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Sample records for high-density growth arrest

  1. High-density growth arrest in Ras-transformed cells: low Cdk kinase activities in spite of absence of p27(Kip) Cdk-complexes.

    Science.gov (United States)

    Groth, Anja; Willumsen, Berthe M

    2005-09-01

    The ras oncogene transforms immortalized, contact-inhibited non-malignant murine fibroblasts into cells that are focus forming, exhibit increased saturation density, and are malignant in suitable hosts. Here, we examined changes in cell cycle control complexes as normal and Ras-transformed cells ceased to grow exponentially, to reveal the molecular basis for Ras-dependent focus formation. As normal cells entered density-dependent arrest, cyclin D1 decreased while cyclin D2 was induced and replaced D1 in Cdk4 complexes. Concomitantly, p27(Kip1) levels rose and the inhibitor accumulated in both Cdk4 and Cdk2 complexes, as these kinases were inactivated. Ras-transformed cells failed to arrest at normal saturation density and showed no significant alterations in cell control complexes at this point. Yet, at an elevated density the Ras-transformed cells ceased to proliferate and entered a quiescent-like state with low Cdk4 and Cdk2 activity. Surprisingly, this delayed arrest was molecularly distinct from contact inhibition of normal cells, as it occurred in the absence of p27(Kip1) induction and cyclin D1 levels remained high. This demonstrates that although oncogenic Ras efficiently disabled the normal response to contact inhibition, a separate back-up mechanism enforced cell cycle arrest at higher cell density.

  2. Acquired Upper Extremity Growth Arrest.

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    Gauger, Erich M; Casnovsky, Lauren L; Gauger, Erica J; Bohn, Deborah C; Van Heest, Ann E

    2017-01-01

    This study reviewed the clinical history and management of acquired growth arrest in the upper extremity in pediatric patients. The records of all patients presenting from 1996 to 2012 with radiographically proven acquired growth arrest were reviewed. Records were examined to determine the etiology and site of growth arrest, management, and complications. Patients with tumors or hereditary etiology were excluded. A total of 44 patients (24 boys and 20 girls) with 51 physeal arrests who presented at a mean age of 10.6 years (range, 0.8-18.2 years) were included in the study. The distal radius was the most common site (n=24), followed by the distal humerus (n=8), metacarpal (n=6), distal ulna (n=5), proximal humerus (n=4), radial head (n=3), and olecranon (n=1). Growth arrest was secondary to trauma (n=22), infection (n=11), idiopathy (n=6), inflammation (n=2), compartment syndrome (n=2), and avascular necrosis (n=1). Twenty-six patients (59%) underwent surgical intervention to address deformity caused by the physeal arrest. Operative procedures included ipsilateral unaffected bone epiphysiodesis (n=21), shortening osteotomy (n=10), lengthening osteotomy (n=8), excision of physeal bar or bone fragment (n=2), angular correction osteotomy (n=1), and creation of single bone forearm (n=1). Four complications occurred; 3 of these required additional procedures. Acquired upper extremity growth arrest usually is caused by trauma or infection, and the most frequent site is the distal radius. Growth disturbances due to premature arrest can be treated effectively with epiphysiodesis or osteotomy. In this series, the specific site of anatomic growth arrest was the primary factor in determining treatment. [Orthopedics. 2017; 40(1):e95-e103.]. Copyright 2016, SLACK Incorporated.

  3. Escaping growth arrest in cancer

    NARCIS (Netherlands)

    Kortlever, R.M.

    2008-01-01

    We now have a general idea of which genes and cellular pathways are central in cancer development: uncontrolled growth governs establishment and spread of the disease. Nevertheless, to fully appreciate the consequences of the interplay of driver mutations in this genetic disease it is imperative we

  4. Growth of high-density horizontally aligned SWNT arrays using Trojan catalysts.

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    Hu, Yue; Kang, Lixing; Zhao, Qiuchen; Zhong, Hua; Zhang, Shuchen; Yang, Liangwei; Wang, Zequn; Lin, Jingjing; Li, Qingwen; Zhang, Zhiyong; Peng, Lianmao; Liu, Zhongfan; Zhang, Jin

    2015-01-20

    Single-walled carbon nanotube (SWNT)-based electronics have been regarded as one of the most promising candidate technologies to replace or supplement silicon-based electronics in the future. These applications require high-density horizontally aligned SWNT arrays. During the past decade, significant efforts have been directed towards growth of high-density SWNT arrays. However, obtaining SWNT arrays with suitable density and quality still remains a big challenge. Herein, we develop a rational approach to grow SWNT arrays with ultra-high density using Trojan catalysts. The density can be as high as 130 SWNTs μm(-1). Field-effect transistors fabricated with our SWNT arrays exhibit a record drive current density of -467.09 μA μm(-1) and an on-conductance of 233.55 μS μm(-1). Radio frequency transistors fabricated on these samples exhibit high intrinsic fT and fMAX of 6.94 and 14.01 GHz, respectively. These results confirm our high-density SWNT arrays are strong candidates for applications in electronics.

  5. Growth of High-Density Zinc Oxide Nanorods on Porous Silicon by Thermal Evaporation

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    Nurul Izni Rusli

    2012-12-01

    Full Text Available The formation of high-density zinc oxide (ZnO nanorods on porous silicon (PS substrates at growth temperatures of 600–1000 °C by a simple thermal evaporation of zinc (Zn powder in the presence of oxygen (O2 gas was systematically investigated. The high-density growth of ZnO nanorods with (0002 orientation over a large area was attributed to the rough surface of PS, which provides appropriate planes to promote deposition of Zn or ZnOx seeds as nucleation sites for the subsequent growth of ZnO nanorods. The geometrical morphologies of ZnO nanorods are determined by the ZnOx seed structures, i.e., cluster or layer structures. The flower-like hexagonal-faceted ZnO nanorods grown at 600 °C seem to be generated from the sparsely distributed ZnOx nanoclusters. Vertically aligned hexagonal-faceted ZnO nanorods grown at 800 °C may be inferred from the formation of dense arrays of ZnOx clusters. The formation of disordered ZnO nanorods formed at 1000 °C may due to the formation of a ZnOx seed layer. The growth mechanism involved has been described by a combination of self-catalyzed vapor-liquid-solid (VLS and vapor-solid (VS mechanism. The results suggest that for a more precise study on the growth of ZnO nanostructures involving the introduction of seeds, the initial seed structures must be taken into account given their significant effects.

  6. High-density polymer microarrays: identifying synthetic polymers that control human embryonic stem cell growth.

    Science.gov (United States)

    Hansen, Anne; Mjoseng, Heidi K; Zhang, Rong; Kalloudis, Michail; Koutsos, Vasileios; de Sousa, Paul A; Bradley, Mark

    2014-06-01

    The fabrication of high-density polymer microarray is described, allowing the simultaneous and efficient evaluation of more than 7000 different polymers in a single-cellular-based screen. These high-density polymer arrays are applied in the search for synthetic substrates for hESCs culture. Up-scaling of the identified hit polymers enables long-term cellular cultivation and promoted successful stem-cell maintenance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Development of a Novel High-Density [3H]Hypoxanthine Scintillation Proximity Assay To Assess Plasmodium falciparum Growth.

    Science.gov (United States)

    de Cózar, Cristina; Caballero, Iván; Colmenarejo, Gonzalo; Sanz, Laura M; Álvarez-Ruiz, Emilio; Gamo, Francisco-Javier; Cid, Concepción

    2016-10-01

    The discovery and development of new antimalarial drugs are becoming imperative because of the spread of resistance to current clinical treatments. The lack of robustly validated antimalarial targets and the difficulties with the building in of whole-cell activity in screening hits are hampering target-based approaches. However, phenotypic screens of structurally diverse molecule libraries are offering new opportunities for the identification of novel antimalarials. Several methodologies can be used to determine the whole-cell in vitro potencies of antimalarial hits. The [(3)H]hypoxanthine incorporation assay is considered the "gold standard" assay for measurement of the activity of antimalarial compounds against intraerythrocytic forms of Plasmodium falciparum However, the method has important limitations, as the assay is not amenable for high-throughput screening since it remains associated with the 96-well plate format. We have overcome this drawback by adapting the [(3)H]hypoxanthine incorporation method to a 384-well high-density format by coupling a homogeneous scintillation proximity assay (SPA) and thus eliminating the limiting filtration step. This SPA has been validated using a diverse set of 1,000 molecules, including both a representative set from the Tres Cantos Antimalarial Set (TCAMS) of compounds and molecules inactive against whole cells. The results were compared with those from the P. falciparum lactate dehydrogenase whole-cell assay, another method that is well established as a surrogate for parasite growth and is amenable for high-throughput screening. The results obtained demonstrate that the SPA-based [(3)H]hypoxanthine incorporation assay is a suitable design that is adaptable to high-throughput antimalarial drug screening and that maintains the features, robustness, and reliability of the standard filtration hypoxanthine incorporation method.

  8. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

    Science.gov (United States)

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun

    2015-10-01

    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

  9. Coxa vara with proximal femoral growth arrest in patients who had neonatal extracorporeal membrane oxygenation.

    Science.gov (United States)

    DiFazio, Rachel L; Kocher, Minider S; Berven, Sigurd; Kasser, James

    2003-01-01

    This is a retrospective review of four patients in whom a pattern of coxa vara with proximal femoral growth arrest and metaphyseal irregularities developed. These patients were all treated with neonatal extracorporeal membrane oxygenation and presented with a progressive gait disturbance and pain, leg-length discrepancy, and limited abduction. Imaging revealed coxa vara with proximal femoral growth arrest. Two patients (three hips) underwent proximal femoral valgus osteotomy, one patient underwent fixation of a femoral neck fracture with subsequent greater trochanter transfer, and one patient is being observed. This case series suggests an association between neonatal extracorporeal membrane oxygenation and this unusual pattern of coxa vara with proximal femoral growth arrest.

  10. Improved growth performance in rainbow trout Oncorhynchus mykiss reared at high densities is linked to increased energy retention

    DEFF Research Database (Denmark)

    Laursen, Danielle Caroline; Larsen, Bodil Katrine; Skov, Peter Vilhelm

    2015-01-01

    ), a higher fraction of the dietary energy intake was used to fuel activity rather than growth, as evidenced by significantly higher routine metabolism, reduced feed utilisation efficiency and a tendency for lower growth performance compared to fish reared at the higher densities. These results indicate......Behaviour has been suggested as an underlying factor influencing how rearing density affects growth performance in Salmonid fishes. At low densities there is an elevated intensity of aggressive interactions and the formation of dominance hierarchies. As density increases, it is commonly assumed...... that aggression decreases, as the cost and effort required to establish and maintain dominance hierarchies increase. The increased energy expenditure associated with aggressive interactions has been identified as one mechanism causing a reduced efficiency in feed utilisation and therefore decreased growth...

  11. Growth Arrest on Inhibition of Nonsense-Mediated Decay Is Mediated by Noncoding RNA GAS5

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    Mirna Mourtada-Maarabouni

    2013-01-01

    Full Text Available Nonsense-mediated decay is a key RNA surveillance mechanism responsible for the rapid degradation of mRNAs containing premature termination codons and hence prevents the synthesis of truncated proteins. More recently, it has been shown that nonsense-mediated decay also has broader significance in controlling the expression of a significant proportion of the transcriptome. The importance of this mechanism to the mammalian cell is demonstrated by the observation that its inhibition causes growth arrest. The noncoding RNA growth arrest specific transcript 5 (GAS5 has recently been shown to play a key role in growth arrest induced by several mechanisms, including serum withdrawal and treatment with the mTOR inhibitor rapamycin. Here we show that inhibition of nonsense-mediated decay in several human lymphocyte cell lines causes growth arrest, and siRNA-mediated downregulation of GAS5 in these cells significantly alleviates the inhibitory effects observed. These observations hold true for inhibition of nonsense-mediated decay both through RNA interference and through pharmacological inhibition by aminoglycoside antibiotics gentamycin and G418. These studies have important implications for ototoxicity and nephrotoxicity caused by gentamycin and for the proposed use of NMD inhibition in treating genetic disease. This report further demonstrates the critical role played by GAS5 in the growth arrest of mammalian cells.

  12. Selective area growth of high-density GaN nanowire arrays on Si(111) using thin AlN seeding layers

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    Wu, C. H.; Lee, P. Y.; Chen, K. Y.; Tseng, Y. T.; Wang, Y. L.; Cheng, K. Y.

    2016-11-01

    Selective area growth (SAG) of high-density (2.5×109 cm-2) GaN nanowires (NWs) on Si(111) substrate by plasma-assisted molecular beam epitaxy is presented. The effects of morphology and thickness of the AlN seeding layer on the quality of SAG GaN NWs are investigated. A thin AlN seeding layer of 30 nm thick with a surface roughness of less than 0.5 nm is suitable for high quality SAG GaN NWs growth. High-density AlN nanopedestal arrays used as seeds for SAG GaN NWs are fabricated from thin AlN seeding layers using soft nanoimprint lithography. By adjusting the growth temperature and Ga/N flux ratio, hexagonal shaped SAG GaN NWs are realized. The quality of SAG GaN NWs is evaluated by low temperature photoluminescence (PL) measurements. Three major groups of PL peaks at 3.47, 3.45, and 3.41 eV are identified. The peak at 3.471 eV is related to the neutral donor-bound exciton emission, and the 3.41 eV broadband emission is attributed to stacking faults or structural defects. The 3.45 eV peak is identified as the emission due to exciton recombination at polar inversion domain boundaries of NWs.

  13. ExbB Cytoplasmic Loop Deletions Cause Immediate, Proton Motive Force-Independent Growth Arrest

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    Bulathsinghala, Charles M.; Jana, Bimal; Baker, Kristin R.

    2013-01-01

    The Escherichia coli TonB system consists of the cytoplasmic membrane proteins TonB, ExbB, and ExbD and multiple outer membrane active transporters for diverse iron siderophores and vitamin B12. The cytoplasmic membrane proteins harvest and transmit the proton motive force (PMF) to outer membrane transporters. This system, which spans the cell envelope, has only one component with a significant cytoplasmic presence, ExbB. Characterization of sequential 10-residue deletions in the ExbB cytoplasmic loop (residues 40 to 129; referred to as Δ10 proteins) revealed that it was required for all TonB-dependent activities, including interaction between the periplasmic domains of TonB and ExbD. Expression of eight out of nine of the Δ10 proteins at chromosomal levels led to immediate, but reversible, growth arrest. Arrest was not due to collapse of the PMF and did not require the presence of ExbD or TonB. All Δ10 proteins that caused growth arrest were dominant for that phenotype. However, several were not dominant for iron transport, indicating that growth arrest was an intrinsic property of the Δ10 variants, whether or not they could associate with wild-type ExbB proteins. The lack of dominance in iron transport also ruled out trivial explanations for growth arrest, such as high-level induction. Taken together, the data suggest that growth arrest reflected a changed interaction between the ExbB cytoplasmic loop and one or more unknown growth-regulatory proteins. Consistent with that, a large proportion of the ExbB cytoplasmic loop between transmembrane domain 1 (TMD1) and TMD2 is predicted to be disordered, suggesting the need for interaction with one or more cytoplasmic proteins to induce a final structure. PMID:23913327

  14. Growth of high-density ZnO nanorods on wood with enhanced photostability, flame retardancy and water repellency

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    Kong, Lizhuo; Tu, Kunkun; Guan, Hao; Wang, Xiaoqing

    2017-06-01

    Zinc oxide (ZnO) nanorod arrays were successfully assembled on the wood surface in situ via a two-step process consisting of formation of ZnO seeds and subsequent crystal growth under hydrothermal conditions at a low temperature. The morphology and crystalline structure of the formed ZnO nanorods were studied by field-emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD). Highly dense and uniform arrays of ZnO nanorods with well-defined hexagonal facets were generated on the wood surface by tuning the concentration of the ZnO growth solution during the hydrothermal treatment. Accelerated weathering tests indicated that the assembled ZnO nanorod arrays were highly protective against UV radiation and greatly enhanced the photostability of the coated wood. Meanwhile, the ZnO nanorod-coated wood can withstand continuous exposure to flame with only minor smoldering in contrast with the pristine wood catching fire easily and burning rapidly. Moreover, when further modified with low-surface-energy stearic acid, the ZnO nanorod decorated wood surface can be transformed into a superhydrophobic surface, with a water contact angle (CA) of ∼154°. Such ZnO nanorod-modified woods with enhanced photostability, flame retardancy and water repellency offer an interesting alternative to conventional wood preservation strategies, highlighting their potential applications in some novel wood products.

  15. EFFECTS OF DWARFING GISELA 5 ROOTSTOCK ON REPRODUCTIVE POTENTIAL, VEGETATIVE GROWTH, AND PHYSIOLOGICAL FEATURES OF SOME SWEET CHERRY CULTIVARS IN HIGH-DENSITY SWEET CHERRY ORCHARDS

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    Monica Popescu

    2015-12-01

    Full Text Available Gisela 5 rootstock is most important in terms of reducing the vigor of growth. The varieties grafted on Gisela 5 had good horticultural results in terms of yield, adaptability and dwarf growth. This study was aimed to evaluate the growth and physiological behavior of the most popular sweet cherry cultivars in Europe grafted of Gisela 5 rootstock in one of the most important fruit growing area from Romania. The rootstock – scion combinations namely Skeena, Kordia and Ferrovia were grafted on Gisela 5 dwarf rootstocks. Gisela 5 influenced significantly the trunk cross section area among all the tested cultivars (p<0.05. Ferrovia cultivar was the most vigorous in terms of trunk cross sectional area and total annual growth length. Total annual growth was lower for Kordia (1225.61 cm. The ratio between Chl a and Chl b seems to be constant in all grafted plants. The photosynthesis rate [µ mol (CO2 m-2 s-1] varied from 24.12 µ mol (CO2 m-2 s-1 in the Kordia grafted sweet cherry variety to 25.80 µ mol (CO2 m-2 s-1 in the Ferrovia sweet cherry cultivar. Data obtained from field measurements and laboratory observations demonstrated that the Gisela 5 rootstock is compatible with foreign sweet cherry varieties under the selected growing area and can be used to achieve high-density sweet cherry orchards.

  16. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

    DEFF Research Database (Denmark)

    Suzuki, Harukazu; Forrest, Alistair R R; van Nimwegen, Erik

    2009-01-01

    Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites...

  17. Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Martin, Katherine J.; Kenny, Paraic A.; Xhaja, Kris; Bosch, Irene; Yaswen, Paul; Bissell, Mina J.

    2006-02-08

    To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines. We show that genes that are significantly lower in the organized, growth arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.

  18. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

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    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  19. Physeal growth arrest after tibial lengthening in achondroplasia

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    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who und...

  20. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    Science.gov (United States)

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

  1. Physeal growth arrest after tibial lengthening in achondroplasia

    Science.gov (United States)

    2012-01-01

    Background and purpose Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with acondroplasia. Methods We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Results Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Interpretation Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence—especially when lengthening of more than 50% is attempted. PMID:22489887

  2. High Density Matter

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    Stone J.R.

    2013-12-01

    Full Text Available The microscopic composition and properties of matter at super-saturation densities have been the subject of intense investigation for decades. The scarcity of experimental and observational data has led to the necessary reliance on theoretical models. There remains great uncertainty in these models which, of necessity, have to go beyond the over-simple assumption that high density matter consists only of nucleons and leptons. Heavy strange baryons, mesons and quark matter in different forms and phases have to be included to fulfil basic requirements of fundamental laws of physics. In this contribution latest developments in construction of the Equation of State (EoS of high-density matter at zero and finite temperature assuming different composition of matter will be discussed. Critical comparison of model EoS with available experimental data from heavy ion collisions and observations on neutron stars, including gravitational mass, radii and cooling patterns and data on X-ray burst sources and low mass X-ray binaries are made. Fundamental differences between the EoS of low-density, high temperature matter, such as is created in heavy ion collisions and of high-density, low temperature compact objects is discussed.

  3. Growth-arrest-specific protein 2 inhibits cell division in Xenopus embryos.

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    Tong Zhang

    Full Text Available BACKGROUND: Growth-arrest-specific 2 gene was originally identified in murine fibroblasts under growth arrest conditions. Furthermore, serum stimulation of quiescent, non-dividing cells leads to the down-regulation of gas2 and results in re-entry into the cell cycle. Cytoskeleton rearrangements are critical for cell cycle progression and cell division and the Gas2 protein has been shown to co-localize with actin and microtubules in interphase mammalian cells. Despite these findings, direct evidence supporting a role for Gas2 in the mechanism of cell division has not been reported. METHODOLOGY AND PRINCIPAL FINDINGS: To determine whether the Gas2 protein plays a role in cell division, we over-expressed the full-length Gas2 protein and Gas2 truncations containing either the actin-binding CH domain or the tubulin-binding Gas2 domain in Xenopus laevis embryos. We found that both the full-length Gas2 protein and the Gas2 domain, but not the CH domain, inhibited cell division and resulted in multinucleated cells. The observation that Gas2 domain alone can arrest cell division suggests that Gas2 function is mediated by microtubule binding. Gas2 co-localized with microtubules at the cell cortex of Gas2-injected Xenopus embryos using cryo-confocal microscopy and co-sedimented with microtubules in cytoskeleton co-sedimentation assays. To investigate the mechanism of Gas2-induced cell division arrest, we showed, using a wound-induced contractile array assay, that Gas2 stabilized microtubules. Finally, electron microscopy studies demonstrated that Gas2 bundled microtubules into higher-order structures. CONCLUSION AND SIGNIFICANCE: Our experiments show that Gas2 inhibits cell division in Xenopus embryos. We propose that Gas2 function is mediated by binding and bundling microtubules, leading to cell division arrest.

  4. p53 oligomerization status modulates cell fate decisions between growth, arrest and apoptosis.

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    Fischer, Nicholas W; Prodeus, Aaron; Malkin, David; Gariépy, Jean

    2016-12-01

    Mutations in the oligomerization domain of p53 are genetically linked to cancer susceptibility in Li-Fraumeni Syndrome. These mutations typically alter the oligomeric state of p53 and impair its transcriptional activity. Activation of p53 through tetramerization is required for its tumor suppressive function by inducing transcriptional programs that lead to cell fate decisions such as cell cycle arrest or apoptosis. How p53 chooses between these cell fate outcomes remains unclear. Here, we use 5 oligomeric variants of p53, including 2 novel p53 constructs, that yield either monomeric, dimeric or tetrameric forms of p53 and demonstrate that they induce distinct cellular activities and gene expression profiles that lead to different cell fate outcomes. We report that dimeric p53 variants are cytostatic and can arrest cell growth, but lack the ability to trigger apoptosis in p53-null cells. In contrast, p53 tetramers induce rapid apoptosis and cell growth arrest, while a monomeric variant is functionally inactive, supporting cell growth. In particular, the expression of pro-arrest CDKN1A and pro-apoptotic P53AIP1 genes are important cell fate determinants that are differentially regulated by the oligomeric state of p53. This study suggests that the most abundant oligomeric species of p53 present in resting cells, namely p53 dimers, neither promote cell growth or cell death and that shifting the oligomeric state equilibrium of p53 in cells toward monomers or tetramers is a key parameter in p53-based cell fate decisions.

  5. Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review

    Directory of Open Access Journals (Sweden)

    Shoji Kaku

    2015-01-01

    Full Text Available Progressive fetal growth restriction (FGR is often an indication for delivery. In dichorionic diamniotic (DD twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR, the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for ≥2 weeks before 30 weeks of gestation. The interval from growth arrest to delivery was 21–24 days and the discordance was 33.7–49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus.

  6. Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth.

    Science.gov (United States)

    Akkus, O; Rimnac, C M

    2001-06-01

    Knowledge of kinetics of fatigue crack growth of microcracks is important so as to understand the dynamics of bone adaptation, remodeling, and the etiology of fatigue-based failures of cortical bone tissue. In this respect, theoretical models (Taylor, J. Biomech., 31 (1998) 587-592; Taylor and Prendergast, Proc. Instn. Mech. Engrs. Part H 211 (1997) 369-375) of microcrack growth in cortical bone have predicted a decreasing microcrack growth rate with increasing microcrack length. However, these predictions have not been observed directly. This study investigated microcrack growth and arrest through observations of surface microcracks during cyclic loading (R=0.1, 50-80MPa) of human femoral cortical bone (male, n=4, age range: 37-40yr) utilizing a video microscopy system. The change in crack length and orientation of eight surface microcracks were measured with the number of fatigue cycles from four specimens. At the applied cyclic stresses, the microcracks propagated and arrested in generally less than 10,000 cycles. The fatigue crack growth rate of all microcracks decreased with increasing crack length following initial identification, consistent with theoretical predictions. The growth rate of the microcracks was observed to be in the range of 5x10(-5) to 5x10(-7)mmcycle(-1). In addition, many of the microcracks were observed not to grow beyond 150 microm and a cyclic stress intensity factor of 0.5MNm(-3/2). The results of this study suggest that cortical bone tissue may resist fracture at the microscale by deceleration of fatigue crack growth and arrest of microcracks.

