on various methods to extended the cycle life of high-capacity materials. Most of the work is conducted on nano-sized anode materials to reduce Li and electron transport pathway length (facilitating charge-transfer) and reduce strains from volume expansions (preserving anode structure). The first method involves encapsulating tin particles into a graphene-containing carbon nanofiber (CNF) matrix. The composite-CNF matrix houses tin particles to assume strains from tin-volume expansions and produces favorable surface-electrolyte chemistries for stable charge-discharge cycling. Before tin addition, graphene-containing CNFs are produced and assessed as anode materials for LIBs. Graphene addition to CNFs improves electronic and mechanical properties of CNFs. Furthermore, the 2-D nature of graphene provides Li-binding sites to enhance composite-CNF both first-cycle and high-rate capacities > 150% when compared to CNFs in the absence of graphene. With addition of Sn, we vary loadings and thermal production temperature to elucidate structure-composition relationships of tin and graphene-containing CNF electrodes that lead to increased capacity retention. Of note, electrodes containing

  10. Energy Efficiency and Capacity Tradeoff in Cloud Radio Access Network of High-Speed Railways

    Directory of Open Access Journals (Sweden)

    Shichao Li

    2017-01-01

    Full Text Available To meet the increasing demand of high-data-rate services of high-speed railway (HSR passengers, cloud radio access network (C-RAN is proposed. This paper investigates the tradeoff between energy efficiency (EE performance and capacity in C-RAN of HSR. Considering that the train location can be predicted, we propose a predictable path loss based time domain power allocation method (PPTPA to improve EE performance of HSR communication system. First, we consider that the communication system of HSR only bears the passenger information services (PISs. The energy-efficient power allocation problem with delay constraint is studied. The formulated problem is nonconvex. To deal with it, an equivalent convex problem is reformulated. Based on PPTPA, we propose an iterative algorithm to improve the EE performance. Second, we consider that the PISs and the train control services (TCSs are all bore. A capacity optimization problem with joint EE and services transmission delay constraints is formulated. Based on PPTPA, we propose a hybrid power allocation scheme to improve the capacity of the system. Finally, we analyze the effect of small-scale fading on EE performance. The effectiveness of the proposed power allocation algorithm is validated by HSR channel measurement trace based emulation results and extensive simulation results.

  11. An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice.

    Science.gov (United States)

    Ma, Sihui; Huang, Qingyi; Yada, Koichi; Liu, Chunhong; Suzuki, Katsuhiko

    2018-05-25

    Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

  12. Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings.

    Science.gov (United States)

    Sabiiti, W; Mtafya, B; Kuchaka, D; Azam, K; Viegas, S; Mdolo, A; Farmer, E C W; Khonga, M; Evangelopoulos, D; Honeyborne, I; Rachow, A; Heinrich, N; Ntinginya, N E; Bhatt, N; Davies, G R; Jani, I V; McHugh, T D; Kibiki, G; Hoelscher, M; Gillespie, S H

    2016-08-01

    The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.

  13. High capacity fiber optic sensor networks using hybrid multiplexing techniques and their applications

    Science.gov (United States)

    Sun, Qizhen; Li, Xiaolei; Zhang, Manliang; Liu, Qi; Liu, Hai; Liu, Deming

    2013-12-01

    Fiber optic sensor network is the development trend of fiber senor technologies and industries. In this paper, I will discuss recent research progress on high capacity fiber sensor networks with hybrid multiplexing techniques and their applications in the fields of security monitoring, environment monitoring, Smart eHome, etc. Firstly, I will present the architecture of hybrid multiplexing sensor passive optical network (HSPON), and the key technologies for integrated access and intelligent management of massive fiber sensor units. Two typical hybrid WDM/TDM fiber sensor networks for perimeter intrusion monitor and cultural relics security are introduced. Secondly, we propose the concept of "Microstructure-Optical X Domin Refecltor (M-OXDR)" for fiber sensor network expansion. By fabricating smart micro-structures with the ability of multidimensional encoded and low insertion loss along the fiber, the fiber sensor network of simple structure and huge capacity more than one thousand could be achieved. Assisted by the WDM/TDM and WDM/FDM decoding methods respectively, we built the verification systems for long-haul and real-time temperature sensing. Finally, I will show the high capacity and flexible fiber sensor network with IPv6 protocol based hybrid fiber/wireless access. By developing the fiber optic sensor with embedded IPv6 protocol conversion module and IPv6 router, huge amounts of fiber optic sensor nodes can be uniquely addressed. Meanwhile, various sensing information could be integrated and accessed to the Next Generation Internet.

  14. Towards high-reliability organising in healthcare: a strategy for building organisational capacity.

    Science.gov (United States)

    Aboumatar, Hanan J; Weaver, Sallie J; Rees, Dianne; Rosen, Michael A; Sawyer, Melinda D; Pronovost, Peter J

    2017-08-01

    In a high-reliability organisation (HRO), safety and quality (SQ) is an organisational priority, and all workforce members are engaged, continuously learning and improving their work. To build organisational capacity for SQ work, we have developed a role-tailored capacity-building framework that we are currently employing at the Johns Hopkins Armstrong Institute for Patient Safety and Quality as part of an organisational strategy towards HRO. This framework considers organisation-wide competencies for SQ that includes all staff and faculty and is integrated into a broader organisation-wide operating management system for improving quality. In this framework, achieving safe, high-quality care is connected to healthcare workforce preparedness. Capacity-building efforts are tailored to the needs of distinct groups within the workforce that fall within three categories: (1) front-line providers and staff, (2) managers and local improvement personnel and (3) SQ leaders and experts. In this paper we describe this framework, our implementation efforts to date, challenges met and lessons learnt. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Review on anionic redox for high-capacity lithium- and sodium-ion batteries

    International Nuclear Information System (INIS)

    Zhao, Chenglong; Lu, Yaxiang; Hu, Yong-Sheng; Chen, Liquan; Wang, Qidi; Li, Baohua

    2017-01-01

    Rechargeable batteries, especially lithium-ion batteries, are now widely used as power sources for portable electronics and electric vehicles, but material innovations are still needed to satisfy the increasing demand for larger energy density. Recently, lithium- and sodium-rich electrode materials, including the A 2 MO 3 -family layered compounds (A  =  Li, Na; M  =  Mn 4+ , Ru 4+ , etc), have been extensively studied as potential high-capacity electrode materials for a cumulative cationic and anionic redox activity. Negatively charged oxide ions can potentially donate electrons to compensate for the absence of oxidable transition metals as a redox center to further increase the reversible capacity. Understanding and controlling the state-of-the-art anionic redox processes is pivotal for the design of advanced energy materials, highlighted in rechargeable batteries. Hence, experimental and theoretical approaches have been developed to consecutively study the diverting processes, states, and structures involved. In this review, we attempt to present a literature overview and provide insight into the reaction mechanism with respect to the anionic redox processes, proposing some opinions as target oriented. It is hoped that, through this discussion, the search for anionic redox electrode materials with high-capacity rechargeable batteries can be advanced, and practical applications realized as soon as possible. (topical review)

  16. An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice

    Directory of Open Access Journals (Sweden)

    Sihui Ma

    2018-05-01

    Full Text Available Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

  17. Final Scientific/Technical Report for Low Cost, High Capacity Non- Intercalation Chemistry Automotive Cells

    Energy Technology Data Exchange (ETDEWEB)

    Berdichevsky, Gene [Sila Nanotechnologies, Inc., Alameda, CA (United States)

    2017-09-08

    Commercial Li-ion batteries typically use Ni- and Co-based intercalation cathodes. As the demand for improved performance from batteries increases, these cathode materials will no longer be able to provide the desired energy storage characteristics since they are currently approaching their theoretical limits. Conversion cathode materials are prime candidates for improvement of Li-ion batteries. On both a volumetric and gravimetric basis they have higher theoretical capacity than intercalation cathode materials. Metal fluoride (MFx) cathodes offer higher specific energy density and dramatically higher volumetric energy density. Challenges associated with metal fluoride cathodes were addressed through nanostructured material design and synthesis. A major goal of this project was to develop and demonstrate Li-ion cells based on Si-comprising anodes and metal fluoride (MFx) comprising cathodes. Pairing the high-capacity MFx cathode with a high-capacity anode, such as an alloying Si anode, allows for the highest possible energy density on a cell level. After facing and overcoming multiple material synthesis and electrochemical instability challenges, we succeeded in fabrication of MFx half cells with cycle stability in excess of 500 cycles (to 20% or smaller degradation) and full cells with MFx-based cathodes and Si-based anodes with cycle stability in excess of 200 cycles (to 20% or smaller degradation).

  18. The effects of electrospun substrate-mediated cell colony morphology on the self-renewal of human induced pluripotent stem cells.

    Science.gov (United States)

    Maldonado, Maricela; Wong, Lauren Y; Echeverria, Cristina; Ico, Gerardo; Low, Karen; Fujimoto, Taylor; Johnson, Jed K; Nam, Jin

    2015-05-01

    The development of xeno-free, chemically defined stem cell culture systems has been a primary focus in the field of regenerative medicine to enhance the clinical application of pluripotent stem cells (PSCs). In this regard, various electrospun substrates with diverse physiochemical properties were synthesized utilizing various polymer precursors and surface treatments. Human induced pluripotent stem cells (IPSCs) cultured on these substrates were characterized by their gene and protein expression to determine the effects of the substrate physiochemical properties on the cells' self-renewal, i.e., proliferation and the maintenance of pluripotency. The results showed that surface chemistry significantly affected cell colony formation via governing the colony edge propagation. More importantly, when surface chemistry of the substrates was uniformly controlled by collagen conjugation, the stiffness of substrate was inversely related to the sphericity, a degree of three dimensionality in colony morphology. The differences in sphericity subsequently affected spontaneous differentiation of IPSCs during a long-term culture, implicating that the colony morphology is a deciding factor in the lineage commitment of PSCs. Overall, we show that the capability of controlling IPSC colony morphology by electrospun substrates provides a means to modulate IPSC self-renewal. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. JMJD1C Ensures Mouse Embryonic Stem Cell Self-Renewal and Somatic Cell Reprogramming through Controlling MicroRNA Expression.

    Science.gov (United States)

    Xiao, Feng; Liao, Bing; Hu, Jing; Li, Shuang; Zhao, Haixin; Sun, Ming; Gu, Junjie; Jin, Ying

    2017-09-12

    The roles of histone demethylases (HDMs) for the establishment and maintenance of pluripotency are incompletely characterized. Here, we show that JmjC-domain-containing protein 1c (JMJD1C), an H3K9 demethylase, is required for mouse embryonic stem cell (ESC) self-renewal. Depletion of Jmjd1c leads to the activation of ERK/MAPK signaling and epithelial-to-mesenchymal transition (EMT) to induce differentiation of ESCs. Inhibition of ERK/MAPK signaling rescues the differentiation phenotype caused by Jmjd1c depletion. Mechanistically, JMJD1C, with the help of pluripotency factor KLF4, maintains ESC identity at least in part by regulating the expression of the miR-200 family and miR-290/295 cluster to suppress the ERK/MAPK signaling and EMT. Additionally, we uncover that JMJD1C ensures efficient generation and maintenance of induced pluripotent stem cells, at least partially through controlling the expression of microRNAs. Collectively, we propose an integrated model of epigenetic and transcriptional control mediated by the H3K9 demethylase for ESC self-renewal and somatic cell reprogramming. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus

    Science.gov (United States)

    Suh, Hoonkyo; Consiglio, Antonella; Ray, Jasodhara; Sawai, Toru; D'Amour, Kevin A.; Gage, Fred H.

    2007-01-01

    Summary To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate tracing studies showed that Sox2+ cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as a single cell level. More interestingly, a subpopulation of Sox2+ cells gives rise to cells that retain Sox2, highlighting Sox2+ cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2+ cells is coupled with the generation of Sox2+ NSCs as well as neuronal precursors. An asymmetric contribution of Sox2+ NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis. PMID:18371391

  1. Development of high-capacity nickel-metal hydride batteries using superlattice hydrogen-absorbing alloys

    Science.gov (United States)

    Yasuoka, Shigekazu; Magari, Yoshifumi; Murata, Tetsuyuki; Tanaka, Tadayoshi; Ishida, Jun; Nakamura, Hiroshi; Nohma, Toshiyuki; Kihara, Masaru; Baba, Yoshitaka; Teraoka, Hirohito

    New R-Mg-Ni (R: rare earths) superlattice alloys with higher-capacity and higher-durability than the conventional Mm-Ni alloys with CaCu 5 structure have been developed. The oxidation resistibility of the superlattice alloys has been improved by optimizing the alloy composition by such as substituting aluminum for nickel and optimizing the magnesium content in order to prolong the battery life. High-capacity nickel-metal hydride batteries for the retail market, the Ni-MH2500/900 series (AA size type 2500 mAh, AAA size type 900 mAh), have been developed and commercialized by using an improved superlattice alloy for negative electrode material.

  2. Flower-like SnO2/graphene composite for high-capacity lithium storage

    International Nuclear Information System (INIS)

    Liu Hongdong; Huang Jiamu; Li Xinlu; Liu Jia; Zhang Yuxin; Du Kun

    2012-01-01

    Flower-like SnO 2 /graphene composite is synthesized by a simple hydrothermal method for high-capacity lithium storage. The as-prepared products are characterized by XRD, FTIR, FESEM, TGA and Nitrogen adsorption/desorption. The electrochemical performance of the flower-like SnO 2 /graphene composite is measured by cyclic voltammetry and galvanostatic charge/discharge cycling. The results show that the flower-like SnO 2 nanorod clusters are 800 nm in size and homogeneously adhere on graphene sheets. The flower-like SnO 2 /graphene composite displays superior Li-battery performance with large reversible capacity, excellent cyclic performance and good rate capability.

  3. A high capacity text steganography scheme based on LZW compression and color coding

    Directory of Open Access Journals (Sweden)

    Aruna Malik

    2017-02-01

    Full Text Available In this paper, capacity and security issues of text steganography have been considered by employing LZW compression technique and color coding based approach. The proposed technique uses the forward mail platform to hide the secret data. This algorithm first compresses secret data and then hides the compressed secret data into the email addresses and also in the cover message of the email. The secret data bits are embedded in the message (or cover text by making it colored using a color coding table. Experimental results show that the proposed method not only produces a high embedding capacity but also reduces computational complexity. Moreover, the security of the proposed method is significantly improved by employing stego keys. The superiority of the proposed method has been experimentally verified by comparing with recently developed existing techniques.