  7. Direct Growth of Carbon Nanotubes on New High-Density 3D Pyramid-Shaped Microelectrode Arrays for Brain-Machine Interfaces

    Directory of Open Access Journals (Sweden)

    Bahareh Ghane Motlagh

    2016-09-01

    Full Text Available Silicon micromachined, high-density, pyramid-shaped neural microelectrode arrays (MEAs have been designed and fabricated for intracortical 3D recording and stimulation. The novel architecture of this MEA has made it unique among the currently available micromachined electrode arrays, as it has provided higher density contacts between the electrodes and targeted neural tissue facilitating recording from different depths of the brain. Our novel masking technique enhances uniform tip-exposure for variable-height electrodes and improves process time and cost significantly. The tips of the electrodes have been coated with platinum (Pt. We have reported for the first time a selective direct growth of carbon nanotubes (CNTs on the tips of 3D MEAs using the Pt coating as a catalyzer. The average impedance of the CNT-coated electrodes at 1 kHz is 14 kΩ. The CNT coating led to a 5-fold decrease of the impedance and a 600-fold increase in charge transfer compared with the Pt electrode.

  8. MR imaging of pituitary hyperplasia in a child with growth arrest and primary hypothyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Papakonstantinou, O.; Bakantaki, A.; Papadaki, E.; Gourtsoyiannis, N. [Dept. of Radiology, Medical School, University of Crete, Heraklion (Greece); Bitsori, M.; Mamoulakis, D. [Dept. of Pediatrics, Medical School, University of Crete, Heraklion (Greece)

    2000-03-01

    Magnetic resonance imaging of pituitary hyperplasia has been rarely described in children with primary hypothyroidism. We report a case of pituitary hyperplasia in a child presented with significant growth arrest and laboratory evidence of hypothyroidism. Magnetic resonance imaging revealed symmetrical pituitary enlargement simulating macroadenoma. After thyroid hormone replacement therapy, the child's height increased and pituitary enlargement regressed to normal. Awareness of MRI appearance of pituitary hyperplasia in children with laboratory evidence of hypothyroidism might avoid misdiagnosis for pituitary tumor, which may also manifest as growth disorder, obviating unnecessary surgery. (orig.)

  9. Effect of primycin on growth-arrested cultures and cell integrity of Staphylococcus aureus.

    Science.gov (United States)

    Feiszt, Péter; Schneider, György; Emődy, Levente

    2017-06-01

    Bactericidal effect against non-dividing bacteria is a very advantageous, but rare characteristic among antimicrobial agents, mostly possessed by those affecting the cell membrane. These kinds of agents can kill bacterial cells without lysis. We assessed these characteristics on primycin, a topical anti-staphylococcal agent highly effective against prevalent multiresistant strains, as it also acts on the cell membrane. In time-kill studies, primycin preserved its bactericidal activity against growth-arrested Staphylococcus aureus cultures. The bactericidal action was slower against growth-arrested cultures compared to the exponentially growing ones to different extents depending on the manner of arrest. The bactericidal effect was less influenced by stringent response and by protein synthesis inhibition, proving that it does not depend on metabolic activity. In contrast, uncoupling of the membrane potential predominantly slowed, and low temperature almost stopped killing of bacteria. In consideration of published data, these facts suggest that the antibacterial action of primycin involves disrupting of the membrane potential, and is predominantly influenced by the membrane fluidity. Optical density measurements and transmission electron microscopy verified that primycin kills bacterial cells without lysis. These results reveal favorable characteristics of primycin and point to, and broaden the knowledge on its membrane-targeted effect.

  10. Growth Arrest Specific 2 Is Up-Regulated in Chronic Myeloid Leukemia Cells and Required for Their Growth

    OpenAIRE

    Haixia Zhou; Yue Ge; Lili Sun; Wenjuan Ma; Jie Wu; Xiuyan Zhang; Xiaohui Hu; Eaves, Connie J; Depei Wu; Yun Zhao

    2014-01-01

    Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML), the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2) regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form o...

  11. Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.

    Science.gov (United States)

    Suo, Guangli; Sadarangani, Anil; Tang, Wingchung; Cowan, Bryan D; Wang, Jean Y J

    2014-09-01

    Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.

  12. Modulation of medium pH by Caulobacter crescentus facilitates recovery from uranium-induced growth arrest.

    Science.gov (United States)

    Park, Dan M; Jiao, Yongqin

    2014-09-01

    The oxidized form of uranium [U(VI)] predominates in oxic environments and poses a major threat to ecosystems. Due to its ability to mineralize U(VI), the oligotroph Caulobacter crescentus is an attractive candidate for U(VI) bioremediation. However, the physiological basis for U(VI) tolerance is unclear. Here we demonstrated that U(VI) caused a temporary growth arrest in C. crescentus and three other bacterial species, although the duration of growth arrest was significantly shorter for C. crescentus. During the majority of the growth arrest period, cell morphology was unaltered and DNA replication initiation was inhibited. However, during the transition from growth arrest to exponential phase, cells with shorter stalks were observed, suggesting a decoupling between stalk development and the cell cycle. Upon recovery from growth arrest, C. crescentus proliferated with a growth rate comparable to that of a control without U(VI), although a fraction of these cells appeared filamentous with multiple replication start sites. Normal cell morphology was restored by the end of exponential phase. Cells did not accumulate U(VI) resistance mutations during the prolonged growth arrest, but rather, a reduction in U(VI) toxicity occurred concomitantly with an increase in medium pH. Together, these data suggest that C. crescentus recovers from U(VI)-induced growth arrest by reducing U(VI) toxicity through pH modulation. Our finding represents a unique U(VI) detoxification strategy and provides insight into how microbes cope with U(VI) under nongrowing conditions, a metabolic state that is prevalent in natural environments.

  13. High-density growth arrest in Ras-transformed cells: low Cdk kinase activities in spite of absence of p27Kip Cdk-complexes

    DEFF Research Database (Denmark)

    Groth, Anja; Willumsen, Berthe Marie

    2005-01-01

    The ras oncogene transforms immortalized, contact-inhibited non-malignant murine fibroblasts into cells that are focus forming, exhibit increased saturation density, and are malignant in suitable hosts. Here, we examined changes in cell cycle control complexes as normal and Ras-transformed cells...

  14. Necdin, a p53-target gene, is an inhibitor of p53-mediated growth arrest.

    Directory of Open Access Journals (Sweden)

    Julie Lafontaine

    Full Text Available In vitro, cellular immortalization and transformation define a model for multistep carcinogenesis and current ongoing challenges include the identification of specific molecular events associated with steps along this oncogenic pathway. Here, using NIH3T3 cells, we identified transcriptionally related events associated with the expression of Polyomavirus Large-T antigen (PyLT, a potent viral oncogene. We propose that a subset of these alterations in gene expression may be related to the early events that contribute to carcinogenesis. The proposed tumor suppressor Necdin, known to be regulated by p53, was within a group of genes that was consistently upregulated in the presence of PyLT. While Necdin is induced following p53 activation with different genotoxic stresses, Necdin induction by PyLT did not involve p53 activation or the Rb-binding site of PyLT. Necdin depletion by shRNA conferred a proliferative advantage to NIH3T3 and PyLT-expressing NIH3T3 (NIHLT cells. In contrast, our results demonstrate that although overexpression of Necdin induced a growth arrest in NIH3T3 and NIHLT cells, a growing population rapidly emerged from these arrested cells. This population no longer showed significant proliferation defects despite high Necdin expression. Moreover, we established that Necdin is a negative regulator of p53-mediated growth arrest induced by nutlin-3, suggesting that Necdin upregulation could contribute to the bypass of a p53-response in p53 wild type tumors. To support this, we characterized Necdin expression in low malignant potential ovarian cancer (LMP where p53 mutations rarely occur. Elevated levels of Necdin expression were observed in LMP when compared to aggressive serous ovarian cancers. We propose that in some contexts, the constitutive expression of Necdin could contribute to cancer promotion by delaying appropriate p53 responses and potentially promote genomic instability.

  15. Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest

    Institute of Scientific and Technical Information of China (English)

    Long-Zhu Li; Hong-Xia Deng; Wen-Zhu Lou; Xue-Yan Sun; Meng-Wan Song; Jing Tao; Bing-Xiu Xiao; Jun-Ming Guo

    2012-01-01

    AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

  16. Aspartate facilitates mitochondrial function, growth arrest and survival during doxorubicin exposure

    Science.gov (United States)

    Dornfeld, Ken; Madden, Michael; Skildum, Andrew; Wallace, Kendall B

    2015-01-01

    Genomic screens of doxorubicin toxicity in S. cerevisiae have identified numerous mutants in amino acid and carbon metabolism which express increased doxorubicin sensitivity. This work examines the effect of amino acid metabolism on doxorubicin toxicity. S. cerevisiae were treated with doxorubicin in combination with a variety of amino acid supplements. Strains of S. cerevisiae with mutations in pathways utilizing aspartate and other metabolites were examined for sensitivity to doxorubicin. S. cerevisiae cultures exposed to doxorubicin in minimal media showed significantly more toxicity than cultures exposed in rich media. Supplementing minimal media with aspartate, glutamate or alanine reduced doxorubicin toxicity. Cell cycle response was assessed by examining the budding pattern of treated cells. Cultures exposed to doxorubicin in minimal media arrested growth with no apparent cell cycle progression. Aspartate supplementation allowed cultures exposed to doxorubicin in minimal media to arrest after one division with a budding pattern and survival comparable to cultures exposed in rich media. Aspartate provides less protection from doxorubicin in cells mutant in either mitochondrial citrate synthase (CIT1) or NADH oxidase (NDI1), suggesting aspartate reduces doxorubicin toxicity by facilitating mitochondrial function. These data suggest glycolysis becomes less active and mitochondrial respiration more active following doxorubicin exposure. PMID:26317891

  17. Construction of a high-density linkage map and fine mapping of QTLs for growth and gonad related traits in blunt snout bream

    OpenAIRE

    Shi-Ming Wan; Hong Liu; Bo-Wen Zhao; Chun-Hong Nie; Wei-Min Wang; Ze-Xia Gao

    2017-01-01

    High-density genetic maps based on SNPs are essential for fine mapping loci controlling specific traits for fish species. Using restriction-site associated DNA tag sequencing (RAD-Seq) technology, we identified 42,784 SNPs evenly distributed across the Megalobrama amblycephala genome. Based on 2 parents and 187 intra-specific hybridization progenies, a total of 14,648 high-confidence SNPs were assigned to 24 consensus linkage groups (LGs) of maternal and paternal map. The total length of the ...

  18. p15(INK4b) in HDAC inhibitor-induced growth arrest.

    Science.gov (United States)

    Hitomi, Toshiaki; Matsuzaki, Youichirou; Yokota, Tomoya; Takaoka, Yuuki; Sakai, Toshiyuki

    2003-11-20

    Histone deacetylase (HDAC) inhibitors arrest human tumor cells at the G1 phase of the cell cycle and activate the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1). However, several studies have suggested the existence of a p21(WAF1/Cip1)-independent molecular pathway. We report here that HDAC inhibitors, trichostatin A (TSA) and sodium butyrate, activate the p15(INK4b) gene, a member of the INK4 gene family, through its promoter in HaCaT cells. Furthermore, we show that up-regulation of p15(INK4b) by TSA is associated with cell growth inhibition of HCT116 p21 (-/-) cells. Our findings suggest that p15(INK4b) is one of the important molecular targets of HDAC inhibitors.

  19. Noncoding RNA Gas5 Is a Growth Arrest and Starvation-Associated Repressor of the Glucocorticoid Receptor

    Science.gov (United States)

    Kino, Tomoshige; Hurt, Darrell E.; Ichijo, Takamasa; Nader, Nancy; Chrousos, George P.

    2010-01-01

    The availability of nutrients influences cellular growth and survival by affecting gene transcription. Glucocorticoids also influence gene transcription and have diverse activities on cell growth, energy expenditure, and survival. We found that the growth arrest-specific 5 (Gas5) noncoding RNA, which is abundant in cells whose growth has been arrested due to lack of nutrients or growth factors, sensitized cells to apoptosis by suppressing glucocorticoid-mediated induction of several responsive genes, including the one encoding cellular inhibitor of apoptosis 2. Gas5 bound to the DNA-binding domain of the glucocorticoid receptor (GR) by acting as a decoy “glucocorticoid response element (GRE)”, thus, competing with DNA GREs for binding to the GR. We conclude that Gas5 is a ribo-repressor of the GR, influencing cell survival and metabolic activities during starvation by modulating the transcriptional activity of the GR. PMID:20124551

  20. Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Yao Xiao-Jian

    2004-08-01

    Full Text Available Abstract Background The HIV-1 genome encodes a well-conserved accessory gene product, Vpr, that serves multiple functions in the retroviral life cycle, including the enhancement of viral replication in nondividing macrophages, the induction of G2 cell-cycle arrest, and the modulation of HIV-1-induced apoptosis. We previously reported the genetic selection of a panel of di-tryptophan (W-containing peptides capable of interacting with HIV-1 Vpr and inhibiting its cytostatic activity in Saccharomyces cerevisiae (Yao, X.-J., J. Lemay, N. Rougeau, M. Clément, S. Kurtz, P. Belhumeur, and E. A. Cohen, J. Biol. Chem. v. 277, p. 48816–48826, 2002. In this study, we performed a mutagenic analysis of Vpr to identify sequence and/or structural determinants implicated in the interaction with di-W-containing peptides and assessed the effect of mutations on Vpr-induced cytostatic activity in S. cerevisiae. Results Our data clearly shows that integrity of N-terminal α-helix I (17–33 and α-helix III (53–83 is crucial for Vpr interaction with di-W-containing peptides as well as for the protein-induced cytostatic effect in budding yeast. Interestingly, several Vpr mutants, mainly in the N- and C-terminal domains, which were previously reported to be defective for cell-cycle arrest or apoptosis in human cells, still displayed a cytostatic activity in S. cerevisiae and remained sensitive to the inhibitory effect of di-W-containing peptides. Conclusions Vpr-induced growth arrest in budding yeast can be effectively inhibited by GST-fused di-W peptide through a specific interaction of di-W peptide with Vpr functional domain, which includes α-helix I (17–33 and α-helix III (53–83. Furthermore, the mechanism(s underlying Vpr-induced cytostatic effect in budding yeast are likely to be distinct from those implicated in cell-cycle alteration and apoptosis in human cells.

  1. Glycogen synthesis correlates with androgen-dependent growth arrest in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gorin Frederic A

    2005-03-01

    Full Text Available Abstract Background Androgen withdrawal in normal prostate or androgen-dependent prostate cancer is associated with the downregulation of several glycolytic enzymes and with reduced glucose uptake. Although glycogen metabolism is known to regulate the intracellular glucose level its involvement in androgen response has not been studied. Methods We investigated the effects of androgen on glycogen phosphorylase (GP, glycogen synthase (GS and on glycogen accumulation in the androgen-receptor (AR reconstituted PC3 cell line containing either an empty vector (PC3-AR-V or vector with HPV-E7 (PC3-AR-E7 and the LNCaP cell line. Results Androgen addition in PC3 cells expressing the AR mimics androgen ablation in androgen-dependent prostate cells. Incubation of PC3-AR-V or PC3-AR-E7 cells with the androgen R1881 induced G1 cell cycle arrest within 24 hours and resulted in a gradual cell number reduction over 5 days thereafter, which was accompanied by a 2 to 5 fold increase in glycogen content. 24 hours after androgen-treatment the level of Glucose-6-P (G-6-P had increased threefold and after 48 hours the GS and GP activities increased twofold. Under this condition inhibition of glycogenolysis with the selective GP inhibitor CP-91149 enhanced the increase in glycogen content and further reduced the cell number. The androgen-dependent LNCaP cells that endogenously express AR responded to androgen withdrawal with growth arrest and increased glycogen content. CP-91149 further increased glycogen content and caused a reduction of cell number. Conclusion Increased glycogenesis is part of the androgen receptor-mediated cellular response and blockage of glycogenolysis by the GP inhibitor CP-91149 further increased glycogenesis. The combined use of a GP inhibitor with hormone therapy may increase the efficacy of hormone treatment by decreasing the survival of prostate cancer cells and thereby reducing the chance of cancer recurrence.

  2. Overexpressed active Notch1 induces cell growth arrest of HeLa cervical carcinoma cells.

    Science.gov (United States)

    Wang, L; Qin, H; Chen, B; Xin, X; Li, J; Han, H

    2007-01-01

    Human cervical carcinoma is one of the most common malignant tumors, but the mechanisms that orchestrate the multiple oncogenic insults required for initiation and progression are not clear. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis, but perturbed Notch signaling may contribute to tumorigenesis. We now show that Notch1 is detected in all cervical cancer, including advanced diseases. We also constitutively overexpressed active Notch1 in human cervical carcinoma to explore the effects of Notch1 signaling on human cervical carcinoma cell growth and to investigate the underlying molecular mechanisms. The signaling may participate in the development of human cervical carcinoma cells, but overexpressed active Notch1 inhibits their growth through induction of cell cycle arrest. Increased Notch1 signaling induced a downmodulation of human papillomavirus transcription through suppression of activator protein (AP)-1 activity by upregulation of c-Jun and the decreased expression of c-Fos. Thus, Notch1 signaling plays a key role and exerts dual effects, functioning in context-specific manner.

  3. Growth arrest and morphological changes triggered by emodin on Trypanosoma cruzi epimastigotes cultivated in axenic medium.

    Science.gov (United States)

    De Lima, Ana R; Noris-Suárez, Karem; Bretaña, Antonio; Contreras, Victor T; Navarro, Maria C; Pérez-Ybarra, Luis; Bubis, José

    2017-08-10

    Emodin is an anthraquinone obtained from Rheum palmatum rootstocks. Here we tested the cytotoxic effects of emodin on Trypanosoma cruzi epimastigotes, as well as the morphological changes that were induced by this compound in the parasite. Emodin was permeable and blocked in vitro cell division of T. cruzi epimastigotes in axenic medium, causing growth arrest in a dose-dependent but reversible manner. Emodin-exposed epimastigotes underwent duplication of organelles, such as the nucleus, kinetoplast and flagellum, but were incapable of completing cytokinesis. Neither elongation of the parasite body nor appearance of the regular longitudinal cleavage furrow was displayed, suggesting that emodin is most likely affecting components of the parasite cytoskeleton. Moreover, drug-treated parasites acquired alterations such as protuberances, folds and indentations on their membrane surface. Since emodin has been shown to be a potent protein kinase CK2 inhibitor, and we have previously described an association between tubulin and CK2 in T. cruzi epimastigotes (De Lima et al. Parasitology132, 511-523, 2006), we also measured the indirect effect of the drug on tubulin. Incubation of epimastigotes with axenic medium containing emodin hindered the endogenous phosphorylation of tubulin in whole-cell parasite extracts. All our results suggested that the parasite CK2 may be important for the maintenance of the morphology and for the regulation of mitosis-cytokinesis transition in T. cruzi epimastigotes. Copyright © 2017. Published by Elsevier B.V.

  4. Interaction of influenza virus NS1 protein with growth arrest-specific protein 8

    Directory of Open Access Journals (Sweden)

    Yu Mengbin

    2009-12-01

    Full Text Available Abstract NS1 protein is the only non-structural protein encoded by the influenza A virus, and it contributes significantly to disease pathogenesis by modulating many virus and host cell processes. A two-hybrid screen for proteins that interact with NS1 from influenza A yielded growth arrest-specific protein 8. Gas8 associated with NS1 in vitro and in vivo. Deletion analysis revealed that the N-terminal 260 amino acids of Gas8 were able to interact with NS1, and neither the RNA-binding domain nor the effector domain of NS1 was sufficient for the NS1 interaction. We also found that actin, myosin, and drebrin interact with Gas8. NS1 and β-actin proteins could be co-immunoprecipitated from extracts of transfected cells. Furthermore, actin and Gas8 co-localized at the plasma membrane. These results are discussed in relation to the possible functions of Gas8 protein and their relevance in influenza virus release.

  5. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Zhe Chen

    Full Text Available Nasopharyngeal carcinoma is a common malignant tumor in the head and neck. Because of frequent recurrence and distant metastasis which are the main causes of death, better treatment is needed. Indole-3-carbinol (I3C, a natural phytochemical found in the vegetables of the cruciferous family, shows anticancer effect through various signal pathways. I3C induces G1 arrest in NPC cell line with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1 and pRb. In vivo, nude mice receiving I3C protectively or therapeutically exhibited smaller tumors than control group after they were inoculated with nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb in preventive treatment group and drug treatment group both decreased compared with the control group. We conclude that I3C can inhibit the growth of NPC in vitro and in vivo by suppressing the expression of CDK and cyclin families. The drug was safe and had no toxic effects on normal tissues and organs.

  6. Antimicrobial Cream Formulated with Supercritical Carbon Dioxide Extract of Tuberose Flowers Arrests Growth of Staphylococcus aureus.

    Science.gov (United States)

    Ghosh, Probir Kumar; Bhattacharjee, Paramita; Das, Satadal

    2016-01-01

    Antimicrobial potency of herbal extracts is well known. The review of patents and research articles revealed that several herbal extracts have been employed in the formulation of topical products such as creams, exclusive of the cream reported in the present study. 0ur previous study has established antimicrobial potency of supercritical carbon dioxide extracts of tuberose flowers, better known for its sweet fragrance. The present work focuses on formulating a topical antimicrobial herbal cream with methyl eugenol (principal antimicrobial compound) rich - supercritical carbon dioxide extract of tuberose flowers, having good combination of phytochemical and antimicrobial potencies. Supercritical carbon dioxide parameters such as temperature, pressure and time were optimized using full factorial experimental design to obtain methyl eugenol-rich extracts. A cream was formulated using the extract having the best combination of phytochemical and antimicrobial potencies and was assayed further for in vitro antimicrobial potency; physiochemical and sensory properties. Two commercial antimicrobial cream samples were used as reference samples in the study. The extract obtained at 40°C, 10 MPa, 135 min at 1 L min-1 flow rate of gaseous C02 showed the best combination of phytochemical and antimicrobial potencies and was used for formulation of herbal creams. The cream formulated with 5% w/w of extract arrested growth of the common human skin pathogen Staphylococcus aureus and showed stable physiochemical properties and high sensory appeal for a year. The cream could be considered as a 'finished herbal product&' in compliance with the World Health 0rganization guidelines.

  7. Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle.

    Science.gov (United States)

    Zore, Gajanan B; Thakre, Archana D; Jadhav, Sitaram; Karuppayil, S Mohan

    2011-10-15

    Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole.

  8. Momordica cochinchinensis Spreng. seed extract suppresses breast cancer growth by inducing cell cycle arrest and apoptosis.

    Science.gov (United States)

    Zheng, Lei; Zhang, Yanmin; Liu, Yanping; Yang, Xiaoyan Ou; Zhan, Yingzhuan

    2015-10-01

    The herb Momordica cochinchinensis has been used for a variety of purposes, and been shown to have anti‑cancer properties. The present study assessed the potency and the underlying mechanisms of action of the ethyl acetate extract of seeds of Momordica cochinchinensis (ESMC2) on breast cancer cells. Therefore, the effects of ESMC2 on the cell viability, cell cycle and apoptosis of MDA‑MB‑231 cells were investigated. The results showed that ESMC2 exerted a marked growth inhibitory effect on the cells. Cell cycle arrest in G2 phase following treatment with ESMC2 was associated with a marked increase in the protein levels of cyclin B1, cyclin E and cyclin-dependent kinase 1 and a decrease in cyclin D1 expression. In addition, ESMC2 dose‑dependently induced cell apoptosis, which was mediated via upregulation of the apoptosis-associated proteins p53, B-cell lymphoma 2 (Bcl‑2)‑associated X protein, Bcl-2 homologous antagonist killer and Bcl-2-associated death promoter expression, as well as downregulation of nuclear factor kappa B, Bcl‑2 and myeloid cell leukemia‑1. Furthermore, the activation of extracellular signal-regulated kinase 1/2, p38, c-Jun N-terminal kinase (JNK) and Akt phosphorylation were decreased by ESMC2 in a dose‑dependent manner, indicating that ESMC2 exerted its effects via the mitogen-activated protein kinase/JNK pathway. Furthermore, nude mouse xenotransplant models were used to evaluate the tumor growth inhibitory effects of ESMC2. The possible chemical components of ESMC2 were analyzed by gas chromatography-mass spectrometry, and 12 compounds were detected from the major peaks based on the similarity index with entries of a compound database. The results of the present study may aid in the development of novel therapies for breast cancer.

  9. Controlled growth of high-density CdS and CdSe nanorod arrays on selective facets of two-dimensional semiconductor nanoplates

    KAUST Repository

    Wu, Xue-Jun

    2016-03-14

    The rational synthesis of hierarchical three-dimensional nanostructures with specific compositions, morphologies and functionalities is important for applications in a variety of fields ranging from energy conversion and electronics to biotechnology. Here, we report a seeded growth approach for the controlled epitaxial growth of three types of hierarchical one-dimensional (1D)/two-dimensional (2D) nanostructures, where nanorod arrays of II-VI semiconductor CdS or CdSe are grown on the selective facets of hexagonal-shaped nanoplates, either on the two basal facets of the nanoplate, or on one basal facet, or on the two basal facets and six side facets. The seed engineering of 2D hexagonal-shaped nanoplates is the key factor for growth of the three resulting types of 1D/2D nanostructures. The wurtzite- and zinc-blende-type polymorphs of semiconductors are used to determine the facet-selective epitaxial growth of 1D nanorod arrays, resulting in the formation of different hierarchical three-dimensional (3D) nanostructures. © 2016 Macmillan Publishers Limited. All rights reserved.