  4. Development of high-capacity nickel-metal hydride batteries using superlattice hydrogen-absorbing alloys

    International Nuclear Information System (INIS)

    Yasuoka, Shigekazu; Magari, Yoshifumi; Murata, Tetsuyuki; Tanaka, Tadayoshi; Ishida, Jun; Nakamura, Hiroshi; Nohma, Toshiyuki; Kihara, Masaru; Baba, Yoshitaka; Teraoka, Hirohito

    2006-01-01

    New R-Mg-Ni (R: rare earths) superlattice alloys with higher-capacity and higher-durability than the conventional Mm-Ni alloys with CaCu 5 structure have been developed. The oxidation resistibility of the superlattice alloys has been improved by optimizing the alloy composition by such as substituting aluminum for nickel and optimizing the magnesium content in order to prolong the battery life. High-capacity nickel-metal hydride batteries for the retail market, the Ni-MH2500/900 series (AA size type 2500mAh, AAA size type 900mAh), have been developed and commercialized by using an improved superlattice alloy for negative electrode material. alized by using an improved superlattice alloy for negative electrode material. (author)

  5. Atomistic Origins of High Capacity and High Structural Stability of Polymer-Derived SiOC Anode Materials.

    Science.gov (United States)

    Sun, Hong; Zhao, Kejie

    2017-10-11

    Capacity and structural stability are often mutually exclusive properties of electrodes in Li-ion batteries (LIBs): a gain in capacity is usually accompanied by the undesired large volumetric change of the host material upon lithiation. Polymer-derived ceramics, such as silicon oxycarbide (SiOC) of hybrid Si-O-C bonds, show an exceptional combination of high capacity and superior structural stability. We investigate the atomistic origins of the unique chemomechanical performance of carbon-rich SiOC using the first-principles theoretical approach. The atomic model of SiOC is composed of continuous Si-O-C units caged by a graphene-like cellular network and percolated nanovoids. The segregated sp 2 carbon network serves as the backbone to maintain the structural stability of the lattice. Li insertion is first absorbed at the nanovoid sites, and then it is accommodated by the SiOC tetrahedral units, excess C atoms, and topological defects at the edge of or within the segregated carbon network. SiOC expands up to 22% in volumetric strain at the fully lithiated capacity of 1230 mA h/g. We examine in great detail the evolution of the microscopic features of the SiOC molecule in the course of Li reactions. The first-principles modeling provides a fundamental understanding of the physicochemical properties of Si-based glass ceramics for their application in LIBs.

  6. Li2C2, a High-Capacity Cathode Material for Lithium Ion Batteries.

    Science.gov (United States)

    Tian, Na; Gao, Yurui; Li, Yurong; Wang, Zhaoxiang; Song, Xiaoyan; Chen, Liquan

    2016-01-11

    As a typical alkaline earth metal carbide, lithium carbide (Li2C2) has the highest theoretical specific capacity (1400 mA h g(-1)) among all the reported lithium-containing cathode materials for lithium ion batteries. Herein, the feasibility of using Li2C2 as a cathode material was studied. The results show that at least half of the lithium can be extracted from Li2C2 and the reversible specific capacity reaches 700 mA h g(-1). The C≡C bond tends to rotate to form C4 (C≡C⋅⋅⋅C≡C) chains during lithium extraction, as indicated with the first-principles molecular dynamics (FPMD) simulation. The low electronic and ionic conductivity are believed to be responsible for the potential gap between charge and discharge, as is supported with density functional theory (DFT) calculations and Arrhenius fitting results. These findings illustrate the feasibility to use the alkali and alkaline earth metal carbides as high-capacity electrode materials for secondary batteries. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Synthesis of alumina nano-sheets via supercritical fluid technology with high uranyl adsorptive capacity

    International Nuclear Information System (INIS)

    Jing Yu; Jun Wang; Zhanshuang Li; Qi Liu; Milin Zhang; Hongbin Bai; Caishan Jiao; Jun Wang; Lianhe Liu

    2012-01-01

    Supercritical carbon dioxide is beneficial to the synthesis of superior ultrafine and uniform materials due to its high chemical stability, low viscosity, high diffusivity, and 'zero' surface tension. γ-Alumina nano-sheets were obtained by a simple hydrothermal route in the presence of supercritical carbon dioxide. XRD, FTIR, SEM, TEM and nitrogen sorption isotherm were employed to characterize the samples. Alumina as-prepared has a high specific surface area of up to 200 ± 6 m 2 g -1 , which presents a high adsorption capacity (4.66 ± 0.02 mg g -1 ) for uranyl ions from aqueous solution. Furthermore, the adsorption process was found to be endothermic and spontaneous in nature. (authors)

  8. ERP markers of target selection discriminate children with high vs. low working memory capacity

    Directory of Open Access Journals (Sweden)

    Andria eShimi

    2015-11-01

    Full Text Available Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults’ selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children’s selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults’ selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc. However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the adult time-window related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children’s neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM

  9. ERP markers of target selection discriminate children with high vs. low working memory capacity.

    Science.gov (United States)

    Shimi, Andria; Nobre, Anna Christina; Scerif, Gaia

    2015-01-01

    Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM) system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults' selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children's selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults' selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc). However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the "adult time-window" related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children's neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM performance in children.

  10. Peak capacity, peak-capacity production rate, and boiling point resolution for temperature-programmed GC with very high programming rates

    Science.gov (United States)

    Grall; Leonard; Sacks

    2000-02-01

    Recent advances in column heating technology have made possible very fast linear temperature programming for high-speed gas chromatography. A fused-silica capillary column is contained in a tubular metal jacket, which is resistively heated by a precision power supply. With very rapid column heating, the rate of peak-capacity production is significantly enhanced, but the total peak capacity and the boiling-point resolution (minimum boiling-point difference required for the separation of two nonpolar compounds on a nonpolar column) are reduced relative to more conventional heating rates used with convection-oven instruments. As temperature-programming rates increase, elution temperatures also increase with the result that retention may become insignificant prior to elution. This results in inefficient utilization of the down-stream end of the column and causes a loss in the rate of peak-capacity production. The rate of peak-capacity production is increased by the use of shorter columns and higher carrier gas velocities. With high programming rates (100-600 degrees C/min), column lengths of 6-12 m and average linear carrier gas velocities in the 100-150 cm/s range are satisfactory. In this study, the rate of peak-capacity production, the total peak capacity, and the boiling point resolution are determined for C10-C28 n-alkanes using 6-18 m long columns, 50-200 cm/s average carrier gas velocities, and 60-600 degrees C/min programming rates. It was found that with a 6-meter-long, 0.25-mm i.d. column programmed at a rate of 600 degrees C/min, a maximum peak-capacity production rate of 6.1 peaks/s was obtained. A total peak capacity of about 75 peaks was produced in a 37-s long separation spanning a boiling-point range from n-C10 (174 degrees C) to n-C28 (432 degrees C).

  11. Improvements on high voltage capacity and high temperature performances of Si-based Schottky potential barrier diode

    International Nuclear Information System (INIS)

    Wang Yongshun; Rui Li; Adnan Ghaffar; Wang Zaixing; Liu Chunjuan

    2015-01-01

    In order to improve the reverse voltage capacity and low junction temperature characteristics of the traditional silicon-based Schottky diode, a Schottky diode with high reverse voltage capacity and high junction temperature was fabricated using ion implantation, NiPt60 sputtering, silicide-forming and other major technologies on an N-type silicon epitaxial layer of 10.6–11.4 μm and (2.2–2.4) × 10 15 cm −3 doping concentration. The measurement results show that the junction temperature of the Schottky diode fabricated can reach 175 °C, that is 50 °C higher than that of the traditional one; the reverse voltage capacity V R can reach 112 V, that is 80 V higher than that of the traditional one; the leakage current is only 2 μA and the forward conduction voltage drop is V F = 0.71 V at forward current I F = 3 A. (semiconductor devices)

  12. Durability testing of the high-capacity GA-4/GA-9 trailer

    International Nuclear Information System (INIS)

    Zimmer, A.

    1993-01-01

    General Atomics (GA) is under contract to the US Department of Energy (DOE), Idaho Field Office, to develop two legal-weight truck from-reactor spent-fuel shipping casks with trailers. GA is developing these high capacity transport systems to support the Office of Civilian Radioactive Waste Management's (OCRWM) mission to transport spent fuel from reactors to a permanent disposal site. GA's goal is to maximize the number of fuel assemblies that the transport system can safely carry. The GA-4 Cask is being designed to transport four pressurized-water-reactor (PWR) spent-fuel assemblies, and the GA-9 Cask is being designed to transport nine boiling-water-reactor (BWR) spent-fuel assemblies. The use of these high-capacity transport systems will have a large benefit to-public safety since the number of legal-weight truck shipments will be reduced by at least a factor of four over existing spent-fuel shipping cask systems. Achieving these capacities requires that the weight of each component of the transport system. i.e., cask, trailer and tractor, be minimized. The weight of the trailer is of particular importance. With a high load-to-weight ratio, the durability and reliability of the trailer become significant factors in the success of the transport system. In order to verify that the trailer design will meet the durability and performance requirements to safely transport spent-fuel, GA has planned an extensive testing program. The testing program includes non-destructive examination (NDE) of the trailer welds, operational testing, a static load test, an over-the-road performance test, and a test to verify the durability of the trailer up to its 1,000,000-mile design life. Since a prototype cask will not be available for the testing, GA designed and built a dummy payload that simulates the correct weight distribution and approximates the dynamic response of the prototype cask

  13. Core--strategy leading to high reversible hydrogen storage capacity for NaBH4.

    Science.gov (United States)

    Christian, Meganne L; Aguey-Zinsou, Kondo-François

    2012-09-25

    Owing to its high storage capacity (10.8 mass %), sodium borohydride (NaBH(4)) is a promising hydrogen storage material. However, the temperature for hydrogen release is high (>500 °C), and reversibility of the release is unachievable under reasonable conditions. Herein, we demonstrate the potential of a novel strategy leading to high and stable hydrogen absorption/desorption cycling for NaBH(4) under mild pressure conditions (4 MPa). By an antisolvent precipitation method, the size of NaBH(4) particles was restricted to a few nanometers (hydrogen at 400 °C. Further encapsulation of these nanoparticles upon reaction of nickel chloride at their surface allowed the synthesis of a core--shell nanostructure, NaBH(4)@Ni, and this provided a route for (a) the effective nanoconfinement of the melted NaBH(4) core and its dehydrogenation products, and (b) reversibility and fast kinetics owing to short diffusion lengths, the unstable nature of nickel borohydride, and possible modification of reaction paths. Hence at 350 °C, a reversible and steady hydrogen capacity of 5 mass % was achieved for NaBH(4)@Ni; 80% of the hydrogen could be desorbed or absorbed in less than 60 min, and full capacity was reached within 5 h. To the best of our knowledge, this is the first time that such performances have been achieved with NaBH(4). This demonstrates the potential of the strategy in leading to major advancements in the design of effective hydrogen storage materials from pristine borohydrides.

  14. Titanium-decorated graphene for high-capacity hydrogen storage studied by density functional simulations

    International Nuclear Information System (INIS)

    Liu Yali; Ren Ling; He Yao; Cheng Haiping

    2010-01-01

    We present results of density functional theory (DFT) calculations of the adsorption of hydrogen molecules on Ti-decorated graphene. Our results indicate that the binding energies of molecular hydrogen on Ti-decorated graphene can be dramatically enhanced to 0.23-0.60 eV. The hybridization of the Ti 3d orbitals with the H 2 σ and σ* orbitals plays a central role in the enhanced binding. There is also a contribution from the attractive interaction between the surface dipole and the dipole of polarized H 2 . It can be expected that Ti-decorated graphene could be considered as a potential high-capacity hydrogen storage medium.

  15. High-Capacity Quantum Secure Direct Communication Based on Quantum Hyperdense Coding with Hyperentanglement

    International Nuclear Information System (INIS)

    Wang Tie-Jun; Li Tao; Du Fang-Fang; Deng Fu-Guo

    2011-01-01

    We present a quantum hyperdense coding protocol with hyperentanglement in polarization and spatial-mode degrees of freedom of photons first and then give the details for a quantum secure direct communication (QSDC) protocol based on this quantum hyperdense coding protocol. This QSDC protocol has the advantage of having a higher capacity than the quantum communication protocols with a qubit system. Compared with the QSDC protocol based on superdense coding with d-dimensional systems, this QSDC protocol is more feasible as the preparation of a high-dimension quantum system is more difficult than that of a two-level quantum system at present. (general)

  16. Development and Testing of a High Capacity Plasma Chemical Reactor in the Ukraine

    Energy Technology Data Exchange (ETDEWEB)

    Reilly, Raymond W.

    2012-07-30

    This project, Development and Testing of a High Capacity Plasma Chemical Reactor in the Ukraine was established at the Kharkiv Institute of Physics and Technology (KIPT). The associated CRADA was established with Campbell Applied Physics (CAP) located in El Dorado Hills, California. This project extends an earlier project involving both CAP and KIPT conducted under a separate CRADA. The initial project developed the basic Plasma Chemical Reactor (PCR) for generation of ozone gas. This project built upon the technology developed in the first project, greatly enhancing the output of the PCR while also improving reliability and system control.

  17. IL-6, Antioxidant Capacity and Muscle Damage Markers Following High-Intensity Interval Training Protocols

    OpenAIRE

    Cipryan, Lukas

    2017-01-01

    Abstract The aim of this study was to investigate changes of interleukin-6 (IL-6), total antioxidant capacity (TAC) and muscle damage markers (creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH)) in response to three different high-intensity interval training (HIIT) protocols of identical external work. Twelve moderately-trained males participated in the three HIIT trials which consisted of a warm-up, followed by 12 min of 15 s, 30 s or 60 s HIIT sequences with the work/rest ratio...

  18. Loading capacities and failure modes of various reinforced concrete slabs subjected to high-speed loading

    International Nuclear Information System (INIS)

    Saito, H.; Imamura, A.; Takeuchi, M.; Okamoto, S.; Kasai, Y.; Tsubota, H.; Yoshimura, M.

    1993-01-01

    The objective of this study was to clarify experimentally and analytically the loading capacities, deformations and failure modes of various types of reinforced concrete structures subjected to loads applied at various loading rates. Flat slabs, slabs with beams and cylindrical walls were tested under static, low-speed and high-speed loading. Analysis was applied to estimate the test results by the finite element method using a layered shell element. The analysis closely simulated the experimental results until punching shear failure occurred. (author)

  19. High capacity of plant regeneration from callus of interspecific hybrids with cultivated barley (Hordeum vulgare L.)

    DEFF Research Database (Denmark)

    Bagger Jørgensen, Rikke; Jensen, C. J.; Andersen, B.

    1986-01-01

    Callus was induced from hybrids between cultivated barley (Hordeum vulgare L. ssp. vulgare) and ten species of wild barley (Hordeum L.) as well as from one backcross line ((H. lechleri .times. H. vulgare) .times. H. vulgare). Successful callus induction and regeneration of plants were achieved from...... explants of young spikes on the barley medium J 25-8. The capacity for plant regeneration was dependent on the wild parental species. In particular, combinations with four related wild species, viz. H. jubatum, H. roshevitzii, H. lechleri, and H. procerum, regenerated high numbers of plants from calli....

  20. Ambient-temperature high damping capacity in TiPd-based martensitic alloys

    International Nuclear Information System (INIS)

    Xue, Dezhen; Zhou, Yumei; Ding, Xiangdong; Otsuka, Kazuhiro; Lookman, Turab; Sun, Jun; Ren, Xiaobing

    2015-01-01

    Shape memory alloys (SMAs) have attracted considerable attention for their high damping capacities. Here we investigate the damping behavior of Ti 50 (Pd 50−x D x ) SMAs (D=Fe, Co, Mn, V) by dynamic mechanical analysis. We find that these alloys show remarkably similar damping behavior. There exists a sharp damping peak associated with the B2–B19 martensitic transformation and a high damping plateau (Q −1 ~0.02–0.05) over a wide ambient-temperature range (220–420 K) due to the hysteretic twin boundary motion. After doping hydrogen into the above alloys, a new relaxation-type damping peak appears in the martensite phase over 270–360 K. Such a peak is considered to originate from the interaction of hydrogen atoms with twin boundaries and the corresponding damping capacity (Q −1 ~0.05–0.09) is enhanced by roughly twice that of the damping plateau for each alloy. Moreover, the relaxation peaks are at higher temperatures for the TiPd-based alloys (270–370 K) than for the TiNi-based alloys (190–260 K). We discuss the influence of hydrogen diffusion, mobility of twin boundaries and hydrogen–twin boundary interaction on the temperature range of the relaxation peak. Our results suggest that a martensite, with appropriate values for twinning shear and hydrogen doping level, provides a route towards developing high damping SMAs for applications in desired temperature ranges

  1. Endurance capacity of mice selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Meek, Thomas H; Lonquich, Brian P; Hannon, Robert M; Garland, Theodore

    2009-09-15

    Mice from four lines bred for high voluntary wheel activity run approximately 3-fold more revolutions per day and have elevated maximal oxygen consumption during forced treadmill exercise, as compared with four unselected control (C) lines. We hypothesized that these high runner (HR) lines would have greater treadmill endurance-running capacity. Ninety-six mice from generation 49 were familiarized with running on a motorized treadmill for 3 days. On days 4 and 5, mice were given an incremental speed test (starting at 20 m min(-1), increased 1.5 m min(-1) every 2 min) and endurance was measured as the total time or distance run to exhaustion. Blood samples were taken to measure glucose and lactate concentrations at rest during the photophase, during peak nightly wheel running, and immediately following the second endurance test. Individual differences in endurance time were highly repeatable between days (r=0.79), and mice tended to run longer on the second day (paired t-test, Pwheel running and treadmill endurance differed between the sexes, reinforcing previous studies that indicate sex-specific responses to selective breeding. HR mice appear to have a higher endurance capacity than reported in the literature for inbred strains of mice or transgenics intended to enhance endurance.

  2. Enrichments of methanotrophic-heterotrophic cultures with high poly-β-hydroxybutyrate (PHB) accumulation capacities.

    Science.gov (United States)

    Zhang, Tingting; Wang, Xiaowei; Zhou, Jiti; Zhang, Yu

    2018-03-01

    Methanotrophic-heterotrophic communities were selectively enriched from sewage sludge to obtain a mixed culture with high levels of poly-β-hydroxybutyrate (PHB) accumulation capacity from methane. Methane was used as the carbon source, N 2 as sole nitrogen source, and oxygen and Cu content were varied. Copper proved essential for PHB synthesis. All cultures enriched with Cu could accumulate high content of PHB (43.2%-45.9%), while only small amounts of PHB were accumulated by cultures enriched without Cu (11.9%-17.5%). Batch assays revealed that communities grown with Cu and a higher O 2 content synthesized more PHB, which had a wider optimal CH 4 :O 2 range and produced a high PHB content (48.7%) even though in the presence of N 2 . In all methanotrophic-heterotrophic communities, both methanotrophic and heterotrophic populations showed the ability to accumulate PHB. Although methane was added as the sole carbon source, heterotrophs dominated with abundances between 77.2% and 85.6%. All methanotrophs detected belonged to type II genera, which formed stable communities with heterotrophs of different PHB production capacities. Copyright © 2017. Published by Elsevier B.V.

  3. Evaluating the Value of High Spatial Resolution in National Capacity Expansion Models using ReEDS

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, Venkat; Cole, Wesley

    2016-07-18

    This poster is based on the paper of the same name, presented at the IEEE Power & Energy Society General Meeting, July18, 2016. Power sector capacity expansion models (CEMs) have a broad range of spatial resolutions. This paper uses the Regional Energy Deployment System (ReEDS) model, a long-term national scale electric sector CEM, to evaluate the value of high spatial resolution for CEMs. ReEDS models the United States with 134 load balancing areas (BAs) and captures the variability in existing generation parameters, future technology costs, performance, and resource availability using very high spatial resolution data, especially for wind and solar modeled at 356 resource regions. In this paper we perform planning studies at three different spatial resolutions - native resolution (134 BAs), state-level, and NERC region level - and evaluate how results change under different levels of spatial aggregation in terms of renewable capacity deployment and location, associated transmission builds, and system costs. The results are used to ascertain the value of high geographically resolved models in terms of their impact on relative competitiveness among renewable energy resources.

  4. An Aqueous Redox-Flow Battery with High Capacity and Power: The TEMPTMA/MV System.

    Science.gov (United States)

    Janoschka, Tobias; Martin, Norbert; Hager, Martin D; Schubert, Ulrich S

    2016-11-07

    Redox-flow batteries (RFB) can easily store large amounts of electric energy and thereby mitigate the fluctuating output of renewable power plants. They are widely discussed as energy-storage solutions for wind and solar farms to improve the stability of the electrical grid. Most common RFB concepts are based on strongly acidic metal-salt solutions or poorly performing organics. Herein we present a battery which employs the highly soluble N,N,N-2,2,6,6-heptamethylpiperidinyl oxy-4-ammonium chloride (TEMPTMA) and the viologen derivative N,N'-dimethyl-4,4-bipyridinium dichloride (MV) in a simple and safe aqueous solution as redox-active materials. The resulting battery using these electrolyte solutions has capacities of 54 Ah L -1 , giving a total energy density of 38 Wh L -1 at a cell voltage of 1.4 V. With peak current densities of up to 200 mA cm -2 the TEMPTMA/MV system is a suitable candidate for compact high-capacity and high-power applications. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.

    Science.gov (United States)

    You, Qingping; Zhang, Yuping; Zhang, Qingwen; Guo, Junfang; Huang, Weihua; Shi, Shuyun; Chen, Xiaoqin

    2014-08-08

    Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Self-renewal and differentiation capabilities are variable between human embryonic stem cell lines I3, I6 and BG01V

    Directory of Open Access Journals (Sweden)

    Rao Mahendra S

    2009-06-01

    Full Text Available Abstract Background A unique and essential property of embryonic stem cells is the ability to self-renew and differentiate into multiple cell lineages. However, the possible differences in proliferation and differentiation capabilities among independently-derived human embryonic stem cells (hESCs are not well known because of insufficient characterization. To address this question, a side-by-side comparison of 1 the ability to maintain an undifferentiated state and to self-renew under standard conditions; 2 the ability to spontaneously differentiate into three primary embryonic germ lineages in differentiating embryoid bodies; and 3 the responses to directed neural differentiation was made between three NIH registered hES cell lines I3 (TE03, I6 (TE06 and BG01V. Lines I3 and I6 possess normal XX and a normal XY karyotype while BG01V is a variant cell line with an abnormal karyotype derived from the karyotypically normal cell line BG01. Results Using immunocytochemistry, flow cytometry, qRT-PCR and MPSS, we found that all three cell lines actively proliferated and expressed similar "stemness" markers including transcription factors POU5F1/Oct3/4 and NANOG, glycolipids SSEA4 and TRA-1-81, and alkaline phosphatase activity. All cell lines differentiated into three embryonic germ lineages in embryoid bodies and into neural cell lineages when cultured in neural differentiation medium. However, a profound variation in colony morphology, growth rate, BrdU incorporation, and relative abundance of gene expression in undifferentiated and differentiated states of the cell lines was observed. Undifferentiated I3 cells grew significantly slower but their differentiation potential was greater than I6 and BG01V. Under the same neural differentiation-promoting conditions, the ability of each cell line to differentiate into neural progenitors varied. Conclusion Our comparative analysis provides further evidence for similarities and differences between three h

  7. Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion.

    Science.gov (United States)

    Kent, David G; Li, Juan; Tanna, Hinal; Fink, Juergen; Kirschner, Kristina; Pask, Dean C; Silber, Yvonne; Hamilton, Tina L; Sneade, Rachel; Simons, Benjamin D; Green, Anthony R

    2013-01-01

    Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear. In this article, we identify a distinct cellular mechanism operative in stem cells. By using conditional knock-in mice, we show that the HSC defect resulting from expression of heterozygous human JAK2V617F is both quantitative (reduced HSC numbers) and qualitative (lineage biases and reduced self-renewal per HSC). The defect is intrinsic to individual HSCs and their progeny are skewed toward proliferation and differentiation as evidenced by single cell and transplantation assays. Aged JAK2V617F show a more pronounced defect as assessed by transplantation, but mice that transform reacquire competitive self-renewal ability. Quantitative analysis of HSC-derived clones was used to model the fate choices of normal and JAK2-mutant HSCs and indicates that JAK2V617F reduces self-renewal of individual HSCs but leaves progenitor expansion intact. This conclusion is supported by paired daughter cell analyses, which indicate that JAK2-mutant HSCs more often give rise to two differentiated daughter cells. Together these data suggest that acquisition of JAK2V617F alone is insufficient for clonal expansion and disease progression and causes eventual HSC exhaustion. Moreover, our results show that clonal expansion of progenitor cells provides a window in which collaborating mutations can accumulate to drive disease progression. Characterizing the mechanism(s) of JAK2V617F

  8. Amine-Functionalized Amino Acid-based Ionic Liquids as Efficient and High-Capacity Absorbents for CO2

    DEFF Research Database (Denmark)

    Shunmugavel, Saravanamurugan; Kunov-Kruse, Andreas Jonas; Fehrmann, Rasmus

    2014-01-01

    Ionic liquids (ILs) comprised of ammonium cations and anions of naturally occurring amino acids containing an additional amine group (e.g., lysine, histidine, asparagine, and glutamine) were examined as high-capacity absorbents for CO2. An absorption capacity of 2.1 mol CO2 per mol of IL (3.5 mol...

  9. An insect herbivore microbiome with high plant biomass-degrading capacity.

    Directory of Open Access Journals (Sweden)

    Garret Suen

    2010-09-01

    Full Text Available Herbivores can gain indirect access to recalcitrant carbon present in plant cell walls through symbiotic associations with lignocellulolytic microbes. A paradigmatic example is the leaf-cutter ant (Tribe: Attini, which uses fresh leaves to cultivate a fungus for food in specialized gardens. Using a combination of sugar composition analyses, metagenomics, and whole-genome sequencing, we reveal that the fungus garden microbiome of leaf-cutter ants is composed of a diverse community of bacteria with high plant biomass-degrading capacity. Comparison of this microbiome's predicted carbohydrate-degrading enzyme profile with other metagenomes shows closest similarity to the bovine rumen, indicating evolutionary convergence of plant biomass degrading potential between two important herbivorous animals. Genomic and physiological characterization of two dominant bacteria in the fungus garden microbiome provides evidence of their capacity to degrade cellulose. Given the recent interest in cellulosic biofuels, understanding how large-scale and rapid plant biomass degradation occurs in a highly evolved insect herbivore is of particular relevance for bioenergy.

  10. The Effects of High Intensity Interval Training vs Steady State Training on Aerobic and Anaerobic Capacity.

    Science.gov (United States)

    Foster, Carl; Farland, Courtney V; Guidotti, Flavia; Harbin, Michelle; Roberts, Brianna; Schuette, Jeff; Tuuri, Andrew; Doberstein, Scott T; Porcari, John P

    2015-12-01

    High intensity interval training (HIIT) has become an increasingly popular form of exercise due to its potentially large effects on exercise capacity and small time requirement. This study compared the effects of two HIIT protocols vs steady-state training on aerobic and anaerobic capacity following 8-weeks of training. Fifty-five untrained college-aged subjects were randomly assigned to three training groups (3x weekly). Steady-state (n = 19) exercised (cycle ergometer) 20 minutes at 90% of ventilatory threshold (VT). Tabata (n = 21) completed eight intervals of 20s at 170% VO2max/10s rest. Meyer (n = 15) completed 13 sets of 30s (20 min) @ 100% PVO2 max/ 60s recovery, average PO = 90% VT. Each subject did 24 training sessions during 8 weeks. There were significant (p Tabata protocol was significantly less enjoyable (p HIIT protocols are time efficient, they are not superior to conventional exercise training in sedentary young adults. Key pointsSteady state training equivalent to HIIT in untrained studentsMild interval training presents very similar physiologic challenge compared to steady state trainingHIIT (particularly very high intensity variants were less enjoyable than steady state or mild interval trainingEnjoyment of training decreases across the course of an 8 week experimental training program.

  11. E- and W-band high-capacity hybrid fiber-wireless link

    DEFF Research Database (Denmark)

    Vegas Olmos, Juan José; Pang, Xiaodan; Tafur Monroy, Idelfonso

    2014-01-01

    In this paper we summarize the work conducted in our group in the area of E- and W-band optical high-capacity fiber-wireless links. We present performance evaluations of E- and W-band mm-wave signal generation using photonic frequency upconversion employing both VCSELs and ECLs, along with transm...... in mobile backhaul/fronthaul applications, dense distributed antenna systems and fiber-over-radio scenarios.......In this paper we summarize the work conducted in our group in the area of E- and W-band optical high-capacity fiber-wireless links. We present performance evaluations of E- and W-band mm-wave signal generation using photonic frequency upconversion employing both VCSELs and ECLs, along...... with transmission over different type of optical fibers and for a number of values for the wireless link distance. Hybrid wireless-optical links can be composed of mature and resilient technology available off-the-shelf, and provide functionalities that can add value to optical access networks, specifically...