  10. Controlled growth of high-density CdS and CdSe nanorod arrays on selective facets of two-dimensional semiconductor nanoplates.

    Science.gov (United States)

    Wu, Xue-Jun; Chen, Junze; Tan, Chaoliang; Zhu, Yihan; Han, Yu; Zhang, Hua

    2016-05-01

    The rational synthesis of hierarchical three-dimensional nanostructures with specific compositions, morphologies and functionalities is important for applications in a variety of fields ranging from energy conversion and electronics to biotechnology. Here, we report a seeded growth approach for the controlled epitaxial growth of three types of hierarchical one-dimensional (1D)/two-dimensional (2D) nanostructures, where nanorod arrays of II-VI semiconductor CdS or CdSe are grown on the selective facets of hexagonal-shaped nanoplates, either on the two basal facets of the nanoplate, or on one basal facet, or on the two basal facets and six side facets. The seed engineering of 2D hexagonal-shaped nanoplates is the key factor for growth of the three resulting types of 1D/2D nanostructures. The wurtzite- and zinc-blende-type polymorphs of semiconductors are used to determine the facet-selective epitaxial growth of 1D nanorod arrays, resulting in the formation of different hierarchical three-dimensional (3D) nanostructures.

  11. Controlled growth of high-density CdS and CdSe nanorod arrays on selective facets of two-dimensional semiconductor nanoplates

    Science.gov (United States)

    Wu, Xue-Jun; Chen, Junze; Tan, Chaoliang; Zhu, Yihan; Han, Yu; Zhang, Hua

    2016-05-01

    The rational synthesis of hierarchical three-dimensional nanostructures with specific compositions, morphologies and functionalities is important for applications in a variety of fields ranging from energy conversion and electronics to biotechnology. Here, we report a seeded growth approach for the controlled epitaxial growth of three types of hierarchical one-dimensional (1D)/two-dimensional (2D) nanostructures, where nanorod arrays of II-VI semiconductor CdS or CdSe are grown on the selective facets of hexagonal-shaped nanoplates, either on the two basal facets of the nanoplate, or on one basal facet, or on the two basal facets and six side facets. The seed engineering of 2D hexagonal-shaped nanoplates is the key factor for growth of the three resulting types of 1D/2D nanostructures. The wurtzite- and zinc-blende-type polymorphs of semiconductors are used to determine the facet-selective epitaxial growth of 1D nanorod arrays, resulting in the formation of different hierarchical three-dimensional (3D) nanostructures.

  12. Fibroblasts from long-lived Snell dwarf mice are resistant to oxygen-induced in vitro growth arrest

    DEFF Research Database (Denmark)

    Maynard, Scott P; Miller, Richard A

    2006-01-01

    Snell dwarf mice live longer than controls, and show lower age-adjusted rates of lethal neoplastic diseases. Fibroblast cells from adult dwarf mice are resistant to the lethal effects of oxidative and nonoxidative stresses, including the carcinogen methyl methanesulfonate. We now report that dwarf...... in skin fibroblasts by the hormonal milieu of the Snell dwarf lead to resistance to multiple forms of injury, including the oxidative damage that contributes to growth arrest in vitro and neoplasia in intact mice....

  13. Saturation and High Density QCD

    OpenAIRE

    Mueller, A. H.

    2005-01-01

    Recent progress in understanding general properties of high energy scattering near the unitarity limit, where high density gluon components of the wavefunction are dominant, is reviewed. The similarity of the QCD problem and that of reaction-diffusion processes in statistical physics is emphasized. The energy dependence of the saturation momentum and the status of geometric scaling are discussed.

  14. High-density multicore fibers

    DEFF Research Database (Denmark)

    Takenaga, K.; Matsuo, S.; Saitoh, K.;

    2016-01-01

    High-density single-mode multicore fibers were designed and fabricated. A heterogeneous 30-core fiber realized a low crosstalk of −55 dB. A quasi-single-mode homogeneous 31-core fiber attained the highest core count as a single-mode multicore fiber....

  15. SUMO modification of Stra13 is required for repression of cyclin D1 expression and cellular growth arrest.

    Directory of Open Access Journals (Sweden)

    Yaju Wang

    Full Text Available Stra13, a basic helix-loop-helix (bHLH transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G(1 cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1, attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G(1/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.

  16. Growth arrest and a persister state enable resistance to osmotic shock and facilitate dissemination of Vibrio cholerae.

    Science.gov (United States)

    Silva-Valenzuela, Cecilia A; Lazinski, David W; Kahne, Shoshanna C; Nguyen, Y; Molina-Quiroz, Roberto C; Camilli, Andrew

    2017-07-25

    Vibrio cholerae is a water-borne bacterial pathogen and causative agent of cholera. Although V. cholerae is a halophile, it can survive in fresh water, and this has a major role in cholera epidemics through consumption of contaminated water and subsequent fecal-oral spread. After dissemination from humans back into fresh water, V. cholerae encounters limited nutrient availability and an abrupt drop in conductivity but little is known about how V. cholerae adapts to, and survives in this environment. In this work, by abolishing or altering the expression of V. cholerae genes in a high-throughput manner, we observed that many osmotic shock tolerant mutants exhibited slowed or arrested growth, and/or generated a higher proportion of persister cells. In addition, we show that growth-arrested V. cholerae, including a persister subpopulation, are generated during infection of the intestinal tract and together allow for the successful dissemination to fresh water. Our results suggest that growth-arrested and persister subpopulations enable survival of V. cholerae upon shedding to the aquatic environment.The ISME Journal advance online publication, 25 July 2017; doi:10.1038/ismej.2017.121.

  17. Growth arrest specific 2 is up-regulated in chronic myeloid leukemia cells and required for their growth.

    Directory of Open Access Journals (Sweden)

    Haixia Zhou

    Full Text Available Although the generation of BCR-ABL is the molecular hallmark of chronic myeloid leukemia (CML, the comprehensive molecular mechanisms of the disease remain unclear yet. Growth arrest specific 2 (GAS2 regulates multiple cellular functions including cell cycle, apoptosis and calpain activities. In the present study, we found GAS2 was up-regulated in CML cells including CD34+ progenitor cells compared to their normal counterparts. We utilized RNAi and the expression of dominant negative form of GAS2 (GAS2DN to target GAS2, which resulted in calpain activity enhancement and growth inhibition of both K562 and MEG-01 cells. Targeting GAS2 also sensitized K562 cells to Imatinib mesylate (IM. GAS2DN suppressed the tumorigenic ability of MEG-01 cells and impaired the tumour growth as well. Moreover, the CD34+ cells from CML patients and healthy donors were transduced with control and GAS2DN lentiviral vectors, and the CD34+ transduced (YFP+ progeny cells (CD34+YFP+ were plated for colony-forming cell (CFC assay. The results showed that GAS2DN inhibited the CFC production of CML cells by 57±3% (n = 3, while affected those of normal hematopoietic cells by 31±1% (n = 2. Next, we found the inhibition of CML cells by GAS2DN was dependent on calpain activity but not the degradation of beta-catenin. Lastly, we generated microarray data to identify the differentially expressed genes upon GAS2DN and validated that the expression of HNRPDL, PTK7 and UCHL5 was suppressed by GAS2DN. These 3 genes were up-regulated in CML cells compared to normal control cells and the growth of K562 cells was inhibited upon HNRPDL silence. Taken together, we have demonstrated that GAS2 is up-regulated in CML cells and the inhibition of GAS2 impairs the growth of CML cells, which indicates GAS2 is a novel regulator of CML cells and a potential therapeutic target of this disease.

  18. Embedded Nanowire Network Growth and Node Device Fabrication for GaAs-Based High-Density Hexagonal Binary Decision Diagram Quantum Circuits

    Science.gov (United States)

    Tamura, Takahiro; Tamai, Isao; Kasai, Seiya; Sato, Taketomo; Hasegawa, Hideki; Hashizume, Tamotsu

    2006-04-01

    The basic feasibility of constructing hexagonal binary decision diagram (BDD) quantum circuits on GaAs-based selectively grown (SG) nanowires was investigated from viewpoints of electrical connections through embedded nanowires and electrical uniformity of devices formed on nanowires. For this, - and -oriented nanowires and hexagonal network structures combining these nanowires were formed on (001) GaAs substrates by selective molecular beam epitaxy (MBE) growth. The width and vertical position of the nanowires could be controlled by growth conditions for both - and -directions. By current-voltage (I-V) measurements, good electrical connection was confirmed at the node point where vertical alignment of embedded GaAs nanowire pieces was found to be important. SG quantum wire (QWR) switches formed on the nanowires showed good gate control over a wide temperature range with clear conductance quantization at low temperatures. Good device uniformities were obtained on the test chips, providing a good prospect for future integration. BDD node devices using SG QWR switches showed clear path switching characteristics. Estimated power-delay product values were very small, confirming the feasibility of ultra low-power operation of future circuits.

  19. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease.

    Directory of Open Access Journals (Sweden)

    Wesley R Lewis

    2016-07-01

    Full Text Available Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400. While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8. GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC protein 4 (DRC4 where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR to generate one of these human missense

  20. Quercetin induces growth arrest through activation of FOXO1 transcription factor in EGFR-overexpressing oral cancer cells.

    Science.gov (United States)

    Huang, Chun-Yin; Chan, Chien-Yi; Chou, I-Tai; Lien, Chia-Hsien; Hung, Hsiao-Chi; Lee, Ming-Fen

    2013-09-01

    The squamous cell carcinomas of the head and neck (SCCHNs) with aberrant epidermal growth factor receptor (EGFR) signaling are often associated with poor prognosis and low survival. Therefore, efficient inhibition of the EGFR signaling could intervene with the development of malignancy. Quercetin appears to be antitumorigenesis, but the underlying mechanism remains unclear in oral cancer. Fork-head box O (FOXO) transcription factors, Akt downstream effectors, are important regulators of cell growth. Here, we hypothesized that FOXO1 might be crucial in quercetin-induced growth inhibition in EGFR-overexpressing oral cancer. Quercetin treatment suppressed cell growth by inducing G2 arrest and apoptosis in EGFR-overexpressing HSC-3 and TW206 oral cancer cells. Quercetin inhibited EGFR/Akt activation with a concomitant induction of FOXO1 activation. FOXO1 knockdown attenuated quercetin-induced p21 and FasL expression and subsequent G2 arrest and apoptosis, respectively. Likewise, quercetin suppressed tumor growth in HSC-3 xenograft mice. Taken together, our data indicate that quercetin is an effective anticancer agent and that FOXO1 is crucial in quercetin-induced growth suppression in EGFR-overexpressing oral cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. High density fluoride glass calorimeter

    Science.gov (United States)

    Xie, Q.; Scheltzbaum, J.; Akgun, U.

    2014-04-01

    The unprecedented radiation levels in current Large Hadron Collider runs, and plans to even increase the luminosity creates a need for new detector technologies to be investigated. Quartz plates to replace the plastic scintillators in current LHC calorimeters have been proposed in recent reports. Quartz based Cherenkov calorimeters can solve the radiation damage problem, however light production and transfer have proven to be challenging. This report summarizes the results from a computational study on the performance of a high-density glass calorimeter. High-density, scintillating, fluoride glass, CHG3, was used as the active material. This glass has been developed specifically for hadron collider experiments, and is known for fast response time, in addition to high light yield. Here, the details of a Geant4 model for a sampling calorimeter prototype with 20 layers, and its hadronic as well as electromagnetic performances are reported.

  2. Overexpression of a novel gene, Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    MCM10 protein is an essential replication factor involved in the initiation of DNA replication. A mcm10 mutant (mcm10-1) of budding yeast shows a growth arrest at 37℃. In the present work, we have isolated a mcm10-1 suppressor strain, which grows at 37℃. Interestingly, this mcm10-1 suppressor undergoes cell cycle arrest at 14℃. A novel gene, YLR003c, is identified by high-copy complementation of this suppressor. We called it as Cmsl (Complementation of Mcm 10 Suppressor). Furthermore, the experiments of transformation show that cells of mcm10-1 suppressor with high-copy plasmid but not low-copy plasmid grow at 14℃, indicating that overexpression of Cmsl can rescue the growth arrest of this mcm10 suppressor at non-permissive temperature. These results suggest that CMS1 protein may functionally interact with MCM10 protein and play a role in the regulation of DNA replication and cell cycle control.

  3. Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest

    Directory of Open Access Journals (Sweden)

    Qiusheng Lan

    2015-08-01

    Full Text Available The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2 apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.

  4. Methyl Sartortuoate Inhibits Colon Cancer Cell Growth by Inducing Apoptosis and G2/M-Phase Arrest.

    Science.gov (United States)

    Lan, Qiusheng; Li, Shoufeng; Lai, Wei; Xu, Heyang; Zhang, Yang; Zeng, Yujie; Lan, Wenjian; Chu, Zhonghua

    2015-08-17

    The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.

  5. Sequential signaling cascade of IL-6 and PGC-1α is involved in high glucose-induced podocyte loss and growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Il; Park, Soo Hyun, E-mail: parksh@chonnam.ac.kr

    2013-06-14

    Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.

  6. High density matter at RHIC

    Indian Academy of Sciences (India)

    Thomas S Ullrich

    2004-02-01

    QCD predicts a phase transition between hadronic matter and a quark-gluon plasma at high energy density. The relativistic heavy ion collider (RHIC) at Brookhaven National Laboratory is a new facility dedicated to the experimental study of matter under extreme conditions. Already the first round of experimental results at RHIC indicated that the conditions to create a new state of matter are indeed reached in the collisions of heavy nuclei. Studies of particle spectra and their correlations at low transverse momenta provide evidence of strong pressure gradients in the highly interacting dense medium and hint that we observe a system in thermal equilibrium. Recent runs with high statistics allow us to explore the regime of hard-scattering processes where the suppression of hadrons at large transverse momentum, and quenching of di-jets are observed thus providing further evidence for extreme high density matter created in collisions at RHIC.

  7. The Effects of Ethanol and Strontium on Growth and Development of Two-Cell Arrested Mouse Embryos

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Darabi

    2012-01-01

    Full Text Available Background: Arresting at a certain stage of development like the two-cell stage could be one of the causes of infertility. The aim of this study is to evaluate the effects of ethanol and strontium on growth and development of mice embryos arrested at the two-cell stage.Materials and Methods: In this experimental study, female mice were coupled with a male following superovulation. Positive vaginal plug mice were sacrificed 48 hours after human chorionic gonadotropin (hCG injection. Two-cell embryos were transferred to M16 medium and divided to four groups. The first control group was incubated without any exposure to low temperatures. Groups 2, 3 and 4 were exposed to 4°C for 24 hours. The second control group was incubated immediately, while the third and fourth groups were exposed to 10 mM strontium for five minutes and 0.1% ethanol for a further five minutes. Growth rate and developmental parameters of embryos were analyzed by one-way ANOVA. The significant difference between the groups was determined by Post Hoc.Results: The data shows that developmental rate is decreased significantly by 4°C exposure. The mean percentage of degenerated embryo was significantly different between groups but the mean cleavage rate was not significantly different. The mean percent of morula, blastocyst and hatched blastocyst formation were significantly different between groups during a 120 hours study post hCG injection.Conclusion: The effect of strontium and ethanol on arrested two-cell embryos had no significant effect on the mean percentage of morula, but ethanol treatment significantly increased the percentage of blastocyst and hatched blastocyst formation compared to strontium.

  8. HipA-triggered growth arrest and β-lactam tolerance in Escherichia coli are mediated by RelA-dependent ppGpp synthesis.

    Science.gov (United States)

    Bokinsky, Gregory; Baidoo, Edward E K; Akella, Swetha; Burd, Helcio; Weaver, Daniel; Alonso-Gutierrez, Jorge; García-Martín, Héctor; Lee, Taek Soon; Keasling, Jay D

    2013-07-01

    Persistence is a phenomenon whereby a subpopulation of bacterial cells enters a transient growth-arrested state that confers antibiotic tolerance. While entrance into persistence has been linked to the activities of toxin proteins, the molecular mechanisms by which toxins induce growth arrest and the persistent state remain unclear. Here, we show that overexpression of the protein kinase HipA in Escherichia coli triggers growth arrest by activating synthesis of the alarmone guanosine tetraphosphate (ppGpp) by the enzyme RelA, a signal typically associated with amino acid starvation. We further demonstrate that chemically suppressing ppGpp synthesis with chloramphenicol relieves inhibition of DNA replication initiation and RNA synthesis in HipA-arrested cells and restores vulnerability to β-lactam antibiotics. HipA-arrested cells maintain glucose uptake and oxygen consumption and accumulate amino acids as a consequence of translational inhibition. We harness the active metabolism of HipA-arrested cells to provide a bacteriophage-resistant platform for the production of biotechnologically relevant compounds, which may represent an innovative solution to the costly problem of phage contamination in industrial fermentations.

  9. The Mobile bypass Signal Arrests Shoot Growth by Disrupting Shoot Apical Meristem Maintenance, Cytokinin Signaling, and WUS Transcription Factor Expression.

    Science.gov (United States)

    Lee, Dong-Keun; Parrott, David L; Adhikari, Emma; Fraser, Nisa; Sieburth, Leslie E

    2016-07-01

    The bypass1 (bps1) mutant of Arabidopsis (Arabidopsis thaliana) produces a root-sourced compound (the bps signal) that moves to the shoot and is sufficient to arrest growth of a wild-type shoot; however, the mechanism of growth arrest is not understood. Here, we show that the earliest shoot defect arises during germination and is a failure of bps1 mutants to maintain their shoot apical meristem (SAM). This finding suggested that the bps signal might affect expression or function of SAM regulatory genes, and we found WUSCHEL (WUS) expression to be repressed in bps1 mutants. Repression appears to arise from the mobile bps signal, as the bps1 root was sufficient to rapidly down-regulate WUS expression in wild-type shoots. Normally, WUS is regulated by a balance between positive regulation by cytokinin (CK) and negative regulation by CLAVATA (CLV). In bps1, repression of WUS was independent of CLV, and, instead, the bps signal down-regulates CK responses. Cytokinin treatment of bps1 mutants restored both WUS expression and activity, but only in the rib meristem. How the bps signal down-regulates CK remains unknown, though the bps signal was sufficient to repress expression of one CK receptor (AHK4) and one response regulator (AHP6). Together, these data suggest that the bps signal pathway has the potential for long-distance regulation through modification of CK signaling and altering gene expression. © 2016 American Society of Plant Biologists. All Rights Reserved.

  10. Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Fata, Jimmie E.; Martin, Katherine J.; Yaswen, Paul; Bissell, Mina J.

    2009-06-03

    PTEN is a dual function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two non-malignant human mammary epithelial cell lines (HMECs) that form polarized, growth-arrested structures (acini) when cultured in 3-dimensional laminin-rich extracellular matrix gels (3D lrECM). As acini begin to form, PTEN accumulates in both the cytoplasm, and at cell-cell contacts where it colocalizes with E-cadherin/{beta}-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function-blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in SKBR3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in 3D lrECM indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus appears to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells.

  11. The mitogen-activated protein kinase pathway mediates growth arrest or E1A-dependent apoptosis in SKBR3 human breast cancer cells.

    Science.gov (United States)

    Blagosklonny, M V

    1998-11-09

    Previously, we have shown that phorbol ester (PMA) induces p21(WAF1/CIP1)-dependent growth arrest in SKBr3 breast cancer and LNCaP prostate cancer cells. Here, I demonstrate that inhibition of Raf-1 kinase by dominant-negative Raf-1 or pharmacological depletion of Raf-1 prevented PMA-mediated induction of p21(WAF1/CIP1). Similarly, PD98059, a specific inhibitor of MEK, abolished p21(WAF1/CIP1) induction and PMA-induced growth arrest. Like PMA, the H-ras oncogene, another activator of the Raf-1/MEK/MAPK pathway, transactivated p21(WAF1/CIP1) in SKBr3 cells. I further investigated PMA-induced growth arrest following infection of SKBr3 cells with 12S E1A-expressing adenovirus. Although high levels of E1A oncoprotein prevented both PMA-induced p21(WAF1/CIP1) and growth arrest, smaller amounts of E1A abrogated growth arrest without down-regulation of p21(WAF1/CIP1). Therefore, E1A can stimulate proliferation downstream of p21(WAF1/CIP1). Albeit less effective than full activity, either Rb- or p300-binding activity of E1A was sufficient for the abrogation of PMA-mediated growth arrest. E1A-driven proliferation of PMA-treated SKBr3 cells was accompanied by apoptosis. New therapeutic approaches can be envisioned that would utilize stimulation of the Raf-1/MEK/MAPK pathway to inhibit growth of PMA-sensitive cancer cells.

  12. Berberine inhibits growth and induces G1 arrest and apoptosis in human cholangiocarcinoma QBC939 cells.

    Science.gov (United States)

    He, Wei; Wang, Bin; Zhuang, Yun; Shao, Dong; Sun, Kewen; Chen, Jianping

    2012-01-01

    The chemotherapeutic approach using non-toxic natural products may be one of the strategies for the management of the cholangiocarcinoma. Here we report that in vitro treatment of human cholangiocarcinoma QBC939 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability and induced cell death in a dose-dependent manner, which was associated with an increase in G1 arrest. Our western blot analysis showed that berberine-induced G1 cell cycle arrest was mediated through the increased expression of cyclin-dependent kinase inhibitors (Cdki) proteins (Cip1/p21 and Kip1/p27); a simultaneous decrease in Cdk2 and Cdk4 and cyclins D1, and reduced activity of the Cyclins-Cdk complex. In additional studies, treatment of QBC939 cells with different concentrations (10, 40, 80 μM) of berberine for 48 h resulted in a significant dose-dependent increase in apoptosis compared to the non-berberine-treated control, which was associated with an increased expression of pro-apoptotic protein Bax and decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Together, this study for the first time identified berberine as a chemotherapeutic agent against human cholangiocarcinoma cells QBC939 cells in vitro. Further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of cholangiocarcinoma.

  13. Ethyl acetate extract of Squilla oratoria suppresses growth of HepG2 cells by inducing S phase arrest

    Directory of Open Access Journals (Sweden)

    Xiangwei Qi

    2013-08-01

    Full Text Available Objective: The oceans and seas are a rich source of organisms from which anti-cancer drugs can be isolated and developed. Marine organisms have been screened in our laboratory, and organic solvent extracts of Squilla oratoria (ESO have been shown to possess cytostatic effects on cancer cell lines of diverse origins. To explore the underlying mechanisms, the growth inhibition by ESO was investigated in the present study. Methods: Human hepatocellular carcinoma (HCC derived cells (HepG2 were used. The cells were challenged with ESO, cell cycle profile was assayed, and level of proliferating cell nuclear antigen (PCNA expression and that of cyclin D1 and cyclin A were evaluated with flow cytomtery. The in vivo antitumor effect of ESO was tested in nude mouse xenografts. PCNA expression was evaluated immunohistochemically in nude mouse xenograft tissues. Results: With the increase in dose of injected ESO, expression of PCNA by human HCC xenografts increased. ESO inhibited the growth of human HCC HepG2 cells both in vitro and in vivo. The effect was correlated with arrest of the cell cycle in S phase. Expression of PCNA, which is a cell-cycle regulator that promotes S phase entry, was elevated in both cell lines and xenografts whereas that of cyclins that promote M phase entry was down-regulated by exposure to ESO. Conclusion: Growth inhibition was explained by arrest of the cell cycle in S phase and down-regulation of molecules that promote cells to enter S phase. [J Exp Integr Med 2013; 3(4.000: 313-322

  14. δ-tocotrienol induces human bladder cancer cell growth arrest, apoptosis and chemosensitization through inhibition of STAT3 pathway.

    Directory of Open Access Journals (Sweden)

    Changxiao Ye

    Full Text Available Vitamin E intake has been implicated in reduction of bladder cancer risk. However, the mechanisms remain elusive. Here we reported that δ-tocotrienol (δ-T3, one of vitamin E isomers, possessed the most potent cytotoxic capacity against human bladder cancer cells, compared with other Vitamin E isomers. δ-T3 inhibited cancer cell proliferation and colonogenicity through induction of G1 phase arrest and apoptosis. Western blotting assay revealed that δ-T3 increased the expression levels of cell cycle inhibitors (p21, p27, pro-apoptotic protein (Bax and suppressed expression levels of cell cycle protein (Cyclin D1, anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1, resulting in the Caspase-3 activation and cleavage of PARP. Moreover, the δ-T3 treatment inhibited ETK phosphorylation level and induced SHP-1 expression, which was correlated with downregulation of STAT3 activation. In line with this, δ-T3 reduced the STAT3 protein level in nuclear fraction, as well as its transcription activity. Knockdown of SHP-1 partially reversed δ-T3-induced cell growth arrest. Importantly, low dose of δ-T3 sensitized Gemcitabine-induced cytotoxic effects on human bladder cancer cells. Overall, our findings demonstrated, for the first time, the cytotoxic effects of δ-T3 on bladder cancer cells and suggest that δ-T3 might be a promising chemosensitization reagent for Gemcitabine in bladder cancer treatment.