  12. PV Hosting Capacity Analysis and Enhancement Using High Resolution Stochastic Modeling

    Directory of Open Access Journals (Sweden)

    Emilio J. Palacios-Garcia

    2017-09-01

    Full Text Available Reduction of CO2 emissions is a main target in the future smart grid. This goal is boosting the installation of renewable energy resources (RES, as well as a major consumer engagement that seeks for a more efficient utilization of these resources toward the figure of ‘prosumers’. Nevertheless, these resources present an intermittent nature, which requires the presence of an energy storage system and an energy management system (EMS to ensure an uninterrupted power supply. Moreover, network-related issues might arise due to the increasing power of renewable resources installed in the grid, the storage systems also being capable of contributing to the network stability. However, to assess these future scenarios and test the control strategies, a simulation system is needed. The aim of this paper is to analyze the interaction between residential consumers with high penetration of PV generation and distributed storage and the grid by means of a high temporal resolution simulation scenario based on a stochastic residential load model and PV production records. Results of the model are presented for different PV power rates and storage capacities, as well as a two-level charging strategy as a mechanism for increasing the hosting capacity (HC of the network.

  13. An Insect Herbivore Microbiome with High Plant Biomass-Degrading Capacity

    Energy Technology Data Exchange (ETDEWEB)

    Suen, Garret; Barry, Kerrie; Goodwin, Lynne; Scott, Jarrod; Aylward, Frank; Adams, Sandra; Pinto-Tomas, Adrian; Foster, Clifton; Pauly, Markus; Weimer, Paul; Bouffard, Pascal; Li, Lewyn; Osterberger, Jolene; Harkins, Timothy; Slater, Steven; Donohue, Timothy; Currie, Cameron; Tringe, Susannah G.

    2010-09-23

    Herbivores can gain indirect access to recalcitrant carbon present in plant cell walls through symbiotic associations with lignocellulolytic microbes. A paradigmatic example is the leaf-cutter ant (Tribe: Attini), which uses fresh leaves to cultivate a fungus for food in specialized gardens. Using a combination of sugar composition analyses, metagenomics, and whole-genome sequencing, we reveal that the fungus garden microbiome of leaf-cutter ants is composed of a diverse community of bacteria with high plant biomass-degrading capacity. Comparison of this microbiome?s predicted carbohydrate-degrading enzyme profile with other metagenomes shows closest similarity to the bovine rumen, indicating evolutionary convergence of plant biomass degrading potential between two important herbivorous animals. Genomic and physiological characterization of two dominant bacteria in the fungus garden microbiome provides evidence of their capacity to degrade cellulose. Given the recent interest in cellulosic biofuels, understanding how large-scale and rapid plant biomass degradation occurs in a highly evolved insect herbivore is of particular relevance for bioenergy.

  14. High-capacity conductive nanocellulose paper sheets for electrochemically controlled extraction of DNA oligomers.

    Directory of Open Access Journals (Sweden)

    Aamir Razaq

    Full Text Available Highly porous polypyrrole (PPy-nanocellulose paper sheets have been evaluated as inexpensive and disposable electrochemically controlled three-dimensional solid phase extraction materials. The composites, which had a total anion exchange capacity of about 1.1 mol kg(-1, were used for extraction and subsequent release of negatively charged fluorophore tagged DNA oligomers via galvanostatic oxidation and reduction of a 30-50 nm conformal PPy layer on the cellulose substrate. The ion exchange capacity, which was, at least, two orders of magnitude higher than those previously reached in electrochemically controlled extraction, originated from the high surface area (i.e. 80 m(2 g(-1 of the porous composites and the thin PPy layer which ensured excellent access to the ion exchange material. This enabled the extractions to be carried out faster and with better control of the PPy charge than with previously employed approaches. Experiments in equimolar mixtures of (dT(6, (dT(20, and (dT(40 DNA oligomers showed that all oligomers could be extracted, and that the smallest oligomer was preferentially released with an efficiency of up to 40% during the reduction of the PPy layer. These results indicate that the present material is very promising for the development of inexpensive and efficient electrochemically controlled ion-exchange membranes for batch-wise extraction of biomolecules.

  15. Pectins from the albedo of immature lemon fruitlets have high water binding capacity.

    Science.gov (United States)

    Schröder, Roswitha; Clark, Christopher J; Sharrock, Keith; Hallett, Ian C; MacRae, Elspeth A

    2004-04-01

    The white part of citrus peel, the albedo, has a special role in water relations of both fruit and leaves from early on in fruit development. In times of drought, this tissue acts as a water reservoir for juice sacs, seeds and leaves. When water was injected into the albedo, free water was undetectable using magnetic resonance imaging. Microscopy showed tightly packed cells with little intercellular space, and thick cell walls. Cell wall material comprised 21% of the fresh albedo weight, and contained 26.1% galacturonic acid, the main constituent of pectin. From this, we postulated that pectin of the cell wall was responsible for the high water-binding capacity of the immature lemon albedo. Cell wall material was extracted using mild procedures that keep polymers intact, and four pectic fractions were recovered. Of these fractions, the SDS and chelator-soluble fractions showed viscosities ten and twenty times higher than laboratory-grade citrus pectin or the other albedo-derived pectins. The yield of these two pectins represented 28% of the cell walls and 62% of the galacturonic acid content of immature lemon albedo. We concluded that, from viscosity and abundance, these types of pectin account for the high water-binding capacity of this tissue. Compositional analyses showed that the two highly viscous pectic fractions differ in galacturonic acid content, degree of branching and length of side chains from the less viscous albedo-derived pectins. The most striking feature of these highly viscous pectins, however, was their high molecular weight distribution compared to the other pectic fractions.

  16. High capacity argon extraction and purification system. [Suitable for age estimation of rocks

    Energy Technology Data Exchange (ETDEWEB)

    Balogh, K; Morik, Gy [Magyar Tudomanyos Akademia Atommag Kutato Intezete, Debrecen

    1979-01-01

    A high capacity metal-glass argon extraction and purification system has been developed for K/Ar dating of geologic materials. A set of samples can be loaded simultaneously and degassed in turn in the system by high frequency induction heating in a molybdenum crucible. The argon purification is carried out by titanium sponge, molecular sieve, copper oxide and glass and charcoal filled traps cooled by liquid nitrogen. The /sup 38/Ar spike and the atmospheric argon used for calibrating the mass spectrometer are dispensed by a gas-pipette system. 80-120 minutes after starting the degassing of the sample, the purified argon can be introduced into the mass spectrometer; the gettering materials regenerate in 1-5 hours, thus 1-3 samples may be analysed a day. The atmospheric argon inflow during an experimental process is less than 5x10/sup -8/ cc STP.

  17. An FDMA system concept for 30/20 GHz high capacity domestic satellite service

    Science.gov (United States)

    Berk, G.; Jean, P. N.; Rotholz, E.; White, B. E.

    1982-01-01

    The paper summarizes a feasibility study of a multibeam FDMA satellite system operating in the 30/20 GHz band. The system must accommodate a very high volume of traffic within the restrictions of a 5 kW solar cell array and a 2.5 GHz bandwidth. Multibeam satellite operation reduces the DC power demand and allows reuse of the available bandwidth. Interferences among the beams are brought to acceptable levels by appropriate frequency assignments. A transponder design is presented; it is greatly simplified by the application of a regional concept. System analysis shows that MSK modulation is appropriate for a high-capacity system because it conserves the frequency spectrum. Rain attenuation, a serious problem in this frequency band, is combatted with sufficient power margins and with coding. Link budgets, cost analysis, and weight and power calculations are also discussed. A satellite-routed FDMA system compares favorably in performance and cost with a satellite-switched TDMA system.

  18. Porous carbon with small mesoporesas an ultra-high capacity adsorption medium

    Science.gov (United States)

    Gao, Biaofeng; Zhou, Haitao; Chen, De; Yang, Jianhong

    2017-10-01

    Resins (732-type), abundant and inexpensive resources were used to prepare porous carbon with small mesopores (CSM) by carbonization and post-chemical-activation with potassium hydroxide (KOH). The N2 adsorption measurements revealed that CSM had high surface areas (1776.5 m2 g-1), large pore volumes (1.10 cm3 g-1), and nearly optimal narrow small mesopore sizes ranging from 2 to 7 nm. CSM was used as adsorbent to investigate the adsorption behavior for Rhodamine B (RhB). Due to the optimal pore size distributions (PSD), intensive-stacking interaction, S-doped, and electrostatic attraction, the CSM exhibited an ultra-high-capacity of 1590 mg g-1 for RhB in aqueous solutions.

  19. Sodium bicarbonate and high-intensity-cycling capacity: variability in responses.

    Science.gov (United States)

    Saunders, Bryan; Sale, Craig; Harris, Roger C; Sunderland, Caroline

    2014-07-01

    To determine whether gastrointestinal (GI) distress affects the ergogenicity of sodium bicarbonate and whether the degree of alkalemia or other metabolic responses is different between individuals who improve exercise capacity and those who do not. Twenty-one men completed 2 cycling-capacity tests at 110% of maximum power output. Participants were supplemented with 0.3 g/kg body mass of either placebo (maltodextrin) or sodium bicarbonate (SB). Blood pH, bicarbonate, base excess, and lactate were determined at baseline, preexercise, immediately postexercise, and 5 min postexercise. SB supplementation did not significantly increase total work done (TWD; P = .16, 46.8 ± 9.1 vs 45.6 ± 8.4 kJ, d = 0.14), although magnitude-based inferences suggested a 63% likelihood of a positive effect. When data were analyzed without 4 participants who experienced GI discomfort, TWD (P = .01) was significantly improved with SB. Immediately postexercise blood lactate was higher in SB for the individuals who improved but not for those who did not. There were also differences in the preexercise-to-postexercise change in blood pH, bicarbonate, and base excess between individuals who improved and those who did not. SB improved high-intensity-cycling capacity but only with the exclusion of participants experiencing GI discomfort. Differences in blood responses suggest that SB may not be beneficial to all individuals. Magnitude-based inferences suggested that the exercise effects are unlikely to be negative; therefore, individuals should determine whether they respond well to SB supplementation before competition.

  20. Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells.

    Science.gov (United States)

    Hayashi, Yohei; Caboni, Laura; Das, Debanu; Yumoto, Fumiaki; Clayton, Thomas; Deller, Marc C; Nguyen, Phuong; Farr, Carol L; Chiu, Hsiu-Ju; Miller, Mitchell D; Elsliger, Marc-André; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Tomoda, Kiichiro; Conklin, Bruce R; Wilson, Ian A; Yamanaka, Shinya; Fletterick, Robert J

    2015-04-14

    NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its structural analysis are poorly understood. Here we determined the crystal structure of the human NANOG homeodomain (hNANOG HD) bound to an OCT4 promoter DNA, which revealed amino acid residues involved in DNA recognition that are likely to be functionally important. We generated a series of hNANOG HD alanine substitution mutants based on the protein-DNA interaction and evolutionary conservation and determined their biological activities. Some mutant proteins were less stable, resulting in loss or decreased affinity for DNA binding. Overexpression of the orthologous mouse NANOG (mNANOG) mutants failed to maintain self-renewal of mouse embryonic stem cells without leukemia inhibitory factor. These results suggest that these residues are critical for NANOG transcriptional activity. Interestingly, one mutant, hNANOG L122A, conversely enhanced protein stability and DNA-binding affinity. The mNANOG L122A, when overexpressed in mouse embryonic stem cells, maintained their expression of self-renewal markers even when retinoic acid was added to forcibly drive differentiation. When overexpressed in epiblast stem cells or human induced pluripotent stem cells, the L122A mutants enhanced reprogramming into ground-state pluripotency. These findings demonstrate that structural and biophysical information on key transcriptional factors provides insights into the manipulation of stem cell behaviors and a framework for rational protein engineering.

  1. An important role for adenine, cholera toxin, hydrocortisone and triiodothyronine in the proliferation, self-renewal and differentiation of limbal stem cells in vitro.

    Science.gov (United States)

    Yu, Min; Bojic, Sanja; Figueiredo, Gustavo S; Rooney, Paul; de Havilland, Julian; Dickinson, Anne; Figueiredo, Francisco C; Lako, Majlinda

    2016-11-01

    The cornea is a self-renewing tissue located at the front of the eye. Its transparency is essential for allowing light to focus onto the retina for visual perception. The continuous renewal of corneal epithelium is supported by limbal stem cells (LSCs) which are located in the border region between conjunctiva and cornea known as the limbus. Ex vivo expansion of LSCs has been successfully applied in the last two decades to treat patients with limbal stem cell deficiency (LSCD). Various methods have been used for their expansion, yet the most widely used culture media contains a number of ingredients derived from animal sources which may compromise the safety profile of human LSC transplantation. In this study we sought to understand the role of these components namely adenine, cholera toxin, hydrocortisone and triiodothyronine with the aim of re-defining a safe and GMP compatible minimal media for the ex vivo expansion of LSCs on human amniotic membrane. Our data suggest that all four components play a critical role in maintaining LSC proliferation and promoting LSC self-renewal. However removal of adenine and triiodothyronine had a more profound impact and led to LSC differentiation and loss of viability respectively, suggesting their essential role for ex vivo expansion of LSCs. Replacement of each of the components with GMP-grade reagents resulted in equal growth to non-GMP grade media, however an enhanced differentiation of LSCs was observed, suggesting that additional combinations of GMP grade reagents need to be tested to achieve similar or better level of LSC maintenance in the same manner as the traditional LSC media. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  2. CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of protein-encoding gene and long intergenic non-coding RNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yongyan [College of Veterinary Medicine, Northwest A and F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling 712100, Shaanxi (China); Ai, Zhiying [Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling 712100, Shaanxi (China); College of Life Sciences, Northwest A and F University, Yangling 712100, Shaanxi (China); Yao, Kezhen [College of Veterinary Medicine, Northwest A and F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling 712100, Shaanxi (China); Cao, Lixia; Du, Juan; Shi, Xiaoyan [Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling 712100, Shaanxi (China); College of Life Sciences, Northwest A and F University, Yangling 712100, Shaanxi (China); Guo, Zekun, E-mail: gzk@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A and F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling 712100, Shaanxi (China); Zhang, Yong, E-mail: zhylab@hotmail.com [College of Veterinary Medicine, Northwest A and F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A and F University, Yangling 712100, Shaanxi (China)

    2013-10-15

    Embryonic stem cells (ESCs) can proliferate indefinitely in vitro and differentiate into cells of all three germ layers. These unique properties make them exceptionally valuable for drug discovery and regenerative medicine. However, the practical application of ESCs is limited because it is difficult to derive and culture ESCs. It has been demonstrated that CHIR99021 (CHIR) promotes self-renewal and enhances the derivation efficiency of mouse (m)ESCs. However, the downstream targets of CHIR are not fully understood. In this study, we identified CHIR-regulated genes in mESCs using microarray analysis. Our microarray data demonstrated that CHIR not only influenced the Wnt/β-catenin pathway by stabilizing β-catenin, but also modulated several other pluripotency-related signaling pathways such as TGF-β, Notch and MAPK signaling pathways. More detailed analysis demonstrated that CHIR inhibited Nodal signaling, while activating bone morphogenetic protein signaling in mESCs. In addition, we found that pluripotency-maintaining transcription factors were up-regulated by CHIR, while several developmental-related genes were down-regulated. Furthermore, we found that CHIR altered the expression of epigenetic regulatory genes and long intergenic non-coding RNAs. Quantitative real-time PCR results were consistent with microarray data, suggesting that CHIR alters the expression pattern of protein-encoding genes (especially transcription factors), epigenetic regulatory genes and non-coding RNAs to establish a relatively stable pluripotency-maintaining network. - Highlights: • Combined use of CHIR with LIF promotes self-renewal of J1 mESCs. • CHIR-regulated genes are involved in multiple pathways. • CHIR inhibits Nodal signaling and promotes Bmp4 expression to activate BMP signaling. • Expression of epigenetic regulatory genes and lincRNAs is altered by CHIR.