  15. Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

    Directory of Open Access Journals (Sweden)

    Raja Kumar Vadivelu

    2012-01-01

    Full Text Available Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05. Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC.

  16. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  17. An optimization protocol for Swiss 3T3 feeder cell growth-arrest by Mitomycin C dose-to-volume derivation strategy.

    Science.gov (United States)

    Chugh, Rishi Man; Chaturvedi, Madhusudan; Yerneni, Lakshmana Kumar

    2017-04-01

    Feeder cell functionality following growth-arrest with the cost-effective Mitomycin C vis-à-vis irradiation is controversial due to several methodological variables reported. Earlier, we demonstrated variability in growth arrested Swiss 3T3 feeder cell life-span following titration of feeder cell densities with Mitomycin C concentrations which led to the derivation of doses per cell. Alternatively, to counter the unexpected feeder regrowth at high exposure cell density, we proposed titration of a fixed density with arithmetically derived volumes of Mitomycin C solution that corresponded to permutations of specific concentrations and doses per cell. We now describe an experimental procedure of inducing differential feeder cell growth-arrest by titrating with such volumes and validating the best feeder batch through target cell growth assessment. A safe cell density of Swiss 3T3 tested for the exclusion of Mitomycin C resistant variants was titrated with a range of volumes of a Mitomycin C solution. The differentially growth-arrested feeder batches generated were tested for short-term and long-term viability and human epidermal keratinocyte growth supporting ability. The feeder cell extinction rate was directly proportional to the volume of Mitomycin C solution within a given concentration per se. The keratinocyte colony forming efficiency and the overall growth in mass cultures were maximal with a median extinction rate produced by an intermediate volume, while the faster and slower extinction rates by high and low volumes, respectively, were suboptimal. The described method could counter the inadequacies of growth-arrest with Mitomycin C.

  18. Differential regulation of vitamin D receptor expression in distinct leukemic cell lines upon phorbol ester-induced growth arrest

    Directory of Open Access Journals (Sweden)

    Folgueira M.A.A.K.

    2000-01-01

    Full Text Available A close correlation between vitamin D receptor (VDR abundance and cell proliferation rate has been shown in NIH-3T3 fibroblasts, MCF-7 breast cancer and in HL-60 myeloblastic cells. We have now determined if this association occurs in other leukemic cell lines, U937 and K562, and if VDR content is related to c-myc expression, which is also linked to cell growth state. Upon phorbol myristate acetate (PMA treatment, cells from the three lineages (HL-60, U937 and K562 differentiated and expressed specific surface antigens. All cell lines analyzed were growth inhibited by PMA and the doubling time was increased, mainly due to an increased fraction of cells in the G0/G1 phase, as determined by flow cytometry measurements of incorporated bromodeoxyuridine and cell DNA content. C-myc mRNA expression was down-regulated and closely correlated to cell growth arrest. However, VDR expression in leukemic cell lines, as determined by immunofluorescence and Northern blot assays, was not consistently changed upon inhibition of cell proliferation since VDR levels were down-regulated only in HL-60 cells. Our data suggest that VDR expression cannot be explained simply as a reflection of the leukemic cell growth state.

  19. NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through HDAC6 Inhibition in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jih-Tung Pai

    2015-05-01

    Full Text Available Disrupting lung tumor growth via histone deacetylases (HDACs inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90 mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA, a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4.

  20. Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis.

    Science.gov (United States)

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E; Gassmann, Walter; Schroeder, Julian I

    2012-12-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor-nucleotide binding-Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid-induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest.

  1. Involvement of MINK, a Ste20 Family Kinase, in Ras Oncogene-Induced Growth Arrest in Human Ovarian Surface Epithelial Cells

    NARCIS (Netherlands)

    Nicke, B.; Bastien, J.; Khanna, S.J.; Warne, P.H.; Cowling, V.; Cook, S.J.; Peters, G.; Delpuech, O.; Schulze, A.; Berns, K.; Mullenders, J.; Beijersbergen, R.L.; Bernards, R.A.; Ganesan, T.S.; Downward, J.; Hancock, D.C.

    2005-01-01

    The ability of activated Ras to induce growth arrest of human ovarian surface epithelial (HOSE) cells via induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 has been used to screen for Ras pathway signaling components using a library of RNA interference (RNAi) vectors targeting the kino

  2. B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B lymphoma cells involve cyclic AMP and Epac proteins

    NARCIS (Netherlands)

    Grandoch, Maria; de Jesus, Maider Lopez; Weernink, Paschal A. Oude; Weber, Artur-Aron; Jakobs, Karl H.; Schmidt, Martina

    2009-01-01

    Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte homeostasis and immune function. In immature B cells, ligation of the BCR promotes growth arrest and apoptosis, and BCR-driven balancing between pro-apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and antia

  3. Opposing roles of C/EBPbeta and AP-1 in the control of fibroblast proliferation and growth arrest-specific gene expression

    DEFF Research Database (Denmark)

    Gagliardi, Mark; Maynard, Scott; Miyake, Tetsuaki

    2003-01-01

    Chicken embryo fibroblasts (CEF) express several growth arrest-specific (GAS) gene products in G0. In contact-inhibited cells, the expression of the most abundant of these proteins, the p20K lipocalin, is activated at the transcriptional level by C/EBPbeta. In this report, we describe the role of...

  4. Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility

    Directory of Open Access Journals (Sweden)

    Lazo John S

    2010-05-01

    Full Text Available Abstract Background Protein kinase D (PKD has been implicated in a wide range of cellular processes and pathological conditions including cancer. However, targeting PKD therapeutically and dissecting PKD-mediated cellular responses remains difficult due to lack of a potent and selective inhibitor. Previously, we identified a novel pan-PKD inhibitor, CID755673, with potency in the upper nanomolar range and high selectivity for PKD. In an effort to further enhance its selectivity and potency for potential in vivo application, small molecule analogs of CID755673 were generated by modifying both the core structure and side-chains. Results After initial activity screening, five analogs with equal or greater potencies as CID755673 were chosen for further analysis: kb-NB142-70, kb-NB165-09, kb-NB165-31, kb-NB165-92, and kb-NB184-02. Our data showed that modifications to the aromatic core structure in particular significantly increased potency while retaining high specificity for PKD. When tested in prostate cancer cells, all compounds inhibited PMA-induced autophosphorylation of PKD1, with kb-NB142-70 being most active. Importantly, these analogs caused a dramatic arrest in cell proliferation accompanying elevated cytotoxicity when applied to prostate cancer cells. Cell migration and invasion were also inhibited by these analogs with varying potencies that correlated to their cellular activity. Conclusions Throughout the battery of experiments, the compounds kb-NB142-70 and kb-NB165-09 emerged as the most potent and specific analogs in vitro and in cells. These compounds are undergoing further testing for their effectiveness as pharmacological tools for dissecting PKD function and as potential anti-cancer agents in the treatment of prostate cancer.

  5. Cell Growth Arrest Mediated by STAT Proteins in Breast Cancer Cells

    Science.gov (United States)

    1998-07-01

    pepstatin, and aprotinin (1 (Xg/ml each). Whole cell extracts were immediately subjected to electromobility shift assay. Preparation of membrane and...activation on the cytosol fraction (STAT protein) concentration. Electromobility shift assay (EMSA) The sample after in vitro activation (3 ul) (1 [il...transcription; EGF, epidermal growth factor; NGF, nerve growth factor; EMSA, electromobility shift assay; SIF, sis-inducible factor; SIE, sis

  6. Metformin Induces Growth Inhibition and Cell Cycle Arrest by Upregulating MicroRNA34a in Renal Cancer Cells

    Science.gov (United States)

    Xie, Wei; Wang, Lei; Sheng, Halei; Qiu, Jing; Zhang, Di; Zhang, Le; Yang, Fan; Tang, Dahai; Zhang, Kebin

    2017-01-01

    Background Metformin is a widely used biguanide drug for the treatment of type 2 diabetes. It has been revaluated as a potential anti-cancer drug with promising activity in various tumors. However, the precise mechanisms underlying the suppression of cancer cells by metformin remain not well understood. Material/Methods In this study, human renal cell carcinoma cell line ACHN was used to investigate the anti-proliferation effect of metformin. A cell counting kit-8 assay was used to detect the cell viability. The cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of cyclin D1 and p27KIP1 was detected by Western blot. The underlying mechanism involving miRNA34a was further investigated by quantitative RT-PCR and transfection with miRNA inhibitor specific for miRNA34a in ACHN, 769-P, and A498 cells. Results Metformin could significantly inhibit the proliferation of ACHN cells in a dose- and time-dependent manner. In addition, the results showed that metformin induced G0/G1 phase arrest and delayed entry into S phase in ACHN cells. It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level. Furthermore, metformin increased ACHN cell death. Lastly, miRNA34a was found to be upregulated by metformin in ACHN, 769-P, and A498 cells. Subsequently, it was demonstrated that inhibition of miRNA34a could partially attenuate the suppressive effect of metformin on renal cancer cell proliferation. Conclusions The study data revealed that metformin induced cell growth inhibition and cell cycle arrest partially by upregulating miRNA34a in renal cancer cells. PMID:28045889

  7. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide

    Science.gov (United States)

    Ouyang, Gao-Liang; Cai, Qiu-Feng; Liu, Min; Chen, Rui-Chuan; Huang, Zhi; Jiang, Rui-Sheng; Chen, Fu; Hong, Shui-Gen; Bao, Shi-Deng

    2004-01-01

    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer. METHODS: Effects of HMBA on the growth of human hepatocellular carcinoma SMMC-7721 cells were assayed by MTT chronometry. Apoptosis induced by HMBA was detected by phase-contrast microscopy, flow cytometry, propidium iodide staining and immunocytochemical analysis. RESULTS: The growth of SMMC-7721 cells was significantly inhibited by HMBA, and the growth inhibitory rate was 51.1%, 62.6%, 68.7% and 73.9% respectively after treatment with 5.0, 7.5, 10.0 and 12.5 mmol/L of HMBA. In the cells treated with 10 mmol/L of HMBA for 72 h, the population of cells at sub-G1 phase significantly increased, and the apoptotic bodies and condensed nuclei were detected. Moreover, treatment of SMMC-7721 cells with 10 mmol/L of HMBA down-regulated the expression of Bcl-2 anti-apoptotic protein, while slightly up-regulated the level of pro-apoptotic protein Bax. CONCLUSION: Treatment with 10.0 mmol/L of HMBA can significantly inhibit the growth and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells by decreasing the ratio of Bcl-2 to Bax. PMID:15052673

  8. Arrest of myelination and reduced axon growth when Schwann cells lack mTOR.

    Science.gov (United States)

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J

    2012-02-01

    In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years, there has been an increased understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination, together with a growing appreciation of some of the signaling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete. The mammalian target of rapamycin (mTOR) is a core kinase in two major complexes, mTORC1 and mTORC2, that regulate cell growth and differentiation in a variety of mammalian cells. Here we show that elimination of mTOR from murine Schwann cells prevented neither radial sorting nor the initiation of myelination. However, normal postnatal growth of myelinating Schwann cells, both radially and longitudinally, was highly retarded. The myelin sheath in the mutant was much thinner than normal; nevertheless, sheath thickness relative to axon diameter (g-ratio) remained constant in both wild-type and mutant nerves from P14 to P90. Although axon diameters were normal in the mutant at the initiation of myelination, further growth as myelination proceeded was retarded, and this was associated with reduced phosphorylation of neurofilaments. Consistent with thinner axonal diameters and internodal lengths, conduction velocities in mutant quadriceps nerves were also reduced. These data establish a critical role for mTOR signaling in both the longitudinal and radial growth of the myelinating Schwann cell.

  9. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide

    Institute of Scientific and Technical Information of China (English)

    Gao-Liang Ouyang; Qiu-Feng Cai; Min Liu; Rui-Chuan Chen; Zhi Huang; Rui-Sheng Jiang; Fu Chen; Shui-Gen Hong; Shi-Deng Bao

    2004-01-01

    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer.METHODS: Effects of HMBA on the growth of human hepatocellular carcinoma SMMC-7721 cells were assayed by MTT chronometry. Apoptosis induced by HMBA was detected by phase-contrast microscopy, flow cytometry,propidium iodide staining and immunocytochemical analysis.RESULTS: The growth of SMMC-7721 cells was significantly inhibited by HMBA, and the growth inhibitory rate was 51.1%, 62.6%, 68.7% and 73.9% respectively after treatment with 5.0, 7.5, 10.0 and 12.5 mmol/L of HMBA.In the cells treated with 10 mmol/L of HMBA for 72 h, the population of cells at sub-G1 phase significantly increased,and the apoptotic bodies and condensed nuclei were detected. Moreover, treatment of SMMC-7721 cells with 10 mmol/L of HMBA down-regulated the expression of Bcl2 anti-apoptotic protein, while slightly up-regulated the level of pro-apoptotic protein Bax.CONCLUSION: Treatment with 10.0 mmol/L of HMBA can significantly inhibit the growth and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells by decreasing the ratio of Bcl-2 to Bax.

  10. H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anne-France Petit-Bertron

    Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

  11. Metformin inhibits salivary adenocarcinoma growth through cell cycle arrest and apoptosis

    OpenAIRE

    2015-01-01

    The inhibitory effects of metformin have been observed in many types of cancer. However, its effect on human salivary gland carcinoma is unknown. The effect of metformin alone or in combination with pp242 (an mTOR inhibitor) on salivary adenocarcinoma cells growth were determined in vitro and in vivo. We found that metformin suppressed HSY cell growth in vitro in a time and dose dependent manner associated with a reduced expression of MYC onco-protein, and the same inhibitory effect of metfor...

  12. Higher order nuclear organization in growth arrest of humanmammary epithelial cells: A novel role for telomere-associated proteinTIN2

    Energy Technology Data Exchange (ETDEWEB)

    Kaminker, Patrick; Plachot, Cedric; Kim, Sahn-Ho; Chung, Peter; Crippen, Danielle; Petersen, Ole W.; Bissell, Mina J.; Campisi, Judith; Lelievre, Sophie A.

    2004-12-15

    Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those which occur during differentiation and growth arrest. Using human mammary epithelial cells (HMECs) in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNAse, but not RNAse, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein l{gamma}. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in HMECs. Our findings reveal a novel extra-telomeric organization of TIN2 associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.

  13. Hinokitiol inhibits cell growth through induction of S-phase arrest and apoptosis in human colon cancer cells and suppresses tumor growth in a mouse xenograft experiment.

    Science.gov (United States)

    Lee, Youn-Sun; Choi, Kyeong-Mi; Kim, Wonkyun; Jeon, Young-Soo; Lee, Yong-Moon; Hong, Jin-Tae; Yun, Yeo-Pyo; Yoo, Hwan-Soo

    2013-12-27

    Hinokitiol (1), a tropolone-related natural compound, induces apoptosis and has anti-inflammatory, antioxidant, and antitumor activities. In this study, the inhibitory effects of 1 were investigated on human colon cancer cell growth and tumor formation of xenograft mice. HCT-116 and SW-620 cells derived from human colon cancers were found to be similarly susceptible to 1, with IC50 values of 4.5 and 4.4 μM, respectively. Compound 1 induced S-phase arrest in the cell cycle progression and decreased the expression levels of cyclin A, cyclin E, and Cdk2. Conversely, 1 increased the expression of p21, a Cdk inhibitor. Compound 1 decreased Bcl-2 expression and increased the expression of Bax, and cleaved caspase-9 and -3. The effect of 1 on tumor formation when administered orally was evaluated in male BALB/c-nude mice implanted intradermally separately with HCT-116 and SW-620 cells. Tumor volumes and tumor weights in the mice treated with 1 (100 mg/kg) were decreased in both cases. These results suggest that the suppression of tumor formation by compound 1 in human colon cancer may occur through cell cycle arrest and apoptosis.

  14. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masatoshi, E-mail: msuzuki@nagasaki-u.ac.jp [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan); Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

    2012-06-01

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO{sub 2}-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ss-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  15. Compensatory growth of Malaysian prawns reared at high densities during the nursery phase Crescimento compensatório em camarões-da-malásia cultivados sob altas densidades durante a fase de berçário

    Directory of Open Access Journals (Sweden)

    H.L.A. Marques

    2011-04-01

    Full Text Available The objective of this work was to verify the occurrence of compensatory growth in Malaysian prawn (Macrobrachium rosenbergii reared in pens, after being stocked in cages under high densities during nursery phase. The experiment was carried out in 0.5 m² cages and 2-m² pens set in natural bottom pond with 2,400 m². Prawn post-larvae (PL with an average weight of 0.026 ± 0.012 g (nursery phase were initially stocked in 16 cages at the densities of 50, 400, 800 and 1,200 PL m-2. Sixty days later, prawns were transferred to 16 growing pens, at the density of 12 prawns m-2. Initial average weight of the prawn in this phase was the final average weight registered in the nursery phase, as follows: 50 PL m-2 = 2.3 ± 0.3 g; 400 PL m-2 = 0.5 ± 0.03 g; 800 PL m-2 = 0.3 ± 0.05 g and 1,200 PL m-2 = 0.1 ± 0.01 g. Commercial rations for prawns (35% crude protein were given once a day, in the afternoon. After 244 days, survival, average weight and biomass did not differ significantly among prawns with different initial average weight. Relative growth rate was significantly greater in prawns previously stocked at 1,200 PL m-2 and feed conversion efficiency was significantly better for those previously stocked at 400 and 1,200 PL m-2. These results suggest the existence of partial compensatory growth in M. rosenbergii, what can successfully carry on stocking of prawns of this species at high densities in the nursery phase.Este trabalho foi realizado com o objetivo de verificar a ocorrência de crescimento compensatório em camarões-da-malásia (Macrobrachium rosenbergii cultivados em cercados, após serem estocados em gaiolas sob altas densidades durante a fase de berçário. O experimento foi conduzido em gaiolas com 0,5 m² e cercados com 2 m² instalados em um viveiro de fundo natural com 2.400 m². Pós-larvas (PL de camarões com peso médio de 0,026 ± 0,012 g (fase de berçário foram inicialmente estocadas em 16 gaiolas, nas densidades de 50, 400

  16. Obesity and high-density lipoprotein cholesterol in black and white 9- and 10-year-old girls : The National Heart, Lung, and Blood Institute Growth and Health Study

    NARCIS (Netherlands)

    Morrison, JA; Sprecher, D; McMahon, RP; Schreiber, GB; Khoury, PR

    1996-01-01

    It has been hypothesized that the role of obesity in the pathogenesis of coronary heart disease (CHD) may be mediated in part through its inverse relationship with high-density lipoprotein cholesterol (HDL-C). Obesity is inversely correlated with HDL-C, and HDL-C has been shown to be protective agai

  17. Obesity and high-density lipoprotein cholesterol in black and white 9- and 10-year-old girls : The National Heart, Lung, and Blood Institute Growth and Health Study

    NARCIS (Netherlands)

    Morrison, JA; Sprecher, D; McMahon, RP; Schreiber, GB; Khoury, PR

    1996-01-01

    It has been hypothesized that the role of obesity in the pathogenesis of coronary heart disease (CHD) may be mediated in part through its inverse relationship with high-density lipoprotein cholesterol (HDL-C). Obesity is inversely correlated with HDL-C, and HDL-C has been shown to be protective agai

  18. Arrest of Myelination and Reduced Axon Growth when Schwann Cells Lack mTOR

    OpenAIRE

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J.

    2012-01-01

    In developing peripheral nerves differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years there has been an increasing understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination together with a growing appreciation of some of the signalling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete....

  19. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest.

    Science.gov (United States)

    Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Fortner, Karen A; Viapiano, Mariano S; Jaworski, Diane M

    2015-08-01

    Glioblastoma (GBM), the most common primary adult malignant brain tumor, is associated with a poor prognosis due, in part, to tumor recurrence mediated by chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs exhibiting greater glycolytic metabolism and global hypoacetylation. However, little attention has been focused on the potential use of acetate supplementation as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis, are significantly reduced in GBM tumors. We recently demonstrated that NAA supplementation is not an appropriate therapeutic approach since it increases GSC proliferation and pursued an alternative acetate source. The FDA approved food additive Triacetin (glyceryl triacetate, GTA) has been safely used for acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA mutation. This study characterized the effects of GTA on the proliferation and differentiation of six primary GBM-derived GSCs relative to established U87 and U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural stem cells. GTA reduced proliferation of GSCs greater than established GBM lines. Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC growth, it also reduced cell viability. GTA-mediated growth inhibition was not associated with differentiation, but increased protein acetylation. These data suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy to inhibit GSC growth.

  20. Solanum tuberosum lectin inhibits Ehrlich ascites carcinoma cells growth by inducing apoptosis and G2/M cell cycle arrest.

    Science.gov (United States)

    Kabir, Syed Rashel; Rahman, Md Musfikur; Amin, Ruhul; Karim, Md Rezaul; Mahmud, Zahid Hayat; Hossain, M Tofazzal

    2016-06-01

    Recently, a lectin was purified from the potato cultivated in Bangladesh locally known as Sheel. In the present study cytotoxicity of the lectin against Ehrlich ascites carcinoma (EAC) cells was studied by MTT assay in vitro in RPMI-1640 medium and 8.0-36.0 % cell growth inhibition was observed at the range of 2.5-160 μg/ml protein concentration when incubated for 24 h. The lectin-induced apoptosis in EAC cells was confirmed by fluorescence and optical microscope. The apoptotic cell death was also confirmed by using caspase inhibitors. Cells growth inhibition caused by the lectin (36 %) was remarkably decreased to 7.6 and 22.3 % respectively in the presence of caspase-3 and -8 inhibitors. RT-PCR was used to evaluate the expression of apoptosis-related genes Bcl-X, p53, and Bax. An intensive expression of Bcl-X gene was observed in untreated control EAC cells with the disappeared of the gene in Sheel-treated EAC cells. At the same time, Bax gene expression appeared only in Sheel-treated EAC cells and the expression level of the p53 gene was increased remarkable after the treatment of EAC cells with the lectin. The lectin showed strong agglutination activity against EAC cells. Flow cytometry was used to study the cell cycle phases of EAC cells and it was observed that the lectin arrested the G2/M phase. In conclusion, Sheel lectin inhibited EAC cells growth by inducing apoptosis.

  1. High density semiconductor nanodots by direct laser fabrication

    Science.gov (United States)

    Haghizadeh, Anahita; Yang, Haeyeon

    2016-03-01

    We report a direct method of fabricating high density nanodots on the GaAs(001) surfaces using laser irradiations on the surface. Surface images indicate that the large clumps are not accompanied with the formation of nanodots even though its density is higher than the critical density above which detrimental large clumps begin to show up in the conventional Stranski-Krastanov growth technique. Atomic force microscopy is used to image the GaAs(001) surfaces that are irradiated by high power laser pulses interferentially. The analysis suggests that high density quantum dots be fabricated directly on semiconductor surfaces.

  2. Physeal growth arrest after tibial lengthening in achondroplasia: 23 children followed to skeletal maturity.

    Science.gov (United States)

    Song, Sang-Heon; Agashe, Mandar Vikas; Huh, Young-Jae; Hwang, Soon-Young; Song, Hae-Ryong

    2012-06-01

    Bilateral tibial lengthening has become one of the standard treatments for upper segment-lower segment disproportion and to improve quality of life in achondroplasia. We determined the effect of tibial lengthening on the tibial physis and compared tibial growth that occurred at the physis with that in non-operated patients with achondroplasia. We performed a retrospective analysis of serial radiographs until skeletal maturity in 23 achondroplasia patients who underwent bilateral tibial lengthening before skeletal maturity (lengthening group L) and 12 achondroplasia patients of similar height and age who did not undergo tibial lengthening (control group C). The mean amount of lengthening of tibia in group L was 9.2 cm (lengthening percentage: 60%) and the mean age at the time of lengthening was 8.2 years. The mean duration of follow-up was 9.8 years. Skeletal maturity (fusion of physis) occurred at 15.2 years in group L and at 16.0 years in group C. The actual length of tibia (without distraction) at skeletal maturity was 238 mm in group L and 277 mm in group C (p = 0.03). The mean growth rates showed a decrease in group L relative to group C from about 2 years after surgery. Physeal closure was most pronounced on the anterolateral proximal tibial physis, with relative preservation of the distal physis. Our findings indicate that physeal growth rate can be disturbed after tibial lengthening in achondroplasia, and a close watch should be kept for such an occurrence-especially when lengthening of more than 50% is attempted.

  3. Interleukin-1beta can mediate growth arrest and differentiation via the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells.

    Science.gov (United States)

    Park, Jong-In; Strock, Christopher J; Ball, Douglas W; Nelkin, Barry D

    2005-02-01

    Interleukin-1beta (IL-1beta) is a pleiotropic cytokine that can induce several cellular signal transduction pathways. Here, we show that IL-1beta can induce cell cycle arrest and differentiation in the human medullary thyroid carcinoma (MTC) cell line, TT. IL-1beta induces cell cycle arrest accompanied by morphological changes and expression of the neuroendocrine marker calcitonin. These changes are blocked by the MEK1/2 specific inhibitor U0126, indicating that MEK1/2 is essential for IL-1beta signaling in TT cells. IL-1beta induces expression of leukemia inhibitory factor (LIF) and activation of STAT3 via the MEK/ERK pathway. This activation of STAT3 could be abrogated by treatment with anti-LIF neutralizing antibody or anti-gp130 blocking antibody, indicating that induction of LIF expression is sufficient and essential for STAT3 activation by IL-1beta. In addition to activation of the LIF/JAK/STAT pathway, IL-1beta also induced an MEK/ERK-mediated intracellular cell-autonomous signaling pathway that is independently sufficient for growth arrest and differentiation. Thus, IL-1beta activates the MEK/ERK pathway to induce growth arrest and differentiation in MTC cells via dual independent signaling mechanisms, the cell-extrinsic LIF/JAK/STAT pathway, and the cell-intrinsic autonomous signaling pathway.

  4. Inhibitor of growth 4 suppresses colorectal cancer growth and invasion by inducing G1 arrest, inhibiting tumor angiogenesis and reversing epithelial-mesenchymal transition.

    Science.gov (United States)

    Qu, Hui; Yin, Hong; Yan, Su; Tao, Min; Xie, Yufeng; Chen, Weichang

    2016-05-01

    Previous studies have found that inhibitor of growth 4 (ING4), a tumor suppressor, is reduced in human colorectal cancer (CRC), and is inversely correlated with clinical Dukes' stage, histological grade, lymph node metastasis and microvessel density (MVD). However, its underlying mechanism remains undetermined. In the present study, we analyzed ING4 expression in a panel of human CRC cells using low (LS174T and SW480) and high (LoVo and SW620) metastatic cell lines. We demonstrated that both the low and high metastatic CRC cells exhibited a lower level of ING4 compared to the level in normal human colorectal mucous epithelial FHC cells. Furthermore, ING4 expression in high metastatic CRC cells was less than that in low metastatic CRC cells. We then generated a lentivirus construct expressing ING4 and green fluorescent protein (GFP), established a ING4-stably transgenic LoVo CRC cell line, and investigated the effect of lentiviral-mediated ING4 expression on high metastatic LoVo CRC cells. Gain-of-function studies revealed that ING4 significantly inhibited LoVo CRC cell growth and invasion in vitro and induced cell cycle G1 phase arrest. Moreover, ING4 obviously suppressed LoVo CRC subcutaneously xenografted tumor growth and reduced tumor MVD in vivo in athymic BALB/c nude mice. Mechanistically, ING4 markedly upregulated P21 and E-cadherin but downregulated cyclin E, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), Snail1, N-cadherin and vimentin in the LoVo CRC cells. Our data provide compelling evidence that i) ING4 suppresses CRC growth possibly via induction of G1 phase arrest through upregulation of P21 cyclin-dependent kinase (CDK) inhibitor and downregulation of cyclin E as well as inhibition of tumor angiogenesis through reduction of IL-6, IL-8 and VEGF proangiogenic factors; ii) ING4 inhibits CRC invasion and metastasis probably via a switch from mesenchymal marker N-cadherin to epithelial marker E-cadherin through downregulation of

  5. Linear Growth Arrest Without Weight Gain Due to Overuse of Topical Clobetasol

    Directory of Open Access Journals (Sweden)

    Zahra Razavi

    2014-11-01

    Full Text Available Prolonged potent topical glucocorticoid therapy in infants can cause iatrogenic Cushing’s syndrome. This case highlights the rarity of poor weight gain in iatrogenic Cushing’s syndrome. A 17-month-old boy was referred to outpatients pediatric endocrine clinic for evaluation of growth failure. On presentation his weight was 9.7kg (5th percentile and height was 72cm (-3.6 SD below mean for age and sex. Systemic examination revealed grossly moon-like face, hypertrichosis and thin skin in the genital area. His mother reported using local clobetasol for the previous seven months for his diaper dermatitis. Baseline plasma cortisol was low (0.3ng/ml, normal range: 60 to 280ng/ml. During standard dose of synthetic adrenocorticotropic hormone test, the peak cortisol level was 0.4ng/ml (N>180ng/ml and was consistent with hypothalamic–pituitary–adrenal axis suppression. The patient’s clinical presentation and laboratory investigations confirmed the diagnosis of secondary adrenal insufficiency and iatrogenic Cushing’s syndrome. He was treated successfully by discontinuing use of clobetasol. His appearance and growth returned to normal within two months. Morning cortisol was 101.2ng/ml after stopping the oral physiologic dose of hydrocortisone. Our case differed from other reports of iatrogenic Cushing’s syndrome by presenting in poor weight gain rather than obesity.

  6. Growth arrest of vascular smooth muscle cells in suspension culture using low-acyl gellan gum.

    Science.gov (United States)

    Natori, Tomomi; Fujiyoshi, Masachika; Uchida, Masashi; Abe, Natsuki; Kanaki, Tatsuro; Fukumoto, Yasunori; Ishii, Itsuko

    2017-03-01

    The proliferation of vascular smooth muscle cells (SMCs) causes restenosis in biomaterial vascular grafts. The purposes of this study were to establish a suspension culture system for SMCs by using a novel substrate, low-acyl gellan gum (GG) and to maintain SMCs in a state of growth inhibition. When SMCs were cultured in suspension with GG, their proliferation was inhibited. Their viability was 70% at day 2, which was maintained at more than 50% until day 5. In contrast, the viability of cells cultured in suspension without GG was 5.6% at day 2. By cell cycle analysis, the ratio of SMCs in the S phase when cultured in suspension with GG was lower than when cultured on plastic plates. In SMCs cultured in suspension with GG, the ratio of phosphorylated retinoblastoma (Rb) protein to Rb protein was decreased and p27(Kip1) expression was unchanged in comparison with SMCs cultured on plastic plates. In addition, SMCs could be induced to proliferate again by changing the culture condition from suspension with GG to plastic plates. These results suggest that our established culturing method for SMCs is useful to maintain SMCs in a state of growth inhibition with high viability.

  7. Growth arrest of BCR-ABL positive cells with a sequence-specific polyamide-chlorambucil conjugate.

    Directory of Open Access Journals (Sweden)

    C James Chou

    Full Text Available Chronic myeloid leukemia (CML is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model.

  8. Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate

    Science.gov (United States)

    Chou, C. James; O'Hare, Thomas; Lefebvre, Sophie; Alvarez, David; Tyner, Jeffrey W.; Eide, Christopher A.; Druker, Brian J.; Gottesfeld, Joel M.

    2008-01-01

    Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model. PMID:18974832

  9. Silica Nanoparticles Sensitize Human Multiple Myeloma Cells to Snake (Walterinnesia aegyptia Venom-Induced Apoptosis and Growth Arrest

    Directory of Open Access Journals (Sweden)

    Douaa Sayed

    2012-01-01

    Full Text Available Background. Multiple myeloma (MM, an almost incurable disease, is the second most common blood cancer. Initial chemotherapeutic treatment could be successful; however, resistance development urges the use of higher toxic doses accompanied by hematopoietic stem cell transplantation. The establishment of more effective treatments that can overcome or circumvent chemoresistance has become a priority. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV either alone or in combination with silica nanoparticles (WEV+NPs mediated the growth arrest and apoptosis of prostate cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on proliferation and apoptosis of MM cells. Methods. The impacts of WEV alone and WEV+NP were monitored in MM cells from 70 diagnosed patients. The influences of WEV and WEV+NP were assessed with flow cytometry analysis. Results. WEV alone and WEV+NP decreased the viability of MM cells. Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited MM cell proliferation. Furthermore, analysis of the cell cycle using the propidium iodide (PI staining method indicated that WEV+NP strongly altered the cell cycle of MM cells and enhanced the induction of apoptosis. Conclusions. Our data reveal the biological effects of WEV and WEV+NP on MM cells that enable these compounds to function as effective treatments for MM.

  10. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    Full Text Available Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1 as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  11. Overexpression of the promyelocytic leukemia gene suppresses growth of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis

    Institute of Scientific and Technical Information of China (English)

    HE Dalin 贺大林; NAN Xunyi 南勋义; Chang Kun-Song; WANG Yafeng 王亚峰; Chung Leland W.K.

    2003-01-01

    Objectives To examine the anti-oncogenic effects of promyelocytic leukemia (PML) on bladder cancer and to explore its molecular mechanisms of growth suppression.Methods Wild-type PML was transfected into bladder cancer cells (5637 cell) and expressed in a replication-deficient adenovirus-mediated gene delivery system and introduced into human bladder cancer cells (5637 cell) in vitro and in vivo. The effect and mechanisms of the PML gene in cell growth, clonogenicity, and tumorigenicity of bladder cancer cells were studied using in vitro and in vivo growth assays, soft agar colony-forming assay, cell cycle analysis, apoptosis assay and in vivo tumorigenicity assay.Results Overexpression of PML in 5637 cells significantly reduced their growth rate and clonogenicity on soft agar. PML suppressed bladder cancer cell growth by inducing G1 cell cycle arrest and apoptosis. Adenovirus-mediated PML (Ad-PML) significantly suppressed the tumorigenicity and growth of bladder cancer cells. Intratumoral injection of Ad-PML into tumors induced by 5637 cells dramatically suppressed their growth. Conclusions The results indicated that overexpression of PML protein may promote efficient growth inhibition of human bladder cancer cells by inducing G1 cell cycle arrest and apoptosis, and adenovirus-mediated PML (Ad-PML) expression efficiently suppresses human bladder cancer growth.

  12. Antisense oligonucleotide targeting at the initiator of hTERT arrests growth of hepatoma cells

    Science.gov (United States)

    Liu, Su-Xia; Sun, Wen-Sheng; Cao, Ying-Lin; Ma, Chun-Hong; Han, Li-Hui; Zhang, Li-Ning; Wang, Zhen-Guang; Zhu, Fa-Liang

    2004-01-01

    AIM: To evaluate the inhibitory effect of antisense phosphorothioate oligonucleotide (asON) complementary to the initiator of human telomerase catalytic subunit (hTERT) on the growth of hepatoma cells. METHODS: The as-hTERT was synthesized by using a DNA synthesizer. HepG2.2.15 cells were treated with as-hTERT at the concentration of 10 μmol/L. After 72 h, these cells were obtained for detecting growth inhibition, telomerase activity using the methods of MTT, TRAP-PCR-ELISA, respectively. BALB/c(nu/nu) mice were injected HepG2.2.15 cells and a human-nude mice model was obtained. There were three groups for anti-tumor activity study. Once tumors were established, these animals in the first group were administered as-hTERT and saline. Apoptosis of tumor cells was detected by FCM. In the 2nd group, the animals were injected HepG2.2.15 cells together with as-hTERT. In the third group, the animals were given as-hTERT 24 hours postinjection of HepG2.2.15 cells. The anti-HBV effects were assayed with ELISA in vitro and in vivo. RESULTS: Growth inhibition was observed in cells treated with as-hTERT in vitro. A significant different in the value of A570 - A630 was found between cells treated with as-hTERT and control (P < 0.01) by MTT method. The telomerase activity of tumor cells treated with as-hTERT was reduced, the value of A450 nm was 0.42 compared to control (1.49) with TRAP-PCR-ELISA. The peak of apoptosis in tumor cells given as-hTERT was 21.12%, but not seen in saline-treated control. A prolonged period of carcinogenesis was observed in the second and third group animals. There was inhibitory effect on the expression of HBsAg and HBeAg in vivo and in vitro. CONCLUSION: As-hTERT has an anti-tumor activity, which may be useful for gene therapy of tumors. PMID:14760759

  13. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Bai-He Liu; Yao Li; Fang Liu; Jian Guo; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of growth inhibition ofhuman gastric cancer SGC-7901 cell with RRR-α-tocopherylsuccinate (VES), a derivative of natural Vitamin E, viainducing apoptosis and DNA synthesis arrest.METHODS: Human gastric cancer SGC-7901 cells wereregularly incubated in the presence of VES at 5, 10 and20mg@ L 1(VES was dissolved in absolute ethanol anddiluted in RPMI 1640 complete condition mediacorrespondingly to a final concentration of VES and 1mL@L-1 ethanol), succinic acid and ethanol equivalents asvehicle (VEH) control andcondition media only asuntreated (UT) control. Trypan blue dye exclusionanalysis and MTT assay were applied to detect the cellproliferation. 37kBq of tritiated thymidine was added tocells and [3H] TdR uptake was measured to observe DNAsynthesis. Apoptotic morphology was observed byelectron microscopy and DAPI staining. Flow cytometryand terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling (TUNEL) assay were performed to detectVES-triggered apoptosis.RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppressionby 24.7%, 49.2% and 68.7% following 24h of VEStreatment at 5, 10 and 20 mg@L 1, respectively, similar tothe findings from MTT assay. DNA synthesis wasevidently reduced by 35%, 45% and 98% after 24h VEStreatment at 20 mg@ L-1 and 48h at 10 and 20 mg@ L 1,respectively. VES induced SGC-7901 cells to undergoapoptosis with typically apoptotic characteristics,including morphological changes of chromatincondensation, chromatin crescent formation/margination,nucleus fragmentation and apoptotic body formation,typical apoptotic sub-G1 peak by flow cytometry andincrease of apoptotic cells by TUNEL assay in which 90%of cells underwent apoptosis after 48h of VES treatment at20 mcg@L-1.CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesisarrest. Inhibition of SGC-7901 cell growth by VES is dose-and time

  14. Aureobasidin A arrests growth of yeast cells through both ceramide intoxication and deprivation of essential inositolphosphorylceramides

    DEFF Research Database (Denmark)

    Cerantola, Vanessa; Guillas, Isabelle; Roubaty, Carole

    2009-01-01

    , 2Delta.YDC1 cells stop growing when exposed to Aureobasidin A (AbA), an inhibitor of the inositolphosphorylceramide synthase AUR1, yet their ceramide levels remain very low. This finding argues against a current hypothesis saying that yeast cells do not require inositolphosphorylceramides and die...... in the presence of AbA only because ceramides build up to toxic concentrations. Moreover, W303lag1Delta lac1Delta ypc1Delta ydc1Delta cells, reported to be AbA resistant, stop growing on AbA after a certain number of cell divisions, most likely because AbA blocks the biosynthesis of anomalous...... inositolphosphorylsphingosides. Thus, data argue that inositolphosphorylceramides of yeast, the equivalent of mammalian sphingomyelins, are essential for growth. Data also clearly confirm that wild-type strains, when exposed to AbA, immediately stop growing because of ceramide intoxication, long before...

  15. Growth Arrest Line Mimicking Lymphoma Involvement: The Findings of (99m)Tc-MDP Bone SPECT/CT and Serial Bone Scan in a Child with Non-Hodgkin's Lymphoma.

    Science.gov (United States)

    Kim, Chanwoo; Kim, Ji Young; Choi, Yun Young; Lee, Seunghun; Lee, Young-Ho

    2016-06-01

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on (99m)Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.

  16. Growth arrest line mimicking lymphoma involvement: The findings of {sup 99m}Tc-MDP bone SPECT/CT and serial bone scan in a child with non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chan Woo; Kim, Ji Young; Choi, Yun Young; Lee, Seung Hun; Lee, Young Ho [Hanyang University Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on {sup 99m}Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.

  17. Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis.

    Science.gov (United States)

    Chatterjee, Nirupama; Anwar, Tarique; Islam, Nashreen S; Ramasarma, T; Ramakrishna, Gayatri

    2016-09-01

    Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in GTPase activity of Rac1, accumulation of the reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV-mediated growth arrest was significantly abrogated in cells pre-treated with the N-acetylcysteine, Rac1 knocked down by siRNA and DPI an inhibitor of NADPH oxidase. In conclusion, our results show that polyacrylate derivative of peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1-NADPH oxidase leading to oxidative stress and DNA damage.

  18. Arecoline-induced growth arrest and p21WAF1 expression are dependent on p53 in rat hepatocytes.

    Science.gov (United States)

    Chou, Wen-Wen; Guh, Jinn-Yuh; Tsai, Jung-Fa; Hwang, Chi-Ching; Chen, Hung-Chun; Huang, Jau-Shyang; Yang, Yu-Lin; Hung, Wen-Chun; Chuang, Lea-Yea

    2008-01-14

    Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma and arecoline, the major alkaloid of betel-quid, is hepatotoxic in mice. Therefore, we studied the cytotoxic and genotoxic effects of arecoline in normal rat hepatocytes (Clone-9 cells). Arecoline dose-dependently (0.1-1mM) decreased cell cycle-dependent proliferation while inducing DNA damage at 24h. Moreover, arecoline (1mM)-induced apoptosis and necrosis at 24h. Arecoline dose-dependently (0.1-0.5mM) increased transforming growth factor-beta (TGF-beta) mRNA, gene transcription and bioactivity and neutralizing TGF-beta antibody attenuated arecoline (0.5mM)-inhibited cell proliferation at 24h. Arecoline (0.5mM) also increased p21(WAF1) protein expression and p21(WAF1) gene transcription. Moreover, arecoline (0.5mM) time-dependently (8-24h) increased p53 serine 15 phosphorylation. Pifithrin-alpha (p53 inhibitor) and the loss of the two p53-binding elements in the p21(WAF1) gene promoter attenuated arecoline-induced p21(WAF1) gene transcription at 24h. Pifithrin-alpha also attenuated arecoline (0.5mM)-inhibited cell proliferation at 24h. We concluded that arecoline induces cytotoxicity, DNA damage, G(0)/G(1) cell cycle arrest, TGF-beta1, p21(WAF1) and activates p53 in Clone-9 cells. Moreover, arecoline-induced p21(WAF1) is dependent on p53 while arecoline-inhibited growth is dependent on both TGF-beta and p53.

  19. Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis.

    Science.gov (United States)

    Qi, Runzi; An, Huazhang; Yu, Yizhi; Zhang, Minghui; Liu, Shuxun; Xu, Hongmei; Guo, Zhenghong; Cheng, Tao; Cao, Xuetao

    2003-12-01

    Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation, and apoptosis; hence, perturbed Notch signaling may contribute to tumorigenesis. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in Africa and Asia. The mechanisms that orchestrate the multiple oncogenic insults required for initiation and progression of HCC are not clear. We constitutively overexpressed active Notch1 in human HCC to explore the effects of Notch1 signaling on HCC cell growth and to investigate the underlying molecular mechanisms. We show here that overexpression of Notch1 was able to inhibit the growth of HCC cells in vitro and in vivo. Biochemical analysis revealed the involvement of cell cycle regulated proteins in Notch1-mediated G(0)/G(1) arrest of HCC cells. Compared with green fluorescent protein (GFP) control, transient transfection of Notch1 ICN decreased expression of cyclin A (3.5-fold), cyclin D1 (2-fold), cyclin E (4.5-fold), CDK2 (2.8-fold), and the phosphorylated form of retinoblastoma protein (3-fold). Up-regulation of p21(waf/cip1) protein expression was observed in SMMC7721-ICN cells stably expressing active Notch1 but not in SMMC7721-GFP cells, which only express GFP. Furthermore, a 12-fold increase in p53 expression and an increase (4.8-fold) in Jun-NH(2)-terminal kinase activation were induced in SMMC7721-ICN cells compared with SMMC7721-GFP cells. In contrast, expression of the antiapoptotic Bcl-2 protein could not be detected in SMMC7721-ICN cells. These findings suggest that Notch1 signaling may participate in the development of HCC cells, affecting multiple pathways that control both cell proliferation and apoptosis.

  20. Serum Growth Arrest Specific Protein 6 (Gas-6 Levels in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Fethullah Gerin

    2016-03-01

    Full Text Available Objective: We have investigated serum growth ar­rest-specific protein 6 (GAS-6 levels from patients with schizophrenia divided into acute phase remission phases as well as control group. Methods: This study was conducted in Psychiatry De­partment of Istanbul University Cerrahpasa Medical Fac­ulty. The patients who were diagnosed with schizophrenia after regular psychiatric examination according to DSM-IV criteria (n=22 as well as control subjects were includ­ed in the study. Schizophrenia patients with acute phase and remission phase were evaluated by Positive and Negative Syndrome Scale (PANSS and Clinical global Impression Scale (CGI-S. The serum GAS-6 levels of schizophrenia patients during acute phase and remission phase were compared with the serum GAS-6 levels of healthy controls. Serum GAS-6 levels were measured by commercial ELISA kits. Results: No difference was found in serum GAS-6 levels among the three groups; schizophrenia with acute phase, schizophrenia with remission phase, and controls. There were no correlations between serum GAS-6 levels and PANSS and CGI scores. Conclusion: To reach a definitive data and better in­terpretation about the relationship between GAS-6 and schizophrenia, future studies with larger groups of pa­tients with schizophrenia subdivided by drug naïve and treated with antipsychotics/other treatment modalities and controls are needed.

  1. Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901

    Institute of Scientific and Technical Information of China (English)

    王宽; 张岂凡; 王锡山; 薛英威; 庞达; 傅松滨

    2004-01-01

    Background Peptide nucleic acid (PNA) has many characteristics useful in molecular biology. This paper described an effective way to raise the cell ingestion rate of PNA so as to kill gastric cancer cells.Methods Heteroduplexes of PNAs and oligonucleotides, wrapped by Lipofectamine 2000, were used to infect SGC7901 cells. The inhibitive effect of heteroduplexes was evaluated by analyzing cell clone forming and cell growth rate. Telomerase activity of SGC7901 cells was detected by polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) and silver staining assay.Results PNAs showed a dose-dependent inhibition of cell proliferation. The percentage of proliferation inhibition was 99.4% after 7 days; the rate of cloning inhibition was 98.2% after 8 days;whereas for oligonucleotide groups, at the same concentration, the percentages were 50. 1% and 67. 5% respectively. Antisense PNA-DNA-Lipofectamine 2000 group (AP-D-L group) exhibited significantly different percentages from the control groups (P<0.05). The test result indicated that telomerase activity of the AP-D-L group was inhibited (P<0.05). At the same time, the impact on cell morphology was observed.Conclusions The results showed that PNAs are potent antisense reagents. The telomeraseassociated therapies are very promising for the treatment of malignant tumours.

  2. Growth arrest and rapid capture of select pathogens following magnetic nanoparticle treatment.

    Science.gov (United States)

    Niemirowicz, Katarzyna; Swiecicka, Izabela; Wilczewska, Agnieszka Z; Markiewicz, Karolina H; Surel, Urszula; Kułakowska, Alina; Namiot, Zbigniew; Szynaka, Beata; Bucki, Robert; Car, Halina

    2015-07-01

    Thorough understanding of magnetic nanoparticle (MNP) properties is essential for developing new theranostics. In this study, we provide evidence that non-modified magnetic iron oxide nanoparticles and their functionalized derivatives may be used to restrict growth and capture different pathogens. Coprecipitation of Fe(2+) and Fe(3+) ions in an alkaline solution was used to synthesize MNPs that subsequently were functionalized by gold and aminosilane coating. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were used to assess their physicochemical properties. A significant decrease of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans outgrown from medium after addition of MNPs or their derivatives was observed during 24h culture. Measurement of optical density revealed that using MNPs, these pathogens can be quickly captured and removed (with efficiency reaching almost 100%) from purposely infected saline buffer and body fluids such as human blood plasma, serum, abdominal fluids and cerebrospinal fluids. These effects depend on nanoparticle concentration, surface chemistry, the type of pathogen, as well as the surrounding environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol

    Science.gov (United States)

    SONER, BURAK CEM; AKTUG, HUSEYIN; ACIKGOZ, EDA; DUZAGAC, FAHRIYE; GUVEN, UMMU; AYLA, SULE; CAL, CAG; OKTEM, GULPERI

    2014-01-01

    Flavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity, apoptosis and G1-phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)+high/CD44+high prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose- and time-dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere-forming assay. Flavopiridol was applied to monolayer cultures of CD133high/CD44high human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM. The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC50) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin-V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G0/G1 analysis showed a statistically significant difference between 100 and 500 nM (P<0.005), 100 and 1000 nM (P<0.001), 300 and 1000 nM (P<0.001), and 500 and 1000 nM (P<0.001). Flavopiridol also significantly influenced the cells in the G2/M phase, particularly at high-dose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC50 dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase-3, caspase-8 and p53. In conclusion, the present results indicated that flavopiridol could be a

  4. Fertilización de base en un cultivo inicial de pecan con dos marcos de plantación de alta densidad Effect of different fertilization strategies on pecan growth parameters under two high density plantation frames

    Directory of Open Access Journals (Sweden)

    Lidia Giuffré

    2011-07-01

    pecan fertilization and planting systems. The objectives of this study were to characterize some physical-chemical and chemical properties in a pecan crop, and compare different basal fertilization (FB treatments under two high density plantation frames (MP. Plantation was conducted in Villanueva (Buenos Aires province, on a Tapthoargic Hapludoll, with 10 x 10 m frames (real part: MR and 8 x 8 m frames (staggered: TR. The experimental design was a split plot with four replications. The main plots were the two frames and the subplots were the different fertilization treatments: Compost (C, Phosphorus (P, slow release Nitrogen (N, and an unfertilized control (T. The determinations to assess the growth of pecan plants were: plant height and stem diameter. With regard to soil fertility, phosphorus fertilization and the addition of compost significatively increased the levels of Bray-P. The organic fertilizer treatment (compost showed a significant increase in the height of the pecan plantation under the 8 x 8 m frame, which was not apparent in any case for the stem diameter, with a MP x FB significant interaction (P = 0.01 for height variation in the first year. The plantation frame with or without basal fertilization had no effect on pecan volume during the study period.