  3. CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of protein-encoding gene and long intergenic non-coding RNA expression

    International Nuclear Information System (INIS)

    Wu, Yongyan; Ai, Zhiying; Yao, Kezhen; Cao, Lixia; Du, Juan; Shi, Xiaoyan; Guo, Zekun; Zhang, Yong

    2013-01-01

    Embryonic stem cells (ESCs) can proliferate indefinitely in vitro and differentiate into cells of all three germ layers. These unique properties make them exceptionally valuable for drug discovery and regenerative medicine. However, the practical application of ESCs is limited because it is difficult to derive and culture ESCs. It has been demonstrated that CHIR99021 (CHIR) promotes self-renewal and enhances the derivation efficiency of mouse (m)ESCs. However, the downstream targets of CHIR are not fully understood. In this study, we identified CHIR-regulated genes in mESCs using microarray analysis. Our microarray data demonstrated that CHIR not only influenced the Wnt/β-catenin pathway by stabilizing β-catenin, but also modulated several other pluripotency-related signaling pathways such as TGF-β, Notch and MAPK signaling pathways. More detailed analysis demonstrated that CHIR inhibited Nodal signaling, while activating bone morphogenetic protein signaling in mESCs. In addition, we found that pluripotency-maintaining transcription factors were up-regulated by CHIR, while several developmental-related genes were down-regulated. Furthermore, we found that CHIR altered the expression of epigenetic regulatory genes and long intergenic non-coding RNAs. Quantitative real-time PCR results were consistent with microarray data, suggesting that CHIR alters the expression pattern of protein-encoding genes (especially transcription factors), epigenetic regulatory genes and non-coding RNAs to establish a relatively stable pluripotency-maintaining network. - Highlights: • Combined use of CHIR with LIF promotes self-renewal of J1 mESCs. • CHIR-regulated genes are involved in multiple pathways. • CHIR inhibits Nodal signaling and promotes Bmp4 expression to activate BMP signaling. • Expression of epigenetic regulatory genes and lincRNAs is altered by CHIR

  4. Titanium oxynitride thin films as high-capacity and high-rate anode materials for lithium-ion batteries

    International Nuclear Information System (INIS)

    Chiu, Kuo-Feng; Su, Shih-Hsuan; Leu, Hoang-Jyh; Hsia, Chen-Hsien

    2015-01-01

    Titanium oxynitride (TiO_xN_y) was synthesized by reactive magnetron sputtering in a mixed N_2/O_2/Ar gas at ambient temperature. TiO_xN_y thin films with various amounts of nitrogen contents were deposited by varying the N_2/O_2 ratios in the background gas. The synthesized TiO_xN_y films with different compositions (TiO_1_._8_3_7N_0_._0_6_0_, TiO_1_._8_9_0N_0_._0_6_8_, TiO_1_._8_6_5N_0_._0_7_3, and TiO_1_._8_8_2N_0_._1_6_3) all displayed anatase phase, except TiO_1_._8_8_2N_0_._1_6_3. The impedances and grain sizes showed obvious variations with the nitrogen contents. A wide potential window from 3.0 V to 0.05 V, high-rate charge–discharge testing, and long cycle testing were applied to investigate the performances of synthesized TiO_xN_y and pure TiO_2 as anodes for lithium-ion batteries. These TiO_xN_y anodes can be cycled under high rates of 125 μA/cm"2 (10 °C) because of the lower charge–transfer resistance compared with the TiO_2 anode. At 10 °C the discharge capacity of the optimal TiO_xN_y composition is 1.5 times higher than that of pure TiO_2. An unexpectedly large reversible capacity of ~ 300 μAh/cm"2 μm (~ 800 mAh/g) between 1.0 V and 0.05 V was recorded for the TiO_xN_y anodes. The TiO_xN_y anode was cycled (3.0 V to 0.05 V) at 10 °C over 300 times without capacity fading while delivering a capacity of ~ 150 μAh/cm"2 μm (~ 400 mAh/g). - Highlights: • Titanium oxynitride (TiO_xN_y) thin films as anode materials were studied. • TiO_xN_y thin films with various amounts of nitrogen contents were studied_. • High rate capability of TiO_xN_y was studied.

  5. High-capacity quantum secure direct communication with two-photon six-qubit hyperentangled states

    Science.gov (United States)

    Wu, FangZhou; Yang, GuoJian; Wang, HaiBo; Xiong, Jun; Alzahrani, Faris; Hobiny, Aatef; Deng, FuGuo

    2017-12-01

    This study proposes the first high-capacity quantum secure direct communication (QSDC) with two-photon six-qubit hyper-entangled Bell states in two longitudinal momentum and polarization degrees of freedom (DOFs) of photon pairs, which can be generated using two 0.5 mm-thick type-I β barium borate crystal slabs aligned one behind the other and an eight-hole screen. The secret message can be independently encoded on the photon pairs with 64 unitary operations in all three DOFs. This protocol has a higher capacity than previous QSDC protocols because each photon pair can carry 6 bits of information, not just 2 or 4 bits. Our QSDC protocol decreases the influence of decoherence from environment noise by exploiting the decoy photons to check the security of the transmission of the first photon sequence. Compared with two-way QSDC protocols, our QSDC protocol is immune to an attack by an eavesdropper using Trojan horse attack strategies because it is a one-way quantum communication. The QSDC protocol has good applications in the future quantum communication because of all these features.

  6. Carbon Nanofiber/3D Nanoporous Silicon Hybrids as High Capacity Lithium Storage Materials.

    Science.gov (United States)

    Park, Hyeong-Il; Sohn, Myungbeom; Kim, Dae Sik; Park, Cheolho; Choi, Jeong-Hee; Kim, Hansu

    2016-04-21

    Carbon nanofiber (CNF)/3D nanoporous (3DNP) Si hybrid materials were prepared by chemical etching of melt-spun Si/Al-Cu-Fe alloy nanocomposites, followed by carbonization using a pitch. CNFs were successfully grown on the surface of 3DNP Si particles using residual Fe impurities after acidic etching, which acted as a catalyst for the growth of CNFs. The resulting CNF/3DNP Si hybrid materials showed an enhanced cycle performance up to 100 cycles compared to that of the pristine Si/Al-Cu-Fe alloy nanocomposite as well as that of bare 3DNP Si particles. These results indicate that CNFs and the carbon coating layer have a beneficial effect on the capacity retention characteristics of 3DNP Si particles by providing continuous electron-conduction pathways in the electrode during cycling. The approach presented here provides another way to improve the electrochemical performances of porous Si-based high capacity anode materials for lithium-ion batteries. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Fast and simple high-capacity quantum cryptography with error detection

    Science.gov (United States)

    Lai, Hong; Luo, Ming-Xing; Pieprzyk, Josef; Zhang, Jun; Pan, Lei; Li, Shudong; Orgun, Mehmet A.

    2017-04-01

    Quantum cryptography is commonly used to generate fresh secure keys with quantum signal transmission for instant use between two parties. However, research shows that the relatively low key generation rate hinders its practical use where a symmetric cryptography component consumes the shared key. That is, the security of the symmetric cryptography demands frequent rate of key updates, which leads to a higher consumption of the internal one-time-pad communication bandwidth, since it requires the length of the key to be as long as that of the secret. In order to alleviate these issues, we develop a matrix algorithm for fast and simple high-capacity quantum cryptography. Our scheme can achieve secure private communication with fresh keys generated from Fibonacci- and Lucas- valued orbital angular momentum (OAM) states for the seed to construct recursive Fibonacci and Lucas matrices. Moreover, the proposed matrix algorithm for quantum cryptography can ultimately be simplified to matrix multiplication, which is implemented and optimized in modern computers. Most importantly, considerably information capacity can be improved effectively and efficiently by the recursive property of Fibonacci and Lucas matrices, thereby avoiding the restriction of physical conditions, such as the communication bandwidth.

  8. High capacity for extracellular acid-base regulation in the air-breathing fish Pangasianodon hypophthalmus.

    Science.gov (United States)

    Damsgaard, Christian; Gam, Le Thi Hong; Tuong, Dang Diem; Thinh, Phan Vinh; Huong Thanh, Do Thi; Wang, Tobias; Bayley, Mark

    2015-05-01

    The evolution of accessory air-breathing structures is typically associated with reduction of the gills, although branchial ion transport remains pivotal for acid-base and ion regulation. Therefore, air-breathing fishes are believed to have a low capacity for extracellular pH regulation during a respiratory acidosis. In the present study, we investigated acid-base regulation during hypercapnia in the air-breathing fish Pangasianodon hypophthalmus in normoxic and hypoxic water at 28-30°C. Contrary to previous studies, we show that this air-breathing fish has a pronounced ability to regulate extracellular pH (pHe) during hypercapnia, with complete metabolic compensation of pHe within 72 h of exposure to hypoxic hypercapnia with CO2 levels above 34 mmHg. The high capacity for pHe regulation relies on a pronounced ability to increase levels of HCO3(-) in the plasma. Our study illustrates the diversity in the physiology of air-breathing fishes, such that generalizations across phylogenies may be difficult. © 2015. Published by The Company of Biologists Ltd.

  9. Fast and simple high-capacity quantum cryptography with error detection.

    Science.gov (United States)

    Lai, Hong; Luo, Ming-Xing; Pieprzyk, Josef; Zhang, Jun; Pan, Lei; Li, Shudong; Orgun, Mehmet A

    2017-04-13

    Quantum cryptography is commonly used to generate fresh secure keys with quantum signal transmission for instant use between two parties. However, research shows that the relatively low key generation rate hinders its practical use where a symmetric cryptography component consumes the shared key. That is, the security of the symmetric cryptography demands frequent rate of key updates, which leads to a higher consumption of the internal one-time-pad communication bandwidth, since it requires the length of the key to be as long as that of the secret. In order to alleviate these issues, we develop a matrix algorithm for fast and simple high-capacity quantum cryptography. Our scheme can achieve secure private communication with fresh keys generated from Fibonacci- and Lucas- valued orbital angular momentum (OAM) states for the seed to construct recursive Fibonacci and Lucas matrices. Moreover, the proposed matrix algorithm for quantum cryptography can ultimately be simplified to matrix multiplication, which is implemented and optimized in modern computers. Most importantly, considerably information capacity can be improved effectively and efficiently by the recursive property of Fibonacci and Lucas matrices, thereby avoiding the restriction of physical conditions, such as the communication bandwidth.

  10. When high working memory capacity is and is not beneficial for predicting nonlinear processes.

    Science.gov (United States)

    Fischer, Helen; Holt, Daniel V

    2017-04-01

    Predicting the development of dynamic processes is vital in many areas of life. Previous findings are inconclusive as to whether higher working memory capacity (WMC) is always associated with using more accurate prediction strategies, or whether higher WMC can also be associated with using overly complex strategies that do not improve accuracy. In this study, participants predicted a range of systematically varied nonlinear processes based on exponential functions where prediction accuracy could or could not be enhanced using well-calibrated rules. Results indicate that higher WMC participants seem to rely more on well-calibrated strategies, leading to more accurate predictions for processes with highly nonlinear trajectories in the prediction region. Predictions of lower WMC participants, in contrast, point toward an increased use of simple exemplar-based prediction strategies, which perform just as well as more complex strategies when the prediction region is approximately linear. These results imply that with respect to predicting dynamic processes, working memory capacity limits are not generally a strength or a weakness, but that this depends on the process to be predicted.

  11. The Effects of High Intensity Interval Training vs Steady State Training on Aerobic and Anaerobic Capacity

    Directory of Open Access Journals (Sweden)

    Carl Foster, Courtney V. Farland, Flavia Guidotti, Michelle Harbin, Brianna Roberts, Jeff Schuette, Andrew Tuuri, Scott T. Doberstein, John P. Porcari

    2015-12-01

    Full Text Available High intensity interval training (HIIT has become an increasingly popular form of exercise due to its potentially large effects on exercise capacity and small time requirement. This study compared the effects of two HIIT protocols vs steady-state training on aerobic and anaerobic capacity following 8-weeks of training. Fifty-five untrained college-aged subjects were randomly assigned to three training groups (3x weekly. Steady-state (n = 19 exercised (cycle ergometer 20 minutes at 90% of ventilatory threshold (VT. Tabata (n = 21 completed eight intervals of 20s at 170% VO2max/10s rest. Meyer (n = 15 completed 13 sets of 30s (20 min @ 100% PVO2 max/ 60s recovery, average PO = 90% VT. Each subject did 24 training sessions during 8 weeks. Results: There were significant (p < 0.05 increases in VO2max (+19, +18 and +18% and PPO (+17, +24 and +14% for each training group, as well as significant increases in peak (+8, + 9 and +5% & mean (+4, +7 and +6% power during Wingate testing, but no significant differences between groups. Measures of the enjoyment of the training program indicated that the Tabata protocol was significantly less enjoyable (p < 0.05 than the steady state and Meyer protocols, and that the enjoyment of all protocols declined (p < 0.05 across the duration of the study. The results suggest that although HIIT protocols are time efficient, they are not superior to conventional exercise training in sedentary young adults.

  12. Hierarchically structured lithium titanate for ultrafast charging in long-life high capacity batteries

    Science.gov (United States)

    Odziomek, Mateusz; Chaput, Frédéric; Rutkowska, Anna; Świerczek, Konrad; Olszewska, Danuta; Sitarz, Maciej; Lerouge, Frédéric; Parola, Stephane

    2017-05-01

    High-performance Li-ion batteries require materials with well-designed and controlled structures on nanometre and micrometre scales. Electrochemical properties can be enhanced by reducing crystallite size and by manipulating structure and morphology. Here we show a method for preparing hierarchically structured Li4Ti5O12 yielding nano- and microstructure well-suited for use in lithium-ion batteries. Scalable glycothermal synthesis yields well-crystallized primary 4-8 nm nanoparticles, assembled into porous secondary particles. X-ray photoelectron spectroscopy reveals presence of Ti+4 only; combined with chemical analysis showing lithium deficiency, this suggests oxygen non-stoichiometry. Electron microscopy confirms hierarchical morphology of the obtained material. Extended cycling tests in half cells demonstrates capacity of 170 mAh g-1 and no sign of capacity fading after 1,000 cycles at 50C rate (charging completed in 72 s). The particular combination of nanostructure, microstructure and non-stoichiometry for the prepared lithium titanate is believed to underlie the observed electrochemical performance of material.