  5. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Qinghe Chen

    Full Text Available BACKGROUND: Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Although resveratrol possesses chemopreventive properties against several cancers, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. The present study was carried out to examine whether PI3K/AKT/FOXO pathway mediates the biological effects of resveratrol. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors (LY294002 and Wortmannin and AKT inhibitor alone slightly induced apoptosis in LNCaP cells. These inhibitors further enhanced the apoptosis-inducing potential of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis. Wild type PTEN and PTEN-G129E enhanced resveratrol-induced apoptosis, whereas PTEN-G129R had no effect on proapoptotic effects of resveratrol. Furthermore, apoptosis-inducing potential of resveratrol was enhanced by dominant negative AKT, and inhibited by wild-type AKT and constitutively active AKT. Resveratrol has no effect on the expression of FKHR, FKHRL1 and AFX genes. The inhibition of FOXO phosphorylation by resveratrol resulted in its nuclear translocation, DNA binding and transcriptional activity. The inhibition of PI3K/AKT pathway induced FOXO transcriptional activity resulting in induction of Bim, TRAIL, p27/KIP1, DR4 and DR5, and inhibition of cyclin D1. Similarly, resveratrol-induced FOXO transcriptional activity was further enhanced when activation of PI3K/AKT pathway was blocked. Over-expression of phosphorylation deficient mutants of FOXO proteins (FOXO1-TM, FOXO3A-TM and FOXO4-TM induced FOXO transcriptional activity, which was further enhanced by resveratrol. Inhibition of FOXO transcription factors by shRNA blocked resveratrol-induced upregulation of Bim, TRAIL, DR4, DR5, p27/KIP1 and

  6. Daily Arrests

    Data.gov (United States)

    Montgomery County of Maryland — This dataset provides the public with arrest information from the Montgomery County Central Processing Unit (CPU) systems. The data presented is derived from every...

  7. The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis following low dose UVB radiation.

    Science.gov (United States)

    Liao, Yi; Feng, Jianguo; Zhang, Yi; Tang, Liling; Wu, Shiyong

    2017-06-01

    UV induces CIRP expression and subsequent Stat3 activation, but the biological function and mechanism of CIRP and Stat3 in mediating UVB-induced skin carcinogenesis have not been fully elucidated. In this study, we demonstrate that CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines; and the expression of CIRP is upregulated in keratinocytes after being irradiated with relatively low dose (dose (50 mJ/cm(2) ), UVB acutely and chronically. The increased expression of CIRP, either induced by UVB or through overexpression, leads to resistance of keratinocytes to UVB-induced growth arrest and death; and reduced expression of CIRP by RNA knockdown sensitizes keratinocyte cells to the low dose UVB radiation. We also demonstrated that CIRP expression is required for the low dose UVB-induced Tyr705-phosphorylation, but not total amount, of Stat3. The p-Stat3 level is correlated with the expression levels of cyclin D1 and VEGF, two known downstream cell growth regulators of Stat3, as well as Bag-1/S, an apoptosis regulator. Inhibition of Stat3 DNA-binding activity by S3I-201 leads to a reduction of the p-Stat3 and Bag-1/S along with growth and survival of keratinocytes post-UVB; and the effect of S3I-201 on the UVB-irradiated cells can be partially inhibited by overexpression of CIRP or Bag-1/S. Furthermore, the overexpression of Bag-1/S can totally inhibit UVB-induced PARP cleavage and caspase 3 activation. The results presented above led us to propose that CIRP-p(705)Stat3 cascade promotes cell proliferation and survival post-UVB via upregulating the expression of cyclin D1 and Bag-1/S, respectively. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  8. LKB1 Haploinsufficiency Cooperates With Kras to Promote Pancreatic Cancer Through Suppression of p21-Dependent Growth Arrest

    Science.gov (United States)

    Morton, Jennifer P.; Jamieson, Nigel B.; Karim, Saadia A.; Athineos, Dimitris; Ridgway, Rachel A.; Nixon, Colin; McKay, Colin J.; Carter, Ross; Brunton, Valerie G.; Frame, Margaret C.; Ashworth, Alan; Oien, Karin A.; Evans, T.R. Jeffry; Sansom, Owen J.

    2010-01-01

    Background & Aims Patients carrying germline mutations of LKB1 have an increased risk of pancreatic cancer; however, it is unclear whether down-regulation of LKB1 is an important event in sporadic pancreatic cancer. In this study, we aimed to investigate the impact of LKB1 down-regulation for pancreatic cancer in mouse and human and to elucidate the mechanism by which Lkb1 deregulation contributes to this disease. Methods We first investigated the consequences of Lkb1 deficiency in a genetically modified mouse model of pancreatic cancer, both in terms of disease progression and at the molecular level. To test the relevance of our findings to human pancreatic cancer, we investigated levels of LKB1 and its potential targets in human pancreatic cancer. Results We definitively show that Lkb1 haploinsufficiency can cooperate with oncogenic KrasG12D to cause pancreatic ductal adenocarcinoma (PDAC) in the mouse. Mechanistically, this was associated with decreased p53/p21-dependent growth arrest. Haploinsufficiency for p21 (Cdkn1a) also synergizes with KrasG12D to drive PDAC in the mouse. We also found that levels of LKB1 expression were decreased in around 20% of human PDAC and significantly correlated with low levels of p21 and a poor prognosis. Remarkably, all tumors that had low levels of LKB1 had low levels of p21, and these tumors did not express mutant p53. Conclusions We have identified a novel LKB1-p21 axis that suppresses PDAC following Kras mutation in vivo. Down-regulation of LKB1 may therefore serve as an alternative to p53 mutation to drive pancreatic cancer in vivo. PMID:20452353

  9. Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    Rui Zhao

    2016-01-01

    Full Text Available Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6, is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD. We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl−1 (P < 0.001 and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml−1 (P < 0.001 in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.

  10. Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification.

    Science.gov (United States)

    Son, Bo-Kyung; Akishita, Masahiro; Iijima, Katsuya; Ogawa, Sumito; Maemura, Koji; Yu, Jing; Takeyama, Kenichi; Kato, Shigeaki; Eto, Masato; Ouchi, Yasuyoshi

    2010-03-05

    Recent epidemiological studies have found that androgen deficiency is associated with a higher incidence of cardiovascular disease in men. However, little is known about the mechanism underlying the cardioprotective effects of androgens. Here we show the inhibitory effects of testosterone on vascular calcification and a critical role of androgen receptor (AR)-dependent transactivation of growth arrest-specific gene 6 (Gas6), a key regulator of inorganic phosphate (P(i))-induced calcification of vascular smooth muscle cells (VSMC). Testosterone and nonaromatizable androgen dihydrotestosterone inhibited P(i)-induced calcification of human aortic VSMC in a concentration-dependent manner. Androgen inhibited P(i)-induced VSMC apoptosis, an essential process for VSMC calcification. The effects on VSMC calcification were mediated by restoration of P(i)-induced down-regulation of Gas6 expression and a subsequent reduction of Akt phosphorylation. These effects of androgen were blocked by an AR antagonist, flutamide, but not by an estrogen receptor antagonist, ICI 182,780. We then explored the mechanistic role of the AR in Gas6 expression and found an abundant expression of AR predominantly in the nucleus of VSMC and two consensus ARE sequences in the Gas6 promoter region. Dihydrotestosterone stimulated Gas6 promoter activity, and this effect was abrogated by flutamide and by AR siRNA. Site-specific mutation revealed that the proximal ARE was essential for androgen-dependent transactivation of Gas6. Furthermore, chromatin immunoprecipitation assays demonstrated ligand-dependent binding of the AR to the proximal ARE of Gas6. These results indicate that AR signaling directly regulates Gas6 transcription, which leads to inhibition of vascular calcification, and provides a mechanistic insight into the cardioprotective action of androgens.

  11. Picropodophyllin causes mitotic arrest and catastrophe by depolymerizing microtubules via insulin-like growth factor-1 receptor-independent mechanism.

    Science.gov (United States)

    Waraky, Ahmed; Akopyan, Karen; Parrow, Vendela; Strömberg, Thomas; Axelson, Magnus; Abrahmsén, Lars; Lindqvist, Arne; Larsson, Olle; Aleem, Eiman

    2014-09-30

    Picropodophyllin (PPP) is an anticancer drug undergoing clinical development in NSCLC. PPP has been shown to suppress IGF-1R signaling and to induce a G2/M cell cycle phase arrest but the exact mechanisms remain to be elucidated. The present study identified an IGF-1-independent mechanism of PPP leading to pro-metaphase arrest. The mitotic block was induced in human cancer cell lines and in an A549 xenograft mouse but did not occur in normal hepatocytes/mouse tissues. Cell cycle arrest by PPP occurred in vitro and in vivo accompanied by prominent CDK1 activation, and was IGF-1R-independent since it occurred also in IGF-1R-depleted and null cells. The tumor cells were not arrested in G2/M but in mitosis. Centrosome separation was prevented during mitotic entry, resulting in a monopolar mitotic spindle with subsequent prometaphase-arrest, independent of Plk1/Aurora A or Eg5, and leading to cell features of mitotic catastrophe. PPP also increased soluble tubulin and decreased spindle-associated tubulin within minutes, indicating that it interfered with microtubule dynamics. These results provide a novel IGF-1R-independent mechanism of antitumor effects of PPP.

  12. High Density Metamaterials for Visible Light

    Science.gov (United States)

    2016-11-28

    Split Ring Resonator Metamaterials with Fundamental Magnetic Resonance in the Middle Visible Spectrum,” Adv. Opt. Mater., vol. 2, no. 3, pp. 280–285...AFRL-AFOSR-JP-TR-2016-0097 High density metamaterials for visible light Dao Hua Zhang NANYANG TECHNOLOGICAL UNIVERSITY Final Report 11/28/2016...COVERED (From - To)  16 Jul 2014 to 15 Jul 2016 4. TITLE AND SUBTITLE High density metamaterials for visible light 5a.  CONTRACT NUMBER 5b.  GRANT

  13. A class of DNA-binding peptides from wheat bud causes growth inhibition, G2 cell cycle arrest and apoptosis induction in HeLa cells

    Directory of Open Access Journals (Sweden)

    Elgjo Kjell

    2009-07-01

    Full Text Available Abstract Background Deproteinized DNA from eukaryotic and prokaryotic cells still contains a low-molecular weight peptidic fraction which can be dissociated by alkalinization of the medium. This fraction inhibits RNA transcription and tumor cell growth. Removal from DNA of normal cells causes amplification of DNA template activity. This effect is lower or absent in several cancer cell lines. Likewise, the amount of active peptides in cancer cell DNA extracts is lower than in DNA preparation of the corresponding normal cells. Such evidence, and their ubiquitous presence, suggests that they are a regulatory, conserved factor involved in the control of normal cell growth and gene expression. Results We report that peptides extracted from wheat bud chromatin induce growth inhibition, G2 arrest and caspase-dependent apoptosis in HeLa cells. The growth rate is decreased in cells treated during the S phase only and it is accompanied by DNA damage and DNA synthesis inhibition. In G2 cells, this treatment induces inactivation of the CDK1-cyclin B1 complex and an increase of active chk1 kinase expression. Conclusion The data indicate that the chromatin peptidic pool inhibits HeLa cell growth by causing defective DNA replication which, in turn, arrests cell cycle progression to mitosis via G2 checkpoint pathway activation.

  14. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Vucic V.

    2006-01-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  15. Regenerative Endodontic Treatment of an Immature Necrotic Molar with Arrested Root Development by Using Recombinant Human Platelet-derived Growth Factor: A Case Report.

    Science.gov (United States)

    Zhujiang, Annie; Kim, Sahng G

    2016-01-01

    Regenerative endodontic treatment has provided a treatment option that aims to allow root maturation. The present report describes the regenerative endodontic treatment of a necrotic, immature molar by using recombinant human platelet-derived growth factor (rhPDGF-BB) and shows the continued root maturation in the tooth with arrested root development. A regenerative endodontic procedure that used a growth factor was performed for a necrotic molar with arrested root formation in a 20-year-old patient. Thorough disinfection by using mechanical instrumentation and copious irrigation of antimicrobial agents as well as intracanal medication with calcium hydroxide was performed throughout the first 2 appointments. At the third appointment, the root canals were irrigated with an antimicrobial solution and 17% EDTA, and bleeding was evoked by passing sterile paper points beyond the apex in each canal. Small pieces of a collagen membrane saturated with rhPDGF-BB solution from GEM 21S were packed into each canal. Mineral trioxide aggregate was placed, and Cavit and composite resin were used to restore the tooth. Complete root maturation and resolution of a periapical radiolucency were observed at the 15-month follow-up. The present report presents a regenerative endodontic procedure that uses rhPDGF-BB for a necrotic molar with arrested root development. The finding of continued root development in the present case suggests that regenerative endodontic treatment may be able to resume the root maturation process in teeth with arrested root formation. Further clinical studies are required to investigate the efficacy of rhPDGF-BB in regenerative endodontic treatment. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    V. Vucic

    2006-02-01

    Full Text Available Gamma-irradiation (gamma-IR is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD, specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001 antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control to 49% (IR cells, with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

  17. Supernovae and high density nuclear matter

    Energy Technology Data Exchange (ETDEWEB)

    Kahana, S.

    1986-01-01

    The role of the nuclear equation of state (EOS) in producing prompt supernova explosions is examined. Results of calculations of Baron, Cooperstein, and Kahana incorporating general relativity and a new high density EOS are presented, and the relevance of these calculations to laboratory experiments with heavy ions considered. 31 refs., 6 figs., 2 tabs.

  18. High Density GEOSAT/GM Altimeter Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The high density Geosat/GM altimeter data south of 30 S have finally arrived. In addition, ERS-1 has completed more than 6 cycles of its 35-day repeat track. These...

  19. Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1 in hepatic cell proliferation at mononucleosomal resolution.

    Directory of Open Access Journals (Sweden)

    Natalia Sacilotto

    Full Text Available BACKGROUND: Gas1 (growth arrest-specific 1 gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real time by quantifying the presence of RNA polymerase II in coding regions (RNApol-ChIP. It has been found that Gas1 is expressed not only in quiescent liver but also at the cell cycle G(1/S transition. The latter expression peak had not been previously reported. Two nucleosomes, flanking a nucleosome-free region, are positioned close to the transcription start site. Both nucleosomes slide in going from the active to the inactive state and vice versa. Nuc-ChIP analysis of the acquisition of histone epigenetic marks show distinctive features in both active states: H3K9ac and H3K4me2 are characteristic of transcription in G(0 and H4R3me2 in G(1/S transition. Sequential-ChIP analysis revealed that the "repressing" mark H3K9me2 colocalize with several "activating" marks at nucleosome N-1 when Gas1 is actively transcribed suggesting a greater plasticity of epigenetic marks than proposed until now. The recruitment of chromatin-remodeling or modifying complexes also displayed distinct characteristics in quiescence and the G(1/S transition. CONCLUSIONS/SIGNIFICANCE: The finding that Gas1 is transcribed at the G(1/S transition suggests that the gene may exert a novel function during cell proliferation. Transcription of this gene is modulated by specific "activating" and

  20. Sarsaparilla (Smilax Glabra Rhizome) Extract Inhibits Cancer Cell Growth by S Phase Arrest, Apoptosis, and Autophagy via Redox-Dependent ERK1/2 Pathway.

    Science.gov (United States)

    She, Tiantian; Qu, Like; Wang, Lixin; Yang, Xingxin; Xu, Shuo; Feng, Junnan; Gao, Yujing; Zhao, Chuanke; Han, Yong; Cai, Shaoqing; Shou, Chengchao

    2015-05-01

    Cancer is still the major cause of death across the world. Regular approaches cannot effectively solve the emerging problems, including drug/radiation resistance, side effects, and therapeutic ineffectiveness. Natural dietary supplements have shown effectiveness in the prevention and treatment of cancer. Sarsaparilla (Smilax Glabra Rhizome) has growth-inhibitory effects on several cancer cell lines in vitro and in vivo, with little toxicity on normal cells. However, the mechanism underlying its function remains elusive. In the present study, we examined the anticancer activity of the supernatant of the water-soluble extract (SW) from sarsaparilla. Liquid chromatography/mass spectrometry-ion trap-time-of-flight (LC/MS-IT-TOF) analysis identified flavonoids, alkaloids, and phenylpropanoids as the major bioactive components of SW. SW was shown to markedly inhibit the growth of a broad spectrum of cancer cell lines in the in vitro and in vivo assays. S phase arrest, autophagy, or/and apoptosis were partly responsible for SW-induced growth inhibition. Results of microarray analysis and validation by quantitative RT-PCR indicated the involvement of oxidative stress and the MAPK1 pathway in SW-treated cells. We further found that SW destroyed intracellular-reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and supplement with N-acetylcysteine (NAC) or glutathione (GSH) significantly antagonized SW-induced S phase arrest, apoptosis, and autophagy. In addition, SW-induced GSH/GSSG imbalance activated the ERK1/2 pathway, which contributed to SW-induced S phase arrest, apoptosis, autophagy, and resultant growth-inhibitory effect. Together, our results provide a molecular basis for sarsaparilla as an anticancer agent.

  1. Growth inhibitory effect of KYKZL-1 on Hep G{sub 2} cells via inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jing; Du, Yi-Fang; Xiao, Zhi-Yi; Pan, Li-Li; Li, Wei; Huan, Lin; Gong, Zhu-Nan [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Wei, Shao-Hua [College of Chemistry and Materials Science, Nanjing Normal University, Nanjing (China); Huang, Shi-Qian; Xun, Wei; Zhang, Yi; Chang, Lei-Lei; Xie, Meng-Yu [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Ao, Gui-Zhen [Department of Medicinal Chemistry, School of Pharmacy, Soochow University, Jiangsu (China); Cai, Jie; Qiu, Ting; Wu, Hao; Sun, Ting [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Xu, Guang-Lin, E-mail: xudunlop@126.com [Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing (China); Department of Pharmacology, University of Michigan, Ann Arbor (United States)

    2014-01-01

    KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the inhibitory activity test on Hep G{sub 2} growth. We found that KYKZL-1 inhibited the growth of Hep G{sub 2} cells via inducing apoptosis. Further studies showed that KYKZL-1 activated caspase-3 through cytochrome c release from mitochondria and down regulation of Bcl-2/Bax ratio and reduced the high level of COX-2 and 5-LOX. As shown in its anti-inflammatory effect, KYKZL-1 also exhibited inhibitory effect on the PGE{sub 2} and LTB{sub 4} production in Hep G{sub 2} cells. Accordingly, exogenous addition of PGE{sub 2} or LTB{sub 4} reversed the decreases in cell viability. In addition, KYKZL-1 caused cell cycle arrest at the S–G{sub 2} checkpoint via the activation of p21{sup CIP1} protein and down-regulation of cyclin A expression. These data indicate that the growth inhibitory effect of KYKZL-1 is associated with inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest. Combined with our previous findings, KYKZL-1 exhibiting COX/5-LOX inhibition may be a promising potential agent not only for inflammation control but also for cancer prevention/therapy with an enhanced gastric safety profile. - Highlights: • KYKZL-1 is designed to exhibit COX/5-LOX dual inhibition. • KYKZL-1 resulted in apoptosis of Hep G{sub 2} cells. • KYKZL-1 activated caspase-3 through cytochrome c and bcl-2/bax ratio. • KYKZL-1 caused cell cycle arrest via modulation of p21{sup CIP1} and cyclin A level.

  2. The high density Z-pinch

    Energy Technology Data Exchange (ETDEWEB)

    McCall, G.H.

    1988-01-01

    During the past few years techniques have been developed for producing pinches in solid deuterium. The conditions which exist in these plasmas are quiet different from those produced earlier. The pinch is formed from a fiber of solid deuterium rather than from a low density gas, and the current is driven by a low impedance, high voltage pulse generator. Because of the high initial density, it is not necessary to compress the pinch to reach thermonuclear conditions, and the confinement time required for energy production is much shorter than for a gas. The experimental results, which have been verified by experiments performed at higher current were quite surprising and encouraging. The pinch appeared to be stable for a time much longer than the Alfven radial transit time. In this paper, however, I argue that the pinch is not strictly stable, but it does not appear to disassemble in a catastrophic fashion. It appears that there may be a distinction between stability and confinement in the high density pinch. In the discussion below I will present the status of the high density Z-pinch experiments at laboratories around the world, and I will describe some of the calculational and experimental results. I will confine my remarks to recent work on the high density pinch. 17 refs. 10 figs.

  3. Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.

    Science.gov (United States)

    Cai, Xianbin; Hu, Xi; Tan, Xiaojun; Cheng, Weijie; Wang, Qinjia; Chen, Xiaofeng; Guan, Yinghong; Chen, Chong; Jing, Xubin

    2015-01-01

    Esophageal squamous cell carcinomas (ESCC) have become a severe threat to health and the current treatments for ESCC are frequently not effective. Recent epidemiological studies suggest that the anti-hyperglycemic agent metformin may reduce the risk of developing cancer, including ESCC, among diabetic patients. However, the antitumor effects of metformin on ESCC and the mechanisms underlying its cell cycle regulation remain elusive. The findings reported herein show that the anti-proliferative action of metformin on ESCC cell lines is partially mediated by AMPK. Moreover, we observed that metformin induced G0/G1 phase arrest accompanied by the up-regulation of p21CIP1 and p27KIP1. In vivo experiments further showed that metformin inhibited tumor growth in a ESCC xenograft model. Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo. In conclusion, metformin inhibits the growth of ESCC cells both in cell cultures and in an animal model. AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC. These findings indicate that metformin has the potential for use in the treatment of ESCC.

  4. Effects of 50 Hz pulsed electromagnetic fields on the growth and cell cycle arrest of mesenchymal stem cells: an in vitro study.

    Science.gov (United States)

    Li, Xinping; Zhang, Mingsheng; Bai, Liming; Bai, Wenfang; Xu, Weicheng; Zhu, Hongxiang

    2012-12-01

    Mesenchymal stem cells (MSCs) are capable of self-renew and multipotent differatiation which allows them to be sensitive to microenvironment is altered. Pulsed electromagnetic fields (PEMF) can affect cellular physiology of some types of cells. This study was undertaken to investigate the effects of PEMF on the growth and cell cycle arrest of MSCs expanded in vitro. To achieve this, cultured of normal rat MSCs, the treatment groups were respectively irradiated by 50 Hz PEMF at 10 mT of flux densities for 3 or 6 h. The effects of PEMF on cell proliferation, cell cycle arrest, and cell surface antigen phenotype were investigated. Our results showed that exposed MSCs had a significant proliferative capacity (P cell growth was not different (P>0.05) at an earlier phase after PEMF treatment. Exposure to PEMF had a significant increase the percentage of MSCs in G1 phase compare with the control group, with a higher percentage of cells in G1 phase exposed for 6 h then that for 3 h. At the 16th hour after treatment, PEMF had no significant effect on cell proliferation and cell cycle (P>0.05). These results suggested that PEMF enhanced MSCs proliferation with time-independent and increased the percentage of cells at the G1 phase of the cell cycle in a time-dependent manner, and the effect of PEMF on the cell proliferation and cell cycle arrest of MSCs was temporal after PEMF treatment.

  5. Two-color QCD at high density

    Energy Technology Data Exchange (ETDEWEB)

    Boz, Tamer; Skullerud, Jon-Ivar [Department of Mathematical Physics, Maynooth University, Maynooth, Co. Kildare (Ireland); Centre for the Subatomic Structure of Matter, Adelaide University, Adelaide, SA 5005 (Australia); Giudice, Pietro [Universität Münster, Institut für Theoretische Physik, Münster (Germany); Hands, Simon [Department of Physics, College of Science, Swansea University, Swansea (United Kingdom); Williams, Anthony G. [Centre for the Subatomic Structure of Matter, Adelaide University, Adelaide, SA 5005 (Australia)

    2016-01-22

    QCD at high chemical potential has interesting properties such as deconfinement of quarks. Two-color QCD, which enables numerical simulations on the lattice, constitutes a laboratory to study QCD at high chemical potential. Among the interesting properties of two-color QCD at high density is the diquark condensation, for which we present recent results obtained on a finer lattice compared to previous studies. The quark propagator in two-color QCD at non-zero chemical potential is referred to as the Gor’kov propagator. We express the Gor’kov propagator in terms of form factors and present recent lattice simulation results.

  6. Spin polarization in high density quark matter

    DEFF Research Database (Denmark)

    Bohr, Henrik; Panda, Prafulla K.; Providênci, Constanca

    2013-01-01

    We investigate the occurrence of a ferromagnetic phase transition in high density hadronic matter (e.g., in the interior of a neutron star). This could be induced by a four-fermion interaction analogous to the one which is responsible for chiral symmetry breaking in the Nambu-Jona-Lasinio model......, to which it is related through a Fierz transformation. Flavor SU(2) and flavor SU(3) quark matter are considered. A second-order phase transition is predicted at densities about 5 times the normal nuclear matter density. It is also found that in flavor SU(3) quark matter, a first-order transition from...