  13. SDN control of optical nodes in metro networks for high capacity inter-datacentre links

    Science.gov (United States)

    Magalhães, Eduardo; Perry, Philip; Barry, Liam

    2017-11-01

    Worldwide demand for bandwidth has been growing fast for some years and continues to do so. To cover this, mega datacentres need scalable connectivity to provide rich connectivity to handle the heavy traffic across them. Therefore, hardware infrastructures must be able to play different roles according to service and traffic requirements. In this context, software defined networking (SDN) decouples the network control and forwarding functions enabling the network control to become directly programmable and the underlying infrastructure to be abstracted for applications and network services. In addition, elastic optical networking (EON) technologies enable efficient spectrum utilization by allocating variable bandwidth to each user according to their actual needs. In particular, flexible transponders and reconfigurable optical add/drop multiplexers (ROADMs) are key elements since they can offer degrees of freedom to self adapt accordingly. Thus, it is crucial to design control methods in order to optimize the hardware utilization and offer high reconfigurability, flexibility and adaptability. In this paper, we propose and analyze, using a simulation framework, a method of capacity maximization through optical power profile manipulation for inter datacentre links that use existing metropolitan optical networks by exploiting the global network view afforded by SDN. Results show that manipulating the loss profiles of the ROADMs in the metro-network can yield optical signal-to-noise ratio (OSNR) improvements up to 10 dB leading to an increase in 112% in total capacity.

  14. Ambient-temperature high damping capacity in TiPd-based martensitic alloys

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Dezhen [Multi-disciplinary Materials Research Center, Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Zhou, Yumei, E-mail: zhouyumei@mail.xjtu.edu.cn [Multi-disciplinary Materials Research Center, Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Ding, Xiangdong [Multi-disciplinary Materials Research Center, Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Otsuka, Kazuhiro [Ferroic Physics Group, National Institute for Materials Science, Tsukuba 305-0047, Ibaraki (Japan); Lookman, Turab [Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Sun, Jun [Multi-disciplinary Materials Research Center, Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Ren, Xiaobing [Multi-disciplinary Materials Research Center, Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Ferroic Physics Group, National Institute for Materials Science, Tsukuba 305-0047, Ibaraki (Japan)

    2015-04-24

    Shape memory alloys (SMAs) have attracted considerable attention for their high damping capacities. Here we investigate the damping behavior of Ti{sub 50}(Pd{sub 50−x}D{sub x}) SMAs (D=Fe, Co, Mn, V) by dynamic mechanical analysis. We find that these alloys show remarkably similar damping behavior. There exists a sharp damping peak associated with the B2–B19 martensitic transformation and a high damping plateau (Q{sup −1}~0.02–0.05) over a wide ambient-temperature range (220–420 K) due to the hysteretic twin boundary motion. After doping hydrogen into the above alloys, a new relaxation-type damping peak appears in the martensite phase over 270–360 K. Such a peak is considered to originate from the interaction of hydrogen atoms with twin boundaries and the corresponding damping capacity (Q{sup −1}~0.05–0.09) is enhanced by roughly twice that of the damping plateau for each alloy. Moreover, the relaxation peaks are at higher temperatures for the TiPd-based alloys (270–370 K) than for the TiNi-based alloys (190–260 K). We discuss the influence of hydrogen diffusion, mobility of twin boundaries and hydrogen–twin boundary interaction on the temperature range of the relaxation peak. Our results suggest that a martensite, with appropriate values for twinning shear and hydrogen doping level, provides a route towards developing high damping SMAs for applications in desired temperature ranges.

  15. Highly Porous Silicon Embedded in a Ceramic Matrix: A Stable High-Capacity Electrode for Li-Ion Batteries.

    Science.gov (United States)

    Vrankovic, Dragoljub; Graczyk-Zajac, Magdalena; Kalcher, Constanze; Rohrer, Jochen; Becker, Malin; Stabler, Christina; Trykowski, Grzegorz; Albe, Karsten; Riedel, Ralf

    2017-11-28

    We demonstrate a cost-effective synthesis route that provides Si-based anode materials with capacities between 2000 and 3000 mAh·g Si -1 (400 and 600 mAh·g composite -1 ), Coulombic efficiencies above 99.5%, and almost 100% capacity retention over more than 100 cycles. The Si-based composite is prepared from highly porous silicon (obtained by reduction of silica) by encapsulation in an organic carbon and polymer-derived silicon oxycarbide (C/SiOC) matrix. Molecular dynamics simulations show that the highly porous silicon morphology delivers free volume for the accommodation of strain leading to no macroscopic changes during initial Li-Si alloying. In addition, a carbon layer provides an electrical contact, whereas the SiOC matrix significantly diminishes the interface between the electrolyte and the electrode material and thus suppresses the formation of a solid-electrolyte interphase on Si. Electrochemical tests of the micrometer-sized, glass-fiber-derived silicon demonstrate the up-scaling potential of the presented approach.

  16. Extremely High Phosphate Sorption Capacity in Cu-Pb-Zn Mine Tailings.

    Science.gov (United States)

    Huang, Longbin; Li, Xiaofang; Nguyen, Tuan A H

    2015-01-01

    Elevated inorganic phosphate (Pi) concentrations in pore water of amended tailings under direct revegetation may cause toxicity in some native woody species but not native forbs or herb species, all of which are key constituents in target native plant communities for phytostabilizing base metal mine tailings. As a result, Pi sorption capacity has been quantified by a conventional batch procedure in three types of base metal mine tailings sampled from two copper (Cu)-lead (Pb)-zinc (Zn) mines, as the basis for Pi-fertiliser addition. It was found that the Pi-sorption capacity in the tailings and local soil was extremely high, far higher than highly weathered agricultural soils in literature, but similar to those of volcanic ash soils. The Langmuir P-sorption maximum was up to 7.72, 4.12, 4.02 and 3.62 mg P g-1 tailings, in the fresh tailings of mixed Cu-Pb-Zn streams (MIMTD7), the weathered tailings of mixed Cu-Pb-Zn streams (MIMTD5), EHM-TD (fresh Cu-stream, high magnetite content) and local soil (weathered shale and schist), respectively. Physicochemical factors highly correlated with the high Pi-sorption in the tailings were fine particle distribution, oxalate and dithionite-citrate-bicarbonate extractable Fe (FeO and Fed), oxalate-extractable Al and Mn, and the levels of soluble Cd and Zn, and total S and Fe. Large amounts of amorphous Fe oxides and oxyhydroxides may have been formed from the oxidation of pyritic materials and redox cycles of Fe-minerals (such as pyrite (FeS2), ankerite (Ca(Fe Mg)(CO3)2 and siderite (FeCO3), as indicated by the extractable FeO values. The likely formation of sparingly soluble Zn-phosphate in the Pb-Zn tailings containing high levels of Zn (from sphalerite ((Zn,Fe)S, ZnS, (Zn,Cd)S)) may substantially lower soluble Zn levels in the tailings through high rates of Pi-fertiliser addition. As a result, the possibility of P-toxicity in native plant species caused by the addition of soluble phosphate fertilizers would be minimal.

  17. Extremely High Phosphate Sorption Capacity in Cu-Pb-Zn Mine Tailings.

    Directory of Open Access Journals (Sweden)

    Longbin Huang

    Full Text Available Elevated inorganic phosphate (Pi concentrations in pore water of amended tailings under direct revegetation may cause toxicity in some native woody species but not native forbs or herb species, all of which are key constituents in target native plant communities for phytostabilizing base metal mine tailings. As a result, Pi sorption capacity has been quantified by a conventional batch procedure in three types of base metal mine tailings sampled from two copper (Cu-lead (Pb-zinc (Zn mines, as the basis for Pi-fertiliser addition. It was found that the Pi-sorption capacity in the tailings and local soil was extremely high, far higher than highly weathered agricultural soils in literature, but similar to those of volcanic ash soils. The Langmuir P-sorption maximum was up to 7.72, 4.12, 4.02 and 3.62 mg P g-1 tailings, in the fresh tailings of mixed Cu-Pb-Zn streams (MIMTD7, the weathered tailings of mixed Cu-Pb-Zn streams (MIMTD5, EHM-TD (fresh Cu-stream, high magnetite content and local soil (weathered shale and schist, respectively. Physicochemical factors highly correlated with the high Pi-sorption in the tailings were fine particle distribution, oxalate and dithionite-citrate-bicarbonate extractable Fe (FeO and Fed, oxalate-extractable Al and Mn, and the levels of soluble Cd and Zn, and total S and Fe. Large amounts of amorphous Fe oxides and oxyhydroxides may have been formed from the oxidation of pyritic materials and redox cycles of Fe-minerals (such as pyrite (FeS2, ankerite (Ca(Fe Mg(CO32 and siderite (FeCO3, as indicated by the extractable FeO values. The likely formation of sparingly soluble Zn-phosphate in the Pb-Zn tailings containing high levels of Zn (from sphalerite ((Zn,FeS, ZnS, (Zn,CdS may substantially lower soluble Zn levels in the tailings through high rates of Pi-fertiliser addition. As a result, the possibility of P-toxicity in native plant species caused by the addition of soluble phosphate fertilizers would be minimal.

  18. Design of a Two-stage High-capacity Stirling Cryocooler Operating below 30K

    Science.gov (United States)

    Wang, Xiaotao; Dai, Wei; Zhu, Jian; Chen, Shuai; Li, Haibing; Luo, Ercang

    The high capacity cryocooler working below 30K can find many applications such as superconducting motors, superconducting cables and cryopump. Compared to the GM cryocooler, the Stirling cryocooler can achieve higher efficiency and more compact structure. Because of these obvious advantages, we have designed a two stage free piston Stirling cryocooler system, which is driven by a moving magnet linear compressor with an operating frequency of 40 Hz and a maximum 5 kW input electric power. The first stage of the cryocooler is designed to operate in the liquid nitrogen temperature and output a cooling power of 100 W. And the second stage is expected to simultaneously provide a cooling power of 50 W below the temperature of 30 K. In order to achieve the best system efficiency, a numerical model based on the thermoacoustic model was developed to optimize the system operating and structure parameters.

  19. Lithium decoration of three dimensional boron-doped graphene frameworks for high-capacity hydrogen storage

    International Nuclear Information System (INIS)

    Wang, Yunhui; Meng, Zhaoshun; Liu, Yuzhen; You, Dongsen; Wu, Kai; Lv, Jinchao; Wang, Xuezheng; Deng, Kaiming; Lu, Ruifeng; Rao, Dewei

    2015-01-01

    Based on density functional theory and the first principles molecular dynamics simulations, a three-dimensional B-doped graphene-interconnected framework has been constructed that shows good thermal stability even after metal loading. The average binding energy of adsorbed Li atoms on the proposed material (2.64 eV) is considerably larger than the cohesive energy per atom of bulk Li metal (1.60 eV). This value is ideal for atomically dispersed Li doping in experiments. From grand canonical Monte Carlo simulations, high hydrogen storage capacities of 5.9 wt% and 52.6 g/L in the Li-decorated material are attained at 298 K and 100 bars

  20. High-intensity resistance and cardiovascular training improve physical capacity in cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Quist, Morten; Rørth, Mikael Rahbek; Zacho, Morten

    2006-01-01

    The purpose of the study was to examine the effects of a supervised high- and low-intensity structured training program in cancer patients concurrently undergoing chemotherapy. Seventy patients, in different stages of the disease and with different diagnoses (48 females, 22 males), between 18...... and 65 years of age (mean age 42.8) participated in a 9-h weekly training program over 6 weeks. The intervention involved physical exercise, relaxation, massage, and body-awareness training. Physical capacity (one-repetition maximum tests (1RM), VO2max) and body composition (weight, skin-fold) were......-term study support the theory that exercise is a beneficial intervention strategy for increasing muscle strength and aerobic fitness during antineoplastic chemotherapy. This type of exercise program can be an important component of complementary treatment for cancer patients undergoing chemotherapy....

  1. Operating experience with a high capacity helium pump under supercritical conditions

    International Nuclear Information System (INIS)

    Lehmann, W.; Minges, J.

    1984-01-01

    This chapter discusses the development and testing of a high-capacity piston pump to provide forced cooling for large superconducting magnets. The pump is a three cylinder, vertically arranged single-acting piston pump equipped with a frequency controlled three-phase geared motor operating at room temperature. The pump is capable of delivering up to 150 g/s at a maximum speed of 310 rpm and under the inlet conditions of 4 bar/4.5 K. No decline was noticed in delivery head and efficiencies during more than 560 hours of operation. It is concluded that the pump satisfies all requirements for circulating large mass flows across great pressure differences as needed (e.g. in fusion magnet design)

  2. Controlled synthesis of porous anhydrous cobalt oxalate nanorods with high reversible capacity and excellent cycling stability

    International Nuclear Information System (INIS)

    Xu, Junmin; He, Lei; Liu, Hui; Han, Tao; Wang, Yongjian; Zhang, Changjin; Zhang, Yuheng

    2015-01-01

    Graphical abstract: Display Omitted -- Abstract: One-dimensional porous anhydrous cobalt oxalate nanorods are prepared via a facile water-controlled coprecipitate method followed by thermal annealing treatment under N 2 at 300 °C. The nanorods are characterized by using X-ray diffraction, scanning electron microscopy and transmission electron microscopy. When evaluated as an anode material for lithium ion batteries, the nanorods exhibit high reversible specific capacity and excellent cycling stability (924 mA h g −1 at 50 mA g −1 after 100 cycles and 709 mA h g −1 at 200 mA g −1 after 220 cycles). This remarkable electrochemical performance is attributed to the one-dimensional porous nanostructure that can provide large electrode/electrolyte contact area and short lithium-ion diffusion pathway, meanwhile reduce the volume expansion during the repeated discharge/charge process

  3. The anchorage capacity of reinforcing bars at normal and high temperatures

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl

    1982-01-01

    of the cross-section. A simple method for calculating the resistance to splitting is proposed, and a test method for determining the bond strength is presented. Test results are shown from a series of 280 specimens exposed to various maximum temperatures, and a relation between the bond strength......The anchorage failure of reinforcing bars is analysed, and it is shown that two modes of failures are possible: splitting or bond failure. It is concluded that the anchorage capacity cannot be estimated by means of a standard specimen, since splitting failure is dependent upon the geometry...... and the ultimate limit stress of concrete under plane strain conditions is indicated. The influence of high temperatures upon the anchorage resistance is explained, and the theory is illustrated by examples....

  4. Effect of β-alanine plus sodium bicarbonate on high-intensity cycling capacity.

    Science.gov (United States)

    Sale, Craig; Saunders, Bryan; Hudson, Sean; Wise, John A; Harris, Roger C; Sunderland, Caroline D

    2011-10-01

    We examined the effect of β-alanine supplementation plus sodium bicarbonate on high-intensity cycling capacity. Twenty males (age = 25 ± 5 yr, height = 1.79 ± 0.06 m, body mass = 80.0 ± 10.3 kg) were assigned to either a placebo (P) or a β-alanine (BA; 6.4 g·d(-1) for 4 wk) group based on power max, completing four cycling capacity tests at 110% of power max (CCT110%) to determine time to exhaustion (TTE) and total work done. A CCT(110%) was performed twice (habituation and baseline) before supplementation (with maltodextrin [MD]) and twice after supplementation (with MD and with sodium bicarbonate [SB]), using a crossover design with 2 d of rest between trials, creating four study conditions (PMD, PSB, BAMD, and BASB). Blood pH, Lactate, bicarbonate and base excess were determined at baseline, before exercise, immediately after exercise, and 5 min after exercise. Data were analyzed using repeated-measures ANOVA. TTE was increased in all conditions after supplementation (+1.6% PMD, +6.5% PSB, +12.1% BAMD, and +16.2% BASB). Both BAMD and BASB resulted in significantly improved TTE compared with that before supplementation (P ≤ 0.01). Although further increases in TTE (4.1%) were shown in BASB compared with BAMD, these differences were not significant (P = 0.74). Differences in total work done were similar to those of TTE. Blood bicarbonate concentrations were significantly (P ≤ 0.001) elevated before exercise in PSB and BASB but not in PMD or BAMD. Blood lactate concentrations were significantly elevated after exercise, remaining elevated after 5 min of recovery (P ≤ 0.001) and were highest in PSB and BASB. Results show that BA improved high-intensity cycling capacity. However, despite a 6-s (∼4%) increase in TTE with the addition of SB, this did not reach statistical significance, but magnitude-based inferences suggested a ∼70% probability of a meaningful positive difference.

  5. Preparation of surface modified zinc oxide nanoparticle with high capacity dye removal ability

    International Nuclear Information System (INIS)

    Mahmoodi, Niyaz Mohammad; Najafi, Farhood

    2012-01-01

    Highlights: ► Amine-functionalized zinc oxide nanoparticle (AFZON) was synthesized. ► Isotherm and kinetics data followed Langmuir isotherm and pseudo-second order kinetic model, respectively. ► Q 0 of ZON for AB25, DR23 and DR31 was 20, 12 and 15 mg/g, respectively. ► Q 0 of AFZON for AB25, DR23 and DR31 was 1250, 1000 and 1429 mg/g, respectively. ► AFZON was regenerated at pH 12. -- Abstract: In this paper, the surface modification of zinc oxide nanoparticle (ZON) by amine functionalization was studied to prepare high capacity adsorbent. Dye removal ability of amine-functionalized zinc oxide nanoparticle (AFZON) and zinc oxide nanoparticle (ZON) was also investigated. The physical characteristics of AFZON were studied using Fourier transform infrared (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Acid Blue 25 (AB25), Direct Red 23 (DR23) and Direct Red 31 (DR31) were used as model compounds. The effect of operational parameters such as dye concentration, adsorbent dosage, pH and salt on dye removal was evaluated. The isotherm and kinetic of dye adsorption were studied. The maximum dye adsorption capacity (Q 0 ) was 20 mg/g AB25, 12 mg/g DR23 and 15 mg/g DR31 for ZON and 1250 mg/g AB25, 1000 mg/g DR23 and 1429 mg/g DR31 for AFZON. It was found that dye adsorption followed Langmuir isotherm. Adsorption kinetic of dyes was found to conform to pseudo-second order kinetics. Dye desorption tests (adsorbent regeneration) showed that the maximum dye release of 90% AB25, 86% for DR23 and 90% for DR31 were achieved in aqueous solution at pH 12. Based on the data of the present investigation, it can be concluded that the AFZON being an adsorbent with high dye adsorption capacity might be a suitable alternative to remove dyes from colored aqueous solutions.

  6. Final Report: Laboratory Development of a High Capacity Gas-Fired Paper Dryer

    Energy Technology Data Exchange (ETDEWEB)

    Yaroslav Chudnovsky; Aleksandr Kozlov; Lester Sherrow

    2005-09-30

    Paper drying is the most energy-intensive and temperature-critical aspect of papermaking. It is estimated that about 67% of the total energy required in papermaking is used to dry paper. The conventional drying method uses a series of steam-heated metal cylinders that are required to meet ASME codes for pressure vessels, which limits the steam pressure to about 160 psig. Consequently, the shell temperature and the drying capacity are also limited. Gas Technology Institute together with Boise Paper Solutions, Groupe Laperrier and Verreault (GL&V) USA Inc., Flynn Burner Corporation and with funding support from the U.S. Department of Energy, U.S. natural gas industry, and Gas Research Institute is developing a high efficiency gas-fired paper dryer based on a combination of a ribbon burner and advanced heat transfer enhancement technique. The Gas-Fired Paper Dryer (GFPD) is a high-efficiency alternative to conventional steam-heated drying drums that typically operate at surface temperatures in the 300 deg F range. The new approach was evaluated in laboratory and pilot-scale testing at the Western Michigan University Paper Pilot Plant. Drum surface temperatures of more than 400 deg F were reached with linerboard (basis weight 126 lb/3000 ft2) production and resulted in a 4-5 times increase in drying rate over a conventional steam-heated drying drum. Successful GFPD development and commercialization will provide large energy savings to the paper industry and increase paper production rates from dryer-limited (space- or steam-limited) paper machines by an estimated 10 to 20%, resulting in significant capital costs savings for both retrofits and new capacity.

  7. Laboratory Development of A High Capacity Gas-Fired paper Dryer

    Energy Technology Data Exchange (ETDEWEB)

    Chudnovsky, Yaroslav [Gas Technology Institute, Des Plaines, IL (United States); Kozlov, Aleksandr [Gas Technology Institute, Des Plaines, IL (United States); Sherrow, Lester [Gas Technology Institute, Des Plaines, IL (United States)

    2005-09-30

    Paper drying is the most energy-intensive and temperature-critical aspect of papermaking. It is estimated that about 67% of the total energy required in papermaking is used to dry paper. The conventional drying method uses a series of steam-heated metal cylinders that are required to meet ASME codes for pressure vessels, which limits the steam pressure to about 160 psig. Consequently, the shell temperature and the drying capacity are also limited. Gas Technology Institute together with Boise Paper Solutions, Groupe Laparrier and Verreault (GL&V) USA Inc., Flynn Burner Corporation and with funding support from the U.S. Department of Energy, U.S. natural gas industry, and Gas Research Institute is developing a high efficiency gas-fired paper dryer based on a combination of a ribbon burner and advanced heat transfer enhancement technique. The Gas-Fired Paper Dryer (GFPD) is a high-efficiency alternative to conventional steam-heated drying drums that typically operate at surface temperatures in the 300ºF range. The new approach was evaluated in laboratory and pilot-scale testing at the Western Michigan University Paper Pilot Plant. Drum surface temperatures of more than 400ºF were reached with linerboard (basis weight 126 lb/3000 ft2) production and resulted in a 4-5 times increase in drying rate over a conventional steam-heated drying drum. Successful GFPD development and commercialization will provide large energy savings to the paper industry and increase paper production rates from dryer-limited (space- or steam-limited) paper machines by an estimated 10 to 20%, resulting in significant capital costs savings for both retrofits and new capacity.

  8. Evaluation of the radiosensitivity of acute myeloblastic leukaemia progenitor cells by culture methods exploring self-renewal. Evaluation de la radiosensibilite des progeniteurs de leucemie aigue myeloblastique par des methodes de culture explorant ou non l'autorenouvellement

    Energy Technology Data Exchange (ETDEWEB)

    Cowen, D; Richaud, P; Landriau, S; Lagarde, P; Gualde, N [Fondation Bergonie, 33 - Bordeaux (France); Boiron, J M [Hopital du Haut-Leveque, 33 - Pessac (France); Mahon, F X; Belloc, F [Hopital Regional, 33 - Bordeaux (France); Reiffers, J [Hopital du Haut-Leveque, 33 - Pessac (France) Hopital Regional, 33 - Bordeaux (France)

    1993-01-01

    The progenitor cells of acute myeloblastic leukaemia (AML) are usually cultured in methylcellulose which selects for terminal dividing cells. Suspension cultures have been developed because they reflect self-renewal: the exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. We have compared the radiosensitivity of the progenitors of AML grown either in methylcellulose alone or first in suspension for 7 days before being plated in methylcellulose. Cells were harvested from leukaemic bone marrows at the moment of diagnosis. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical and immunophenotypic analysis and by the use of growth factors which do not stimulate T-lymphocytes. The cell-cycle distribution of leukaemic blasts was comparable for all the samples. This method enabled aggressive leukaemias to be selected. The radiosensitivity showed wide variations from one patient to another (Do ranging from 0.35 to 2.6 Gy) whichever culture method used. The progenitor cells capable of self-renewal were more radiosensitive (Mean Do 0.9[+-]0.4 Gy) than terminal dividing cells (Mean Do = 1.35[+-]0.5 Gy). In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. The shape of the curves was better fitted by the linear quadratic model with very low values of [alpha]/[beta], suggesting a reduced antileukaemic effect in case of fractionation.

  9. A Regulatory Network Involving β-Catenin, e-Cadherin, PI3k/Akt, and Slug Balances Self-Renewal and Differentiation of Human Pluripotent Stem Cells In Response to Wnt Signaling.

    Science.gov (United States)

    Huang, Tyng-Shyan; Li, Li; Moalim-Nour, Lilian; Jia, Deyong; Bai, Jian; Yao, Zemin; Bennett, Steffany A L; Figeys, Daniel; Wang, Lisheng

    2015-05-01

    The mechanisms underlying disparate roles of the canonical Wnt signaling pathway in maintaining self-renewal or inducing differentiation and lineage specification in embryonic stem cells (ESCs) are not clear. In this study, we provide the first demonstration that self-renewal versus differentiation of human ESCs (hESCs) in response to Wnt signaling is predominantly determined by a two-layer regulatory circuit involving β-catenin, E-cadherin, PI3K/Akt, and Slug in a time-dependent manner. Short-term upregulation of β-catenin does not lead to the activation of T-cell factor (TCF)-eGFP Wnt reporter in hESCs. Instead, it enhances E-cadherin expression on the cell membrane, thereby enhancing hESC self-renewal through E-cadherin-associated PI3K/Akt signaling. Conversely, long-term Wnt activation or loss of E-cadherin intracellular β-catenin binding domain induces TCF-eGFP activity and promotes hESC differentiation through β-catenin-induced upregulation of Slug. Enhanced expression of Slug leads to a further reduction of E-cadherin that serves as a β-catenin "sink" sequestering free cytoplasmic β-catenin. The formation of such a framework reinforces hESCs to switch from a state of temporal self-renewal associated with short-term Wnt/β-catenin activation to definitive differentiation. Stem Cells 2015;33:1419-1433. © 2015 AlphaMed Press.

  10. Structural originations of irreversible capacity loss from highly lithiated copper oxides

    International Nuclear Information System (INIS)

    Love, Corey T.; Dmowski, Wojtek; Johannes, Michelle D.; Swider-Lyons, Karen E.

    2011-01-01

    We use electrochemistry, high-energy X-ray diffraction (XRD) with pair-distribution function analysis (PDF), and density functional theory (DFT) to study the instabilities of Li 2 CuO 2 at varying state of charge. Rietveld refinement of XRD patterns revealed phase evolution from pure Li 2 CuO 2 body-centered orthorhombic (Immm) space group to multiphase compositions after cycling. The PDF showed CuO 4 square chains with varying packing during electrochemical cycling. Peaks in the G(r) at the Cu-O distance for delithiated, LiCuO 2 , showed CuO 4 square chains with reduced ionic radius for Cu in the 3+ state. At full depth of discharge to 1.5 V, CuO was observed in fractions greater than the initial impurity level which strongly affects the reversibility of the lithiation reactions contributing to capacity loss. DFT calculations showed electron removal from Cu and O during delithiation of Li 2 CuO 2 . - Graphical abstract: Structural transformation from Li 2 CuO 2 to delithiated LiCuO 2 . Highlights: → We use experimental techniques and theoretical calculation to study the instabilities of Li 2 CuO 2 . → After initial charge multiphase material persists through charge-discharge cycle. → Precipitation of CuO strongly affects electrode reversibility contributing to capacity loss. → Structural disorganization in Li 2 CuO 2 after cycling is the result of CuO 4 square chain packing. → DFT calculations show electron removal from both Cu and O during delithiation of Li 2 CuO 2 .

  11. Synthesis, characterization and dye removal ability of high capacity polymeric adsorbent: Polyaminoimide homopolymer

    Energy Technology Data Exchange (ETDEWEB)

    Mahmoodi, Niyaz Mohammad, E-mail: nm_mahmoodi@aut.ac.ir [Department of Environmental Research, Institute for Color Science and Technology, Tehran (Iran, Islamic Republic of); Najafi, Farhood [Department of Resin and Additives, Institute for Color Science and Technology, Tehran (Iran, Islamic Republic of); Khorramfar, Shooka [Department of Environmental Research, Institute for Color Science and Technology, Tehran (Iran, Islamic Republic of); Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Amini, Farrokhlegha [Department of Environmental Research, Institute for Color Science and Technology, Tehran (Iran, Islamic Republic of); Arami, Mokhtar [Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of)

    2011-12-30

    Highlights: Black-Right-Pointing-Pointer Polyaminoimide homopolymer (PAIHP) was synthesized and characterized. Black-Right-Pointing-Pointer Kinetics data followed pseudo-second order kinetic model. Black-Right-Pointing-Pointer Isotherm data followed Langmuir isotherm. Black-Right-Pointing-Pointer Q{sub 0} for DR31, DR23, DB22 and AB25 was 6667, 5555, 9090 and 5882 mg/g, respectively. Black-Right-Pointing-Pointer PAIHP was regenerated at pH 12. - Abstract: In this paper, polyaminoimide homopolymer (PAIHP) was synthesized and its dye removal ability was investigated. Physical characteristics of PAIHP were studied using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). Direct Red 31 (DR31), Direct Red 23 (DR23), Direct Black 22 (DB22) and Acid Blue 25 (AB25) were used as model compounds. The kinetic and isotherm of dye adsorption were studied. The effect of operational parameter such as adsorbent dosage, pH and salt on dye removal was evaluated. Adsorption kinetic of dyes followed pseudo-second order kinetics. The maximum dye adsorption capacity (Q{sub 0}) of PAIHP was 6667 mg/g, 5555 mg/g, 9090 mg/g and 5882 mg/g for DR31, DR23, DB22 and AB25, respectively. It was found that adsorption of DR31, DR23, DB22 and AB25 onto PAIHP followed with Langmuir isotherm. Dye desorption tests (adsorbent regeneration) showed that the maximum dye release of 90% for DR31, 86% for DR23, 87% for DB22 and 90% for AB25 were achieved in aqueous solution at pH 12. The results showed that the PAIHP as a polymeric adsorbent with high dye adsorption capacity might be a suitable alternative to remove dyes from colored wastewater.