  7. Method of high-density foil fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Blue, Craig A.; Sikka, Vinod K.; Ohriner, Evan K.

    2003-12-16

    A method for preparing flat foils having a high density includes the steps of mixing a powdered material with a binder to form a green sheet. The green sheet is exposed to a high intensity radiative source adapted to emit radiation of wavelengths corresponding to an absorption spectrum of the powdered material. The surface of the green sheet is heated while a lower sub-surface temperature is maintained. An apparatus for preparing a foil from a green sheet using a radiation source is also disclosed.

  8. Fibroblast growth factor 2 causes G2/M cell cycle arrest in ras-driven tumor cells through a Src-dependent pathway.

    Directory of Open Access Journals (Sweden)

    Jacqueline Salotti

    Full Text Available We recently reported that paracrine Fibroblast Growth Factor 2 (FGF2 triggers senescence in Ras-driven Y1 and 3T3(Ras mouse malignant cell lines. Here, we show that although FGF2 activates mitogenic pathways in these Ras-dependent malignant cells, it can block cell proliferation and cause a G2/M arrest. These cytostatic effects of FGF2 are inhibited by PD173074, an FGF receptor (FGFR inhibitor. To determine which downstream pathways are induced by FGF2, we tested specific inhibitors targeting mitogen-activated protein kinase (MEK, phosphatidylinositol 3 kinase (PI3K and protein kinase C (PKC. We show that these classical mitogenic pathways do not mediate the cytostatic activity of FGF2. On the other hand, the inhibition of Src family kinases rescued Ras-dependent malignant cells from the G2/M irreversible arrest induced by FGF2. Taken together, these data indicate a growth factor-sensitive point in G2/M that likely involves FGFR/Ras/Src pathway activation in a MEK, PI3K and PKC independent manner.

  9. The MicroRNA 424/503 Cluster Reduces CDC25A Expression during Cell Cycle Arrest Imposed by Transforming Growth Factor β in Mammary Epithelial Cells

    Science.gov (United States)

    Rodriguez-Barrueco, Ruth; de la Iglesia-Vicente, Janis; Olivan, Mireia; Castro, Veronica; Saucedo-Cuevas, Laura; Marshall, Netonia; Putcha, Preeti; Castillo-Martin, Mireia; Bardot, Evan; Ezhkova, Elena; Iavarone, Antonio; Cordon-Cardo, Carlos

    2014-01-01

    Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor β (TGF-β) in the mammary epithelium. Induction of this microRNA cluster impacts mammary epithelium fate by regulating apoptosis and insulin-like growth factor 1 (IGF1) signaling. Here, we expanded our finding to demonstrate that miR-424(322)/503 is an integral component of the cell cycle arrest mediated by TGF-β. Mechanistically, we showed that after TGF-β exposure, increased levels of miR-424(322)/503 reduce the expression of the cell cycle regulator CDC25A. miR-424(322)/503-dependent posttranscriptional downregulation of CDC25A cooperates with previously described transcriptional repression of the CDC25A promoter and proteasome-mediated degradation to reduce the levels of CDC25A expression and to induce cell cycle arrest. We also provide evidence that the TGF-β/miR-424(322)/503 axis is part of the mechanism that regulates the proliferation of hormone receptor-positive (HR+) mammary epithelial cells in vivo. PMID:25266660

  10. The microRNA 424/503 cluster reduces CDC25A expression during cell cycle arrest imposed by transforming growth factor β in mammary epithelial cells.

    Science.gov (United States)

    Llobet-Navas, David; Rodriguez-Barrueco, Ruth; de la Iglesia-Vicente, Janis; Olivan, Mireia; Castro, Veronica; Saucedo-Cuevas, Laura; Marshall, Netonia; Putcha, Preeti; Castillo-Martin, Mireia; Bardot, Evan; Ezhkova, Elena; Iavarone, Antonio; Cordon-Cardo, Carlos; Silva, Jose M

    2014-12-01

    Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor β (TGF-β) in the mammary epithelium. Induction of this microRNA cluster impacts mammary epithelium fate by regulating apoptosis and insulin-like growth factor 1 (IGF1) signaling. Here, we expanded our finding to demonstrate that miR-424(322)/503 is an integral component of the cell cycle arrest mediated by TGF-β. Mechanistically, we showed that after TGF-β exposure, increased levels of miR-424(322)/503 reduce the expression of the cell cycle regulator CDC25A. miR-424(322)/503-dependent posttranscriptional downregulation of CDC25A cooperates with previously described transcriptional repression of the CDC25A promoter and proteasome-mediated degradation to reduce the levels of CDC25A expression and to induce cell cycle arrest. We also provide evidence that the TGF-β/miR-424(322)/503 axis is part of the mechanism that regulates the proliferation of hormone receptor-positive (HR(+)) mammary epithelial cells in vivo.

  11. Analysis on environmental factors of embryo growth arrest%胚胎停止发育的环境影响因素分析

    Institute of Scientific and Technical Information of China (English)

    杨正爱; 田旭光

    2012-01-01

    目的:探讨各种环境因素对胚胎发育的影响,为预防胚胎停止发育提供依据.方法:采用自行设计的问卷进行调查,分析比较188例诊断为早期胚胎停止发育患者和281例正常流产妇女的一般情况、饮食习惯、生活习惯、家庭环境、职业环境、心理健康状况和人际关系对胚胎停止发育的影响.结果:单因素分析显示,年龄、怀孕次数、情绪控制能力、精神压力、值夜班、补充叶酸、是否饮茶、是否吸烟、携带手机时间、使用微波炉或电磁炉、接触震动及接触电磁辐射是胚胎停止发育的影响因素(P<0.05);多因素分析显示,补充叶酸(OR=2.514)、是否吸烟(OR=4.254)及接触电磁辐射(OR=4.998)是主要影响因素.结论:胚胎停止发育是多种因素综合影响的结果.孕期叶酸的补充、戒烟及远离电磁辐射是重要的预防措施.%Objective; To explore the effect of various environmental factors on embryonic development, provide a basis for preventing embryo growth arrest. Methods: A self - designed questionnaire was used to survey, analyze, and compare the effects of general condition, dietary habits, living habits, family environment, occupational environment, psychological health status, and interpersonal relationship of 188 patients diagnosed as early embryo growth arrest and 281 normal women undergoing abortion on embryo growth arrest Results: Univa-riate analysis showed that age, times of pregnancy, emotional control, stress, night shift, supplementing folic acid, tea - drinking or not, smoking or not, carrying mobile phones, using a microwave oven or cooker, exposure to vibration, and exposure to electromagnetic radiation were influencing factors of embryo growth arrest ( P < 0. 05 ) ; multivariate analysis showed that supplementing folic acid ( OR= 2. 514 ) , smoking or not ( OR = 4. 254) , and exposure to electromagnetic radiation ( OR = 4. 998 ) were main influencing factors. Conclusion

  12. Suppression of AKT anti-apoptotic signaling by a novel drug candidate results in growth arrest and apoptosis of hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Andrea Cuconati

    Full Text Available Hepatocellular carcinoma (HCC is the third most common cause of cancer fatalities worldwide, with limited treatment options and five year survival rates of between 50% growth inhibition by HBF-0079. In Huh7 cells, HBF-0079 induced cell cycle arrest in G1 and concomitant apoptosis, and its effects were irreversible after removal of the compound. These observations corroborate a loss of AKT phosphorylation at the mTORC2-targeted residue S473, with concurrent loss of phosphorylation of the mTORC1 targets SK6 and 4EBP1 in Huh7 but not PH5CH cells. Finally, growth of Hep3B-derived tumors in a murine xenograft model was significantly repressed by the compound through either systemic or intratumoral administration of formulated HBF-0079. The potential for development of this drug candidate is discussed.

  13. Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress.

    Science.gov (United States)

    Yaffe, Paul B; Power Coombs, Melanie R; Doucette, Carolyn D; Walsh, Mark; Hoskin, David W

    2015-10-01

    Piperine, a piperidine alkaloid present in black pepper, inhibits the growth of cancer cells, although the mechanism of action is not well understood. In this study, we show that piperine (75-150 µM) inhibited the growth of several colon cancer cell lines but had little effect on the growth of normal fibroblasts and epithelial cells. Piperine inhibited HT-29 colon carcinoma cell proliferation by causing G1 phase cell cycle arrest that was associated with decreased expression of cyclins D1 and D3 and their activating partner cyclin-dependent kinases 4 and 6, as well as reduced phosphorylation of the retinoblastoma protein and up-regulation of p21/WAF1 and p27/KIP1 expression. In addition, piperine caused hydroxyl radical production and apoptosis that was partially dependent on the production of reactive oxygen species. Piperine-treated HT-29 cells showed loss of mitochondrial membrane integrity and cleavage of poly (ADP-ribose) polymerase-1, as well as caspase activation and reduced apoptosis in the presence of the pan-caspase inhibitor zVAD-FMK. Increased expression of the endoplasmic reticulum stress-associated proteins inositol-requiring 1α protein, C/EBP homologous protein, and binding immunoglobulin protein, and activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, as well as decreased phosphorylation of Akt and reduced survivin expression were also observed in piperine-treated HT-29 cells. Furthermore, piperine inhibited colony formation by HT-29 cells, as well as the growth of HT-29 spheroids. Cell cycle arrest and endoplasmic reticulum stress-associated apoptosis following piperine treatment of HT-29 cells provides the first evidence that piperine may be useful in the treatment of colon cancer.

  14. Tanshinone IIA Inhibits Growth of Keratinocytes through Cell Cycle Arrest and Apoptosis: Underlying Treatment Mechanism of Psoriasis

    Directory of Open Access Journals (Sweden)

    Fu-Lun Li

    2012-01-01

    Full Text Available The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE, and flow cytometry methods. Apoptosis was partially blocked by the caspase-3 inhibitor Ac-DEVD-CHO. Mitochondrial regulation of apoptosis further downstream was investigated, showing changes in the mitochondrial membrane potential, cytochrome c release into the cytoplasm, and enhanced activation of cleaved caspase-3 and Poly ADP-ribose polymerase (PARP. There was also no translocation of apoptosis-inducing factor (AIF from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. Our findings provide the molecular mechanisms by which Tan IIA can be used to treat psoriasis and support the traditional use of Salvia miltiorrhiza Bungee (Labiatae for psoriasis and related skin diseases.

  15. Ground state of high-density matter

    Science.gov (United States)

    Copeland, ED; Kolb, Edward W.; Lee, Kimyeong

    1988-01-01

    It is shown that if an upper bound to the false vacuum energy of the electroweak Higgs potential is satisfied, the true ground state of high-density matter is not nuclear matter, or even strange-quark matter, but rather a non-topological soliton where the electroweak symmetry is exact and the fermions are massless. This possibility is examined in the standard SU(3) sub C tensor product SU(2) sub L tensor product U(1) sub Y model. The bound to the false vacuum energy is satisfied only for a narrow range of the Higgs boson masses in the minimal electroweak model (within about 10 eV of its minimum allowed value of 6.6 GeV) and a somewhat wider range for electroweak models with a non-minimal Higgs sector.

  16. Nanotechnology for Synthetic High Density Lipoproteins

    Science.gov (United States)

    Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

    2014-01-01

    Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

  17. Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway.

    Science.gov (United States)

    Wu, Chien-Ting; Lin, Tung-Yi; Hsu, Hsien-Yeh; Sheu, Fuu; Ho, Chau-Mei; Chen, Edmund I-T

    2011-12-01

    Ling Zhi-8 (LZ-8), an immunomodulatory protein, is derived from and has been cloned from the medicinal mushroom Ganoderma lucidum (Reishi or Ling Zhi); this protein exhibits immunomodulating and antitumor properties. We investigated the effects of recombinant LZ-8 protein (rLZ-8) on the proliferation of A549 human lung cancer cells. Here, we showed that rLZ-8 inhibits cell growth and that this is correlated with increased G(1) arrest. The treatment of A549 cells with rLZ-8 activated p53 and p21 expression, and both the G(1) arrest and the antigrowth effect were found to be p53 dependent. It was further demonstrated that rLZ-8 inhibited tumor growth in mice transplanted with Lewis lung carcinoma cells. Interestingly, rLZ-8 treatment was found to lead to nucleolar stress (or ribosomal stress) as evidenced by inhibition of precursor ribosomal RNA synthesis and reduced polysome formation in A549 cells. These changes resulted in an increasing binding of ribosomal protein S7 to MDM2 and a decreased interaction between MDM2 and p53. Taking these results together, we have identified a novel rLZ-8 antitumor function that positively modulates p53 via ribosomal stress and inhibits lung cancer cell growth in vitro and in vivo. Our current results suggest that rLZ-8 may have potential as a therapeutic intervention for the treatment of cancers that contain wild-type p53 and high expression of MDM2.

  18. Crescimento inicial de duas cultivares de cafeeiro adensado influenciado por níveis de irrigação localizada Initial growth of two high-density coffee tree cultivars influenced by drip irrigation levels

    Directory of Open Access Journals (Sweden)

    Márcio S. Santana

    2004-12-01

    Full Text Available O experimento foi conduzido na Fazenda Água Limpa, Universidade de Brasília, tendo como objetivo avaliar o crescimento das cultivares de café IAPAR-59 e Obatã, submetidas a cinco níveis de irrigação por gotejamento durante o primeiro ano de formação e estudar formas de manejo da água do solo. O delineamento experimental usado foi o de blocos completos ao acaso para o fator irrigação em parcelas, com o fator cultivar em subparcela e o fator tempo em dias após o transplante (dat em subsubparcela, com seis repetições. Os cinco níveis de irrigação foram tensões de 20; 40 e 60 kPa determinadas com o auxílio de tensiômetros, sistema Irrigas com tensão definida pelo próprio sensor e sem irrigação. As variáveis de crescimento avaliadas foram índice de área foliar, número de folhas, diâmetro do caule, altura de plantas e número de ramos plagiotrópicos. Aos 316 dat, os tratamentos irrigados tiveram o mesmo comportamento de crescimento, mas foram significativamente maiores em relação ao tratamento não irrigado. O sistema Irrigas mostrou ser uma opção para o manejo adequado da água com manutenção nula. As cultivares IAPAR-59 e Obatã têm comportamento de crescimento diferenciado, com todas as variáveis avaliadas favorecendo esta última.The experiment was carried out at "Água Limpa" Farm, University of Brasilia. The objective was to evaluate growth of IAPAR-59 and Obatã cultivars using five drip irrigation levels, during the crop of the first year and to study soil water management. It was used a randomized complete block design for the irrigation factor, with the cultivar factor as a split plot on irrigation and the factor time in days after transplanting (dat as a split plot on cultivar. The five irrigation levels were 20; 40 and 60 kPa, established using tensiometers; Irrigas system with soil water tension defined by its sensor; and no irrigation. Growth variables evaluated were leaf area index, leaf number

  19. 6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest.

    Science.gov (United States)

    Lin, Ching-Bin; Lin, Chun-Che; Tsay, Gregory J

    2012-01-01

    6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27(Kip1) and p21(Cip1) were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS) and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27(Kip1), and p21(Cip1) levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.

  20. 6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

    Directory of Open Access Journals (Sweden)

    Ching-Bin Lin

    2012-01-01

    Full Text Available 6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs, and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27Kip1 and p21Cip1 were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27Kip1, and p21Cip1 levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer.

  1. Crystallographic alignment of high-density gallium nitride nanowire arrays.

    Science.gov (United States)

    Kuykendall, Tevye; Pauzauskie, Peter J; Zhang, Yanfeng; Goldberger, Joshua; Sirbuly, Donald; Denlinger, Jonathan; Yang, Peidong

    2004-08-01

    Single-crystalline, one-dimensional semiconductor nanostructures are considered to be one of the critical building blocks for nanoscale optoelectronics. Elucidation of the vapour-liquid-solid growth mechanism has already enabled precise control over nanowire position and size, yet to date, no reports have demonstrated the ability to choose from different crystallographic growth directions of a nanowire array. Control over the nanowire growth direction is extremely desirable, in that anisotropic parameters such as thermal and electrical conductivity, index of refraction, piezoelectric polarization, and bandgap may be used to tune the physical properties of nanowires made from a given material. Here we demonstrate the use of metal-organic chemical vapour deposition (MOCVD) and appropriate substrate selection to control the crystallographic growth directions of high-density arrays of gallium nitride nanowires with distinct geometric and physical properties. Epitaxial growth of wurtzite gallium nitride on (100) gamma-LiAlO(2) and (111) MgO single-crystal substrates resulted in the selective growth of nanowires in the orthogonal [1\\[Evec]0] and [001] directions, exhibiting triangular and hexagonal cross-sections and drastically different optical emission. The MOCVD process is entirely compatible with the current GaN thin-film technology, which would lead to easy scale-up and device integration.

  2. Wogonoside induces growth inhibition and cell cycle arrest via promoting the expression and binding activity of GATA-1 in chronic myelogenous leukemia cells.

    Science.gov (United States)

    Li, Hui; Hui, Hui; Xu, Jingyan; Yang, Hao; Zhang, Xiaoxiao; Liu, Xiao; Zhou, Yuxin; Li, Zhiyu; Guo, Qinglong; Lu, Na

    2016-06-01

    GATA-1, a zinc finger transcription factor, has been demonstrated to play a key role in the progression of leukemia. In this study, we investigate the effects of wogonoside, a naturally bioactive flavonoid derived from Scutellaria baicalensis Georgi, on cell growth and cell cycle in chronic myeloid leukemia (CML) cells, and uncover its underlying mechanisms. The experimental design comprised CML cell lines K562, imatinib-resistant K562 (K562r) cells, and primary CML cells, treated in vitro or in vivo, respectively, with wogonoside; growth and cell cycle were then evaluated. We found that wogonoside could induce growth inhibition and G0/G1 cell cycle arrest in both normal and K562r cells. Wogonoside promotes the expression of GATA-1 and facilitates the binding to methyl ethyl ketone (MEK) and p21 promoter, thus inhibiting MEK/extracellular signal-regulated kinase signaling and cell cycle checkpoint proteins, including CDK2, CDK4, cyclin A, and cyclin D1, and increasing p21 expression. Furthermore, in vivo studies showed that administration of wogonoside decreased CML cells and prolonged survival in NOD/SCID mice with CML cell xenografts. In conclusion, these results clearly revealed the inhibitory effect of wogonoside on the growth in CML cells and suggested that wogonoside may act as a promising drug for the treatment of imatinib-resistant CML.

  3. A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.

    Directory of Open Access Journals (Sweden)

    Nan Hua

    Full Text Available Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs. In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.

  4. UV-B inhibition of hypocotyl growth in etiolated Arabidopsis thaliana seedlings is a consequence of cell cycle arrest initiated by photodimer accumulation.

    Science.gov (United States)

    Biever, Jessica J; Brinkman, Doug; Gardner, Gary

    2014-06-01

    Ultraviolet (UV) radiation is an important constituent of sunlight that determines plant morphology and growth. It induces photomorphogenic responses but also causes damage to DNA. Arabidopsis mutants of the endonucleases that function in nucleotide excision repair, xpf-3 and uvr1-1, showed hypersensitivity to UV-B (280-320nm) in terms of inhibition of hypocotyl growth. SOG1 is a transcription factor that functions in the DNA damage signalling response after γ-irradiation. xpf mutants that carry the sog1-1 mutation showed hypocotyl growth inhibition after UV-B irradiation similar to the wild type. A DNA replication inhibitor, hydroxyurea (HU), also inhibited hypocotyl growth in etiolated seedlings, but xpf-3 was not hypersensitive to HU. UV-B irradiation induced accumulation of the G2/M-specific cell cycle reporter construct CYCB1;1-GUS in wild-type Arabidopsis seedlings that was consistent with the expected accumulation of photodimers and coincided with the time course of hypocotyl growth inhibition after UV-B treatment. Etiolated mutants of UVR8, a recently described UV-B photoreceptor gene, irradiated with UV-B showed inhibition of hypocotyl growth that was not different from that of the wild type, but they lacked UV-B-specific expression of chalcone synthase (CHS), as expected from previous reports. CHS expression after UV-B irradiation was not different in xpf-3 compared with the wild type, nor was it altered after HU treatment. These results suggest that hypocotyl growth inhibition by UV-B light in etiolated Arabidopsis seedlings, a photomorphogenic response, is dictated by signals originating from UV-B absorption by DNA that lead to cell cycle arrest. This process occurs distinct from UVR8 and its signalling pathway responsible for CHS induction.

  5. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: in vitro and in vivo study.

    Science.gov (United States)

    Pandey, Mitali; Kaur, Parminder; Shukla, Sanjeev; Abbas, Ata; Fu, Pingfu; Gupta, Sanjay

    2012-12-01

    Apigenin (4',5,7,-trihydroxyflavone), an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms that have not been fully elucidated. Our studies indicate that apigenin-mediated growth inhibitory responses are due to inhibition of class I histone deacetylases (HDACs) in prostate cancer cells. Treatment of PC-3 and 22Rv1 cells with apigenin (20-40 µM) resulted in the inhibition of HDAC enzyme activity, specifically HDAC1 and HDAC3 at the protein and message level. Apigenin-mediated HDAC inhibition resulted in global histone H3 and H4 acetylation, as well as localized hyperacetylation of histone H3 on the p21/waf1 promoter. A corresponding increase was observed in p21/waf1 and bax protein and mRNA expression after apigenin exposure, consistent with the use of HDAC inhibitor, trichostatin A. The downstream events demonstrated cell cycle arrest and induction of apoptosis in both cancer cells. Studies of PC-3 xenografts in athymic nude mice further demonstrated that oral intake of apigenin at doses of 20 and 50 µg/mouse/d over an 8-wk period resulted in a marked reduction in tumor growth, HDAC activity, and HDAC1 and HDAC3 protein expression at both doses of apigenin. An increase in p21/waf1 expression was observed in apigenin-fed mice, compared to the control group. Furthermore, apigenin intake caused a significant decrease in bcl2 expression with concomitant increase in bax, shifting the bax/bcl2 ratio in favor of apoptosis. Our findings confirm for the first time that apigenin inhibits class I HDACs, particularly HDAC1 and HDAC3 and its exposure results in reversal of aberrant epigenetic events that promote malignancy. © 2011 Wiley Periodicals, Inc. Copyright © 2011 Wiley Periodicals, Inc.

  6. Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

    Science.gov (United States)

    Zhang, Jian; Wei, Wei; Jin, Hui-Cheng; Ying, Rong-Chao; Zhu, A-Kao; Zhang, Fang-Jie

    2015-01-01

    Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

  7. Nanobiotechnology applications of reconstituted high density lipoprotein.

    Science.gov (United States)

    Ryan, Robert O

    2010-12-01

    High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions.

  8. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  9. HIGH DENSITY QCD WITH HEAVY-IONS

    CERN Multimedia

    The Addendum 1 to Volume 2 of the CMS Physics TDR has been published The Heavy-Ion analysis group completed the writing of a TDR summarizing the CMS plans in using heavy ion collisions to study high density QCD. The document was submitted to the LHCC in March and presented in the Open Session of the LHCC on May 9th. The study of heavy-ion physics at the LHC is promising to be very exciting. LHC will open a new energy frontier in ultra-relativistic heavy-ion physics. The collision energy of heavy nuclei at sNN = 5.5 TeV will be thirty times larger than what is presently available at RHIC. We will certainly probe quark and gluon matter at unprecedented values of energy density. The prime goal of this research programme is to study the fundamental theory of the strong interaction - Quantum Chromodynamics (QCD) - in extreme conditions of temperature, density and parton momentum fraction (low-x). Such studies, with impressive experimental and theoretical advances in recent years thanks to the wealth of high-qua...

  10. Recycling of irradiated high-density polyethylene

    Science.gov (United States)

    Navratil, J.; Manas, M.; Mizera, A.; Bednarik, M.; Stanek, M.; Danek, M.

    2015-01-01

    Radiation crosslinking of high-density polyethylene (HDPE) is a well-recognized modification of improving basic material characteristics. This research paper deals with the utilization of electron beam irradiated HDPE (HDPEx) after the end of its lifetime. Powder of recycled HDPEx (irradiation dose 165 kGy) was used as a filler into powder of virgin low-density polyethylene (LDPE) in concentrations ranging from 10% to 60%. The effect of the filler on processability and mechanical behavior of the resulting mixtures was investigated. The results indicate that the processability, as well as mechanical behavior, highly depends on the amount of the filler. Melt flow index dropped from 13.7 to 0.8 g/10 min comparing the lowest and the highest concentration; however, the higher shear rate the lower difference between each concentration. Toughness and hardness, on the other hand, grew with increasing addition of the recycled HDPEx. Elastic modulus increased from 254 to 450 MPa and material hardness increased from 53 to 59 ShD. These results indicate resolving the problem of further recycling of irradiated polymer materials while taking advantage of the improved mechanical properties.