  12. Synthesis, characterization and dye removal ability of high capacity polymeric adsorbent: Polyaminoimide homopolymer

    International Nuclear Information System (INIS)

    Mahmoodi, Niyaz Mohammad; Najafi, Farhood; Khorramfar, Shooka; Amini, Farrokhlegha; Arami, Mokhtar

    2011-01-01

    Highlights: ► Polyaminoimide homopolymer (PAIHP) was synthesized and characterized. ► Kinetics data followed pseudo-second order kinetic model. ► Isotherm data followed Langmuir isotherm. ► Q 0 for DR31, DR23, DB22 and AB25 was 6667, 5555, 9090 and 5882 mg/g, respectively. ► PAIHP was regenerated at pH 12. - Abstract: In this paper, polyaminoimide homopolymer (PAIHP) was synthesized and its dye removal ability was investigated. Physical characteristics of PAIHP were studied using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). Direct Red 31 (DR31), Direct Red 23 (DR23), Direct Black 22 (DB22) and Acid Blue 25 (AB25) were used as model compounds. The kinetic and isotherm of dye adsorption were studied. The effect of operational parameter such as adsorbent dosage, pH and salt on dye removal was evaluated. Adsorption kinetic of dyes followed pseudo-second order kinetics. The maximum dye adsorption capacity (Q 0 ) of PAIHP was 6667 mg/g, 5555 mg/g, 9090 mg/g and 5882 mg/g for DR31, DR23, DB22 and AB25, respectively. It was found that adsorption of DR31, DR23, DB22 and AB25 onto PAIHP followed with Langmuir isotherm. Dye desorption tests (adsorbent regeneration) showed that the maximum dye release of 90% for DR31, 86% for DR23, 87% for DB22 and 90% for AB25 were achieved in aqueous solution at pH 12. The results showed that the PAIHP as a polymeric adsorbent with high dye adsorption capacity might be a suitable alternative to remove dyes from colored wastewater.

  13. IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia

    Directory of Open Access Journals (Sweden)

    Yung-Che Kuo

    2018-02-01

    Full Text Available Summary: Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs. However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R, and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis. : In this article, Huang and colleagues demonstrate that niche hypoxia promotes symmetric self-renewal proliferation and migration of PGC-like CD49f+AP+GSCs through IGF-IR regulation. Using a serum-free culture system, the crosstalk between IGF-1R and CXCR4 signaling was discovered. This work demonstrated that embryonic hypoxia synergistically cooperated with IGF-1R signaling to regulate the symmetric self-renewal and migration of PGC-like GSCs through a HIF-2α–OCT4/CXCR4 loop. Keywords: hypoxia, niche, germline stem cells, self-renewal, migration, IGF-1R, HIF-2α, OCT4, SDF-1, CXCR4

  14. Random oriented hexagonal nickel hydroxide nanoplates grown on graphene as binder free anode for lithium ion battery with high capacity

    Science.gov (United States)

    Du, Yingjie; Ma, Hu; Guo, Mingxuan; Gao, Tie; Li, Haibo

    2018-05-01

    In this work, two-step method has been employed to prepare random oriented hexagonal hydroxide nanoplates on graphene (Ni(OH)2@G) as binder free anode for lithium ion battery (LIB) with high capacity. The morphology, microstructure, crystal phase and elemental bonding have been characterized. When evaluated as anode for LIB, the Ni(OH)2@G exhibited high initial discharge capacity of 1318 mAh/g at the current density of 50 mA/g. After 80 cycles, the capacity was maintained at 834 mAh/g, implying 63.3% remaining. Even the charge rate was increased to 2000 mA/g, an impressive capacity of 141 mAh/g can be obtained, indicating good rate capability. The superior LIB behavior of Ni(OH)2@G is ascribed to the excellent combination between Ni(OH)2 nanoplates and graphene via both covalent chemical bonding and van der Waals interactions.

  15. The effects of high intensity interval training in normobaric hypoxia on aerobic capacity in basketball players.

    Science.gov (United States)

    Czuba, Miłosz; Zając, Adam; Maszczyk, Adam; Roczniok, Robert; Poprzęcki, Stanisław; Garbaciak, Wiesław; Zając, Tomasz

    2013-12-18

    The aim of the present study was to evaluate the efficacy of 3-week high intensity interval training in normobaric hypoxia (IHT) on aerobic capacity in basketball players. Twelve male well trained basketball players, randomly divided into a hypoxia (H) group (n=6; age: 22±1.6 years; VO2max: 52.6±3.9 ml/kg/min; body height - BH: 188.8±6.1 cm; body mass - BM: 83.9±7.2 kg; % of body fat - FAT%: 11.2±3.1%), and a control (C) group (n=6; age: 22±2.4 years; VO2max: 53.0±5.2 ml/kg/min; BH: 194.3 ± 6.6 cm; BM: 99.9±11.1 kg; FAT% 11.0±2.8 %) took part in the study. The training program applied during the study was the same for both groups, but with different environmental conditions during the selected interval training sessions. For 3 weeks, all subjects performed three high intensity interval training sessions per week. During the interval training sessions, the H group trained in a normobaric hypoxic chamber at a simulated altitude of 2500 m, while the group C performed interval training sessions under normoxia conditions also inside the chamber. Each interval running training sessions consisted of four to five 4 min bouts at 90% of VO2max velocity determined in hypoxia (vVO2max-hyp) for the H group and 90% of velocity at VO2max determined in normoxia for the group C. The statistical post-hoc analysis showed that the training in hypoxia caused a significant (ptraining in normoxia caused an increase (ptraining protocol with high intensity intervals (4 to 5 × 4 min bouts at 90% of vVO2max-hyp) is an effective training means for improving aerobic capacity at sea level in basketball players.

  16. Polyethylenimine-modified fungal biomass as a high-capacity biosorbent for Cr(VI) anions: sorption capacity and uptake mechanisms.

    Science.gov (United States)

    Deng, Shubo; Ting, Yen Peng

    2005-11-01

    Heavy metal pollution in the aqueous environment is a problem of global concern. Biosorption has been considered as a promising technology for the removal of low levels of toxic metals from industrial effluents and natural waters. A modified fungal biomass of Penicillium chrysogenum with positive surface charges was prepared by grafting polyethylenimine (PEI) onto the biomass surface in a two-step reaction. The presence of PEI on the biomass surface was verified by FTIR and X-ray photoelectron spectroscopy (XPS) analyses. Due to the high density of amine groups in the long chains of PEI molecules on the surface, the modified biomass was found to possess positive zeta potential at pH below 10.4 as well as high sorption capacity for anionic Cr(VI). Using the Langmuir adsorption isotherm, the maximum sorption capacity for Cr(VI) at a pH range of 4.3-5.5 was 5.37 mmol/g of biomass dry weight, the highest sorption capacity for Cr(VI) compared to other sorbents reported in the literature. Scanning electronic microscopy (SEM) provided evidence of chromium aggregates formed on the biomass surface. XPS results verified the presence of Cr(III) on the biomass surface in the pH range 2.5-10.5, suggesting that some Cr(VI) anions were reduced to Cr(III) during the sorption. The sorption kinetics indicated that redox reaction occurred on the biomass surface, and whether the converted Cr(III) ions were released to solution or adsorbed on the biomass depended on the solution pH. Sorption mechanisms including electrostatic interaction, chelation, and precipitation were found to be involved in the complex sorption of chromium on the PEI-modified biomass.

  17. High efficiency-large capacity circulating water pump for Hamaoka Nuclear Power Station unit No.3

    International Nuclear Information System (INIS)

    Ito, Akihiko; Sasamuro, Takemi; Takeda, Hirohisa.

    1988-01-01

    No.3 plant in the Hamaoka Nuclear Power Station, Chube Electric Power Co., Inc. is the latest plant of 1100 MW class BWR type, which began the commercial operation in August, 1987. The seawater intake and discharge system of this plant is composed of the channel exceeding 2 km in the total length from the intake tower to the discharge port. The circulating water pump installed in this system has the capacity of 1620 m 3 /min and the total head of 16.5 m, which are the largest in the world. It attained the efficiency as high as more than 90%. Three pumps supply seawater to three-body condensers. The design of the impeller and the casing for obtaining high efficiency, the structural design for facilitating maintenance, the manufacture of a model pump and the performance test using it and so on are reported. The most important item in the manufacture was the form of the onebody impeller weighing 4.5t. The confirmation of the performance of the actual machines was carried out as a part of the synthetic function confirmation test at the power station, and the flow rate was measured with Pitot tubes and ultrasonic flowmeters. (Kako, I.)

  18. Nanostructured Block Polymer Membranes as High Capacity Adsorbers for the Capture of Metal Ions from Water

    Science.gov (United States)

    Boudouris, Bryan; Weidman, Jacob; Mulvenna, Ryan; Phillip, William

    The efficient removal of metal ions from aqueous streams is of significant import in applications ranging from industrial waste treatment to the purification of drinking water. An emerging paradigm associated with this separation is one that utilizes membrane adsorbers as a means by which to bind metal salt contaminants. Here, we demonstrate that the casting of an A-B-C triblock polymer using the self-assembly and non-solvent induced phase separation (SNIPS) methodology results in a nanoporous membrane geometry. The nature of the triblock polymer affords an extremely high density of binding sites within the membrane. As such, we demonstrate that the membranes with binding capacities equal to that of state-of-the-art packed bed columns. Moreover, because the affinity of the C moiety can be tuned, highly selective binding events can occur based solely on the chemistry of the block polymer and the metal ions in solution (i.e., in a manner that is independent of the size of the metal ions). Due to these combined facts, these membranes efficiently remove heavy metal (e.g., lead- and cadmium-based) salts from contaminated water streams with greater than 95% efficiency. Finally, we show that the membranes can be regenerated through a simple treatment in order to provide long-lasting adsorber systems as well. Thus, it is anticipated that these nanostructured triblock polymer membranes are a platform by which to obtain next-generation water purification processes.

  19. State Violence and Oppositional Protest in High-Capacity Authoritarian Regimes

    Directory of Open Access Journals (Sweden)

    Hank Johnston

    2012-05-01

    Full Text Available This examination of the mobilization-repression nexus in high-capacity authoritarian regimes draws on examples from China, Russia, Iran, and several Middle Eastern states to develop a framework for analyzing state violence and how political oppositions are organized. The study examines middle and low levels of state violence, the provincial and municipal organization of party and regime, and the police, private militias, and thugs as low-level enforcers, and focuses on: (1 the complexity of the state’s apparatus of repression and control and how different levels exercise different forms of violence against activists; (2 the creativity of the opposition’s actions to voice its demands and avoid repression and surveillance; and (3 the recursive relationship between the two, a dark dance between state and opposition with high stakes for both. Hierarchical analysis at national, provincial, and local levels, and lateral analysis across these levels, where elite interests frequently diverge, show that intersections and gaps on both axes can create lapses in social control and openings the opposition. These free spaces of speech and innovative action give rise to novel ways to keep oppositional sentiments in the public forum. The article offers several propositions for analyzing repression and state violence at various levels, and, similarly, the various ways that these free spaces occur.

  20. Study on a high capacity two-stage free piston Stirling cryocooler working around 30 K

    Science.gov (United States)

    Wang, Xiaotao; Zhu, Jian; Chen, Shuai; Dai, Wei; Li, Ke; Pang, Xiaomin; Yu, Guoyao; Luo, Ercang

    2016-12-01

    This paper presents a two-stage high-capacity free-piston Stirling cryocooler driven by a linear compressor to meet the requirement of the high temperature superconductor (HTS) motor applications. The cryocooler system comprises a single piston linear compressor, a two-stage free piston Stirling cryocooler and a passive oscillator. A single stepped displacer configuration was adopted. A numerical model based on the thermoacoustic theory was used to optimize the system operating and structure parameters. Distributions of pressure wave, phase differences between the pressure wave and the volume flow rate and different energy flows are presented for a better understanding of the system. Some characterizing experimental results are presented. Thus far, the cryocooler has reached a lowest cold-head temperature of 27.6 K and achieved a cooling power of 78 W at 40 K with an input electric power of 3.2 kW, which indicates a relative Carnot efficiency of 14.8%. When the cold-head temperature increased to 77 K, the cooling power reached 284 W with a relative Carnot efficiency of 25.9%. The influences of different parameters such as mean pressure, input electric power and cold-head temperature are also investigated.

  1. The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity.

    Science.gov (United States)

    Rauckhorst, Adam J; Gray, Lawrence R; Sheldon, Ryan D; Fu, Xiaorong; Pewa, Alvin D; Feddersen, Charlotte R; Dupuy, Adam J; Gibson-Corley, Katherine N; Cox, James E; Burgess, Shawn C; Taylor, Eric B

    2017-11-01

    Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions. We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13 C-lactate/ 13 C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity. Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation. By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  2. High-capacity transport, floor area ratio and its relationship with urbanization of metropolitan areas

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho da Costa, B.L. de; Carvalho da Costa, F.B. de

    2016-07-01

    Most of the world’s population lives in urban areas (54%). Near 42% of the global urban population live in cities with more than 1 million inhabitants, where problems associated with urban sprawl such as informal settlement, social-economic changes, environmental degradation and deficient high-capacity transport (HCT) systems are common. Meanwhile, urbanization and its associated transportation infrastructure define the relationship between city and countryside, between the city’s inner core and the periphery, between the citizen and his right to move. This article discusses and presents an overview about the relationship between the planning and extension of HCT systems and urban planning, (in the figure of the floor-area ratio - FAR- prescribed in regulations). The methodological approach consists of drawing a conceptual framework and studying 33 different cities of metropolitan areas on five continents. It’s noticed that areas in cities with a high construction potential but with an insufficient HCT negatively influence in urban mobility and hence the right to the city. We consider right to the city the various social and fundamental rights that, among others, includes the right to public transportation. Therefore there’s a real need of an integrated approach of community participation, FAR distribution, urban planning and transportation planning and so that urbanization, inevitable these days, takes place in a fair and harmonious way. (Author)