  11. Galaxy interactions II: High density environments

    CERN Document Server

    Alonso, Sol; Padilla, Nelson; Lambas, Diego G

    2011-01-01

    With the aim to assess the role of dense environments in galaxy interactions, properties we present an analysis of close galaxy pairs in groups and clusters, obtained from the Sloan Digital Sky Survey Data Release 7 (SDSS-DR7). We identified pairs that reside in groups by cross-correlating the total galaxy pair catalogue with the SDSS-DR7 group catalogue from Zapata et al. (2009). We classify pair galaxies according to the intensity of interaction. We analysed the effect of high density environments on different classes of galaxy-galaxy interactions and we have also studied the impact of the group global environment on pair galaxies. We find that galaxy pairs are more concentrated towards the group centres with respect to the other group galaxy members, and disturbed pairs show a preference to contain the brightest galaxy in the groups. The color-magnitude relation exhibits significant differences between pair galaxies and the control sample, consisting in color tails with a clear excess of extremely blue and...

  12. Strangeness production in high density baryon matter

    CERN Document Server

    Ganz, R E

    1999-01-01

    Strangeness production in heavy-ion collisions, when compared to proton proton collisions, is potentially a sensitive probe for collective energy deposition and therefore for reaction mechanisms in general. It may therefore provide insight into possible QGP formation in dense nuclear matter. To establish an understanding of the observed yields, a systematic study of high density baryon matter at different beam energies is essential. This might also reveal possible discontinuities in the energy dependence of the reaction mechanism. We present preliminary results for kaon production in Au+Au collisions at beam kinetic energies of 6, 8, and 10.7 GeV/u obtained by the E917 experiment at the AGS (BNL). These measurements complement those carried out by the E866 collaboration at 2, 4, and 10.7 GeV/u with a significantly enlarged data sample. In both experiments a large range of rapidities was covered by taking data at different angular settings of the magnetic spectrometer.

  13. Abnormal high density lipoproteins in cerebrotendinous xanthomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Shore, V. (Lawrence Livermore Lab., CA); Salen, G.; Cheng, F.W.; Forte, T.; Shefer, S.; Tint, G.S.

    1981-11-01

    The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +/- 3.2 mg/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl esters are low, free cholesterol and phospholipids essentially normal, and triglycerides increased. The ratio of apoprotein (apo) to total cholesterol in the HDL of CTX was two to three times greater than normal. In the CTX HDL, the ratio of apoAI to apoAII was high, the proportion of apoC low, and a normally minor form of apoAI increased relative to other forms. The HDL in electron micrographs appeared normal morphologically and in particle size. The adnormalities in lipoprotein distribution profiles and composition of the plasma HDL result from metabolic defects that are not understood but may be linked to the genetic defect in bile acid synthesis in CTX. As a consequence, it is probable that the normal functions of the HDL, possibly including modulation of LDL-cholesterol uptake and the removal of excess cholesterol from peripheral tissues, are perturbed significantly in this disease.

  14. High-density electroencephalography developmental neurophysiological trajectories.

    Science.gov (United States)

    Dan, Bernard; Pelc, Karine; Cebolla, Ana M; Cheron, Guy

    2015-04-01

    Efforts to document early changes in the developing brain have resulted in the construction of increasingly accurate structural images based on magnetic resonance imaging (MRI) in newborn infants. Tractography diagrams obtained through diffusion tensor imaging have focused on white matter microstructure, with particular emphasis on neuronal connectivity at the level of fibre tract systems. Electroencephalography (EEG) provides a complementary approach with more direct access to brain electrical activity. Its temporal resolution is excellent, and its spatial resolution can be enhanced to physiologically relevant levels, through the combination of high-density recordings (e.g. by using 64 channels in newborn infants) and mathematical models (e.g. inverse modelling computation), to identify generators of different oscillation bands and synchrony patterns. The integration of functional and structural topography of the neonatal brain provides insights into typical brain organization, and the deviations seen in particular contexts, for example the effect of hypoxic-ischaemic insult in terms of damage, eventual reorganization, and functional changes. Endophenotypes can then be used for pathophysiological reasoning, management planning, and outcome measurements, and allow a longitudinal approach to individual developmental trajectories. © The Authors. Journal compilation © 2015 Mac Keith Press.

  15. The adenovirus E4orf4 protein induces growth arrest and mitotic catastrophe in H1299 human lung carcinoma cells.

    Science.gov (United States)

    Li, S; Szymborski, A; Miron, M-J; Marcellus, R; Binda, O; Lavoie, J N; Branton, P E

    2009-01-22

    The human adenovirus E4orf4 protein, when expressed alone, induces p53-independent death in a wide range of cancer cells. Earlier studies by our groups suggested that although in some cases cell death can be associated with some hallmarks of apoptosis, it is not always affected by caspase inhibitors. Thus it is unlikely that E4orf4-induced cell death occurs uniquely through apoptosis. In the present studies using H1299 human lung carcinoma cells as a model system we found that death is induced in the absence of activation of any of the caspases tested, accumulation of reactive oxygen species, or release of cytochrome c from mitochondria. E4orf4 caused a substantial change in cell morphology, including vigorous membrane blebbing, multiple nuclei in many cells and increased cell volume. Most of these characteristics are not typical of apoptosis, but they are of necrosis. FACS analysis and western blotting for cell cycle markers showed that E4orf4-expressing cells became arrested in G(2)/M and also accumulated high levels of cyclin E. The presence of significant numbers of tetraploid and polyploid cells and some cells with micronuclei suggested that E4orf4 appears to induce death in these cells through a process resulting from mitotic catastrophe.

  16. Neferine, an alkaloid from lotus seed embryo, inhibits human lung cancer cell growth by MAPK activation and cell cycle arrest.

    Science.gov (United States)

    Poornima, Paramasivan; Weng, Ching Feng; Padma, Viswanadha Vijaya

    2014-01-01

    Neferine is the major bisbenzylisoquinoline alkaloid isolated from the seed embryo of a traditional medicinal plant Nelumbo nucifera (Lotus). Epidemiological studies have revealed the therapeutic potential of lotus seed embryo. Although several mechanisms have been proposed, a clear anticancer action mechanism of neferine on lung cancer cells is still not known. Lung cancer is the most common cause of cancer death in the world, and the patients with advanced stage of nonsmall lung cancer require adjunct chemotherapy after surgical resection for the eradication of cancer cells. In this study, the effects of neferine were evaluated and characterized in A549 cells. Neferine induced apoptosis in a dose-dependent manner with the hypergeneration of reactive oxygen species, activation of MAPKs, lipid peroxidation, depletion of cellular antioxidant pool, loss of mitochondrial membrane potential, and intracellular calcium accumulation. Furthermore, neferine treatment leads to the inhibition of nuclear factor kappaB and Bcl2, upregulation of Bax and Bad, release of cytochrome C, activation of caspase cascade, and DNA fragmentation. In addition, neferine could induce p53 and its effector protein p21 and downregulation of cell cycle regulatory protein cyclin D1 thereby inducing G1 cell cycle arrest. These results suggest a novel function of neferine as an apoptosis inducer in lung cancer cells.

  17. Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression.

    Science.gov (United States)

    Armistead, Joy; Patel, Nehal; Wu, Xiaoli; Hemming, Richard; Chowdhury, Biswajit; Basra, Gagandeep Singh; Del Bigio, Marc R; Ding, Hao; Triggs-Raine, Barbara

    2015-05-01

    Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G, p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to characterize the effects of EMG1 deficiency, particularly in the brain, where EMG1 expression is high. Embryos homozygous for the mutation in Emg1 were small for gestational age with neural tube defects, and died between embryonic days 8.5 and 12.5. These embryos exhibited dramatically reduced cell proliferation, which we also detected in autopsy brain tissue and bone marrow of BCS patients, consistent with a requirement for high levels of EMG1 in tissues with rapid cell proliferation. In fibroblasts derived from the BCS mouse embryos, we detected a high proportion of binucleated cells, indicating that a mitotic defect underlies the growth arrest in BCS. These studies add to growing evidence of a link between ribosome biogenesis, mitotic progression, and brain development that is currently unexplored.

  18. 14 CFR 93.123 - High density traffic airports.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false High density traffic airports. 93.123... (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES High Density Traffic Airports § 93.123 High density traffic airports. (a) Each of the following airports is designated as a...

  19. Natural Variation in Small Molecule–Induced TIR-NB-LRR Signaling Induces Root Growth Arrest via EDS1- and PAD4-Complexed R Protein VICTR in Arabidopsis[C][W

    Science.gov (United States)

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E.; Gassmann, Walter; Schroeder, Julian I.

    2012-01-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor–nucleotide binding–Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid–induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest. PMID:23275581

  20. High Density Lipoprotein Metabolism in Man

    Science.gov (United States)

    Blum, Conrad B.; Levy, Robert I.; Eisenberg, Shlomo; Hall, Marshall; Goebel, Robert H.; Berman, Mones

    1977-01-01

    The turnover of 125I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous 125I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet. Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma

  1. Expansion of Endothelial Progenitor Cells in High Density Dot Culture of Rat Bone Marrow Cells

    Science.gov (United States)

    Wang, Ling; Kretlow, James D.; Zhou, Guangdong; Cao, Yilin; Liu, Wei; Zhang, Wen Jie

    2014-01-01

    In vitro expansion of endothelial progenitor cells (EPCs) remains a challenge in stem cell research and its application. We hypothesize that high density culture is able to expand EPCs from bone marrow by mimicking cell-cell interactions of the bone marrow niche. To test the hypothesis, rat bone marrow cells were either cultured in high density (2×105 cells/cm2) by seeding total 9×105 cells into six high density dots or cultured in regular density (1.6×104 cells/cm2) with the same total number of cells. Flow cytometric analyses of the cells cultured for 15 days showed that high density cells exhibited smaller cell size and higher levels of marker expression related to EPCs when compared to regular density cultured cells. Functionally, these cells exhibited strong angiogenic potentials with better tubal formation in vitro and potent rescue of mouse ischemic limbs in vivo with their integration into neo-capillary structure. Global gene chip and ELISA analyses revealed up-regulated gene expression of adhesion molecules and enhanced protein release of pro-angiogenic growth factors in high density cultured cells. In summary, high density cell culture promotes expansion of bone marrow contained EPCs that are able to enhance tissue angiogenesis via paracrine growth factors and direct differentiation into endothelial cells. PMID:25254487

  2. Novel ent-Kaurane Diterpenoid from Rubus corchorifolius L. f. Inhibits Human Colon Cancer Cell Growth via Inducing Cell Cycle Arrest and Apoptosis.

    Science.gov (United States)

    Chen, Xuexiang; Wu, Xian; Ouyang, Wen; Gu, Min; Gao, Zili; Song, Mingyue; Chen, Yunjiao; Lin, Yanyin; Cao, Yong; Xiao, Hang

    2017-03-01

    The tender leaves of Rubus corchorifolius L. f. have been consumed as tea for drinking in China since ancient times. In this study, a novel ent-kaurane diterpenoid was isolated and identified from R. corchorifolius L. f. leaves as ent-kaur-2-one-16β,17-dihydroxy-acetone-ketal (DEK). DEK suppressed the growth of HCT116 human colon cancer cells with an IC50 value of 40 ± 0.21 μM, while it did not cause significant growth inhibition on CCD-18Co human colonic myofibroblasts at up to100 μM. Moreover, DEK induced extensive apoptosis and S phase cell cycle arrest in the colon cancer cells. Accordingly, DEK caused profound effects on multiple signaling proteins associated with cell proliferation, cell death, and inflammation. DEK significantly upregulated the expression levels of pro-apoptotic proteins such as cleaved caspase-3, cleaved caspase-9, cleaved PARP, p53, Bax, and tumor suppressor p21(Cip1/Waf1), downregulated the levels of cell cycle regulating proteins such as cyclinD1, CDK2, and CDK4 and carcinogenic proteins such as EGFR and COX-2, and suppressed the activation of Akt. Overall, our results provide a basis for using DEK as a potential chemopreventive agent against colon carcinogenesis.

  3. New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells

    Science.gov (United States)

    Rossi, Alessandra; Schenone, Silvia; Angelucci, Adriano; Cozzi, Martina; Caracciolo, Valentina; Pentimalli, Francesca; Puca, Andrew; Pucci, Biagio; La Montagna, Raffaele; Bologna, Mauro; Botta, Maurizio; Giordano, Antonio

    2010-01-01

    Medulloblastoma is the most common malignant brain tumor in children, and despite improvements in the overall survival rate, it still lacks an effective treatment. Src plays an important role in cancer, and recently high Src activity was documented in medulloblastoma. In this report, we examined the effects of novel pyrazolo-[3,4-d]-pyrimidine derivative Src inhibitors in medulloblastoma. By MTS assay, we showed that the pyrimidine derivatives indicated as S7, S29, and SI163 greatly reduce the growth rate of medulloblastoma cells by inhibiting Src phosphorylation, compared with HT22 non-neoplastic nerve cells. These compounds also halt cells in the G2/M phase, and this effect likely occurs through the regulation of cdc2 and CDC25C phosphorylation, as shown by Western blot. Moreover, the exposure to pyrimidine derivatives induces apoptosis, assayed by the supravital propidium iodide assay, through modulation of the apoptotic proteins Bax and Bcl2, and inhibits tumor growth in vivo in a mouse model. Notably, S7, S29, and SI163 show major inhibitory effects on medulloblastoma cell growth compared with the chemotherapeutic agents cisplatin and etoposide. In conclusion, our results suggest that S7, S29, and SI163 could be novel attractive candidates for the treatment of medulloblastoma or tumors characterized by high Src activity.—Rossi, A., Schenone, S., Angelucci, A., Cozzi, M., Caracciolo, V., Pentimalli, F., Puca, A., Pucci, B., La Montagna, R., Bologna, M., Botta, M., Giordano, A. New pyrazolo-[3,4-d]-pyrimidine derivative Src kinase inhibitors lead to cell cycle arrest and tumor growth reduction of human medulloblastoma cells. PMID:20354138

  4. Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development

    DEFF Research Database (Denmark)

    Migliorini, Domenico; Lazzerini Denchi, Eros; Danovi, Davide

    2002-01-01

    characterized by overall growth deficiency, anemia, improper neural tube closure, and dilation of lateral ventricles. In situ analysis demonstrated increased levels of p21(CIP1/Waf1) and lower levels of Cyclin E and proliferating cell nuclear antigen expression. Consistent with lack of 5-bromo-2'-deoxyuridine...

  5. Antrodia salmonea induces G2 cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athymic nude mice.

    Science.gov (United States)

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Huang, Hui-Chi; Hsu, Li-Sung; Huang, Pei-Jane; Liu, Jer-Yuh; Liao, Jiunn-Wang; Yang, Hsin-Ling

    2017-01-20

    Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. AS (0-200μg/mL) treatment significantly induced G2 cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G2 cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest. Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.

    Science.gov (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Solanki, Sumit; Salotra, Poonam; Nakhasi, Hira L

    2014-06-30

    Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis.

  7. Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Xiao-Mei Wu; Bo Jiang; Chun-Yu Wang; Hai-Nan Zhang; Xiang-Min Shen

    2014-01-01

    Objective:To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34 (GADD34). Methods: A total of 108 healthy male Sprague-Dawley rats were randomly divided into sham operation group, model group and edaravone group (36 cases for each group). Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawley rats. Then, GADD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats. Results: The GADD34 expression was detected in the peri-infarct regions of rats 1 h after reperfusion, which reached its peak 24 h after reperfusion. And edaravone could significantly down-regulate the GADD34 expression. Conclusions:Edaravon could down-regulate GADD34 expression, which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

  8. Influence of edaravone on growth arrest and DNA damage-inducible protein 34 expression following focal cerebral ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Wei; Wang; Xiao-Mei; Wu; Bo; Jiang; Chun-Yu; Wang; Hai-Nan; Zhang; Xiang-Min; Shen

    2014-01-01

    Objective:To investigate the influence of edaravone on the expression of growth arrest and DNA damage-inducible protein 34(GADD34).Methods:A total of 108 healthy male Sprague-Dawlcy rats were randomly divided into sham operation group,model group and edaravone.group(36 cases for each group).Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion in Sprague-Dawlev rats.Then.GAOD34 expression was measured with immunohistochemistry at different time-points after reperfusion in the peri-infarct regions of all rats.Results:The GADD34 expression was detected in the peri-infaret regions of rats 1 h after reperfusion,which reached its peak 24 h after reperfusion.And edaravone could significantly down-regulate the GAOD34 expression.Conclusions:Edaravon could down-regulate GADD34 expression,which suggests that edaravone may exert an important function in inhibiting endoplasmic reticulum stress reaction by scavenging free radicals in the upper stream.

  9. Tempranillo-derived grape seed extract induces apoptotic cell death and cell growth arrest in human promyelocytic leukemia HL-60 cells.

    Science.gov (United States)

    Espino, Javier; González-Gómez, David; Moreno, Daniel; Fernández-León, María F; Rodríguez, Ana B; Pariente, José A; Delgado-Adámez, Jonathan

    2013-12-01

    Although grape seed extract (GSE) has proven to be effective against various cancers, few studies have investigated the effects of GSE on human leukemia. In this study, we analysed the mechanisms involved in the apoptotic effects induced by GSE on human promyelocytic leukemia HL-60 cells. Thus, GSE treatment succeeded in activating caspase-3 (P < 0.05), the activation being dose-dependent and time-dependent. Activation of caspase-3 induced by GSE was accompanied by mitochondrial membrane depolarization (P < 0.05). Moreover, disruption of mitochondrial integrity caused by GSE treatment subsequently led to activation of caspase-9 (P < 0.05), and also produced a slight increase in ROS levels (P < 0.05). Cytotoxic effects elicited by GSE treatment ultimately resulted in extensive S-phase arrest (P < 0.05) and a substantial increase in the intrinsic rate of apoptosis (P < 0.05). Our findings suggest that the GSE induces apoptotic cell death and cell growth inhibition in human leukemic HL-60 cells, which seems to be dependent on mitochondrial damage. Therefore, the GSE obtained from Tempranillo cultivars could be an effective approach to restrain uncontrolled cell proliferation and survival in leukemia cells.

  10. Myeloblastic leukemia cells conditionally blocked by myc-estrogen receptor chimeric transgenes for terminal differentiation coupled to growth arrest and apoptosis.

    Science.gov (United States)

    Selvakumaran, M; Liebermann, D; Hoffman-Liebermann, B

    1993-05-01

    Conditional mutants of the myeloblastic leukemic M1 cell line, expressing the chimeric mycer transgene, have been established. It is shown that M1 mycer cells, like M1, undergo terminal differentiation coupled to growth arrest and programmed cell death (apoptosis) after treatment with the physiologic differentiation inducer interleukin-6. However, when beta-estradiol is included in the culture medium, M1 mycer cells respond to differentiation inducers like M1 myc cell lines, where the differentiation program is blocked at an intermediate stage. By manipulating the function of the mycer transgene product, it is shown that there is a 10-hour window during myeloid differentiation, from 30 to 40 hours after the addition of the differentiation inducer, when the terminal differentiation program switches from being dependent on c-myc suppression to becoming c-myc suppression independent, where activation of c-myc has no apparent effect on mature macrophages. M1 mycer cell lines provide a powerful tool to increase our understanding of the role of c-myc in normal myelopoiesis and in leukemogenesis, also providing a strategy to clone c-myc target genes.

  11. Newt orthologue of Growth arrest-specific 6 (NvGas6) is implicated in stress response during newt forelimb regeneration.

    Science.gov (United States)

    Beug, Shawn; Vascotto, Sandy G; Tsilfidis, Catherine

    2006-03-01

    Red-spotted newts are capable of regenerating various structures and organs through the process of epimorphic regeneration. Receptor tyrosine kinases (RTKs) and their ligands are important for normal cellular development and physiology but most have not yet been characterised during regeneration. We have isolated a newt orthologue of Growth arrest-specific 6 (NvGas6), and examined its expression during forelimb regeneration and within a blastema cell line (B1H1). During limb regeneration, NvGas6 expression increases upon amputation, peaks during maximal blastema cell proliferation, and is subsequently downregulated during redifferentiation. Transcripts are localised to the wound epithelium and distal mesenchymal cells during dedifferentiation and proliferative phases, and scattered within redifferentiating tissues during later stages. In B1H1 cultures, NvGas6 is upregulated under reduced serum conditions and myogenesis. Treatment with mimosine and colchicine or exposure to heat shock or anoxia results in upregulation of NvGas6 expression. Taken together, our findings suggest that during regeneration, NvGas6 expression may be upregulated in response to cellular stress.

  12. Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor

    Directory of Open Access Journals (Sweden)

    Guang-ju Zhao

    2017-01-01

    Full Text Available Background. Growth arrest-specific (Gas 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk, and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.

  13. Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4(+)CD25(+) Regulatory T Cells Mainly through Axl Receptor.

    Science.gov (United States)

    Zhao, Guang-Ju; Zheng, Jia-Yi; Bian, Jia-Lan; Chen, Long-Wang; Dong, Ning; Yu, Yan; Hong, Guang-Liang; Chandoo, Arvine; Yao, Yong-Ming; Lu, Zhong-Qiu

    2017-01-01

    Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4(+)CD25(+)Tregs mainly through its interaction with Axl receptor.

  14. Inhibition of p38-MAPK potentiates cisplatin-induced apoptosis via GSH depletion and increases intracellular drug accumulation in growth-arrested kidney tubular epithelial cells.

    Science.gov (United States)

    Rodríguez-García, Maria Elena; Quiroga, Adoración G; Castro, José; Ortiz, Alberto; Aller, Patricio; Mata, Felicísima

    2009-10-01

    We were interested in analyzing the regulation by mitogen-activated protein kinases (MAPKs) of cisplatin-provoked toxicity in epithelial renal tubule cell lines, when assayed under culture conditions (cell confluence plus serum deprivation), which mimic the characteristics of a nonproliferating epithelium. Under these restrictive growth conditions, cisplatin induced apoptosis with lower efficacy than in exponentially growing cells, and decreased p38-MAPK phosphorylation in NRK-52E and other (LLC-PK1, MDCK, HK2) cell lines. Moreover, cisplatin-provoked apoptosis was potentiated by cotreatment with p38-MAPK-specific inhibitors (SB203580, SB220025) or transfection with a kinase-negative mutant of MKK6, whereas c-Jun NH2-terminal kinase or extracellular signal-regulated kinase/MAPK and ERK Kinase inhibitors were ineffective. By contrast, when applied to exponentially growing cells, cisplatin stimulated p38-MAPK phosphorylation and apoptosis, was attenuated by kinase inhibitors. Treatment of confluent/serum-deprived cells with cisplatin caused mitochondrial transmembrane potential disruption and activated the mitochondrial apoptotic pathway, as indicated by the decrease in Bcl-X(L) expression, increase in Bax expression and cytochrome c release, and these effects were potentiated by cotreatment with SB203580. Treatment of confluent/serum-deprived cells with cisplatin plus SB203580 decreased the intracellular reduced glutathione (GSH) content, and increased intracellular cisplatin accumulation as well as cisplatin binding to DNA. Cotreatment with the GSH-depleting agent D,L-buthionine-R,S-sulfoximine also potentiated cisplatin-provoked apoptosis. In summary, p38-MAPK inhibition potentiates cisplatin-provoked apoptosis in growth-arrested epithelial renal tubule cells, a result that may be explained at least in part by GSH depletion and drug transport alteration.

  15. The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis in Jurkat cells, a model of CD4⁺ T cells.

    Science.gov (United States)

    Wang, Heng; Wang, Yong; Jiang, Xiaoji; Wang, Zhizhong; Zhong, Bing; Fang, Yongfei

    2014-08-01

    CD4(+) T cells in rheumatoid arthritis (RA) express growth signaling pathway in association with deregulated growth and resistance to apoptosis. The janus kinase (Jak) 3 and signal transducer and activator of transcription (STAT) pathway play a critical role in interleukin-2 (IL-2)-induced CD4(+) T cell proliferation. The present study aimed to explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant Rhizoma curcumae. Cell proliferation was determined using WST-1 assay after curcumol treatment. The cell cycle distribution and Bcl-2 protein expression were assessed by flow cytometry. The cellular morphology of apoptosis was evaluated by Hoechst 33258 staining. The expressions of phosphorylated-Jak3 (p-Jak3), p-STAT3, and p-STAT5a following IL-2 stimulation were determined by western blot analysis. The Electrophoretic Mobility Shift Assay was used to detect the DNA binding activities of transcription factors STAT3 and STAT5. The study results showed that curcumol could inhibit the IL-2-induced Jurkat cell proliferation in a concentration- and time-dependent manner in vitro. Curcumol could cause cell cycle arrest at the S phase, induce cell apoptosis, and inhibit the expression of Bcl-2 in a dose-dependent manner. Curcumol at 50μg/mL and Jak3 inhibitor ZM39923 could inhibit the phosphorylation of Jak3 and STAT5a. In conclusion, the underlying mechanism of curcumol on suppressing CD4(+) T cell proliferation and inducing apoptosis might partly be mediated by inhibition of Jak3-STAT5-related molecular activities and Bcl-2 expression, respectively; further studies are required in vivo to test the use of curcumol as a promising therapeutic option for RA.

  16. Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito.

    Science.gov (United States)

    Pastrana-Mena, Rebecca; Dinglasan, Rhoel R; Franke-Fayard, Blandine; Vega-Rodríguez, Joel; Fuentes-Caraballo, Mariela; Baerga-Ortiz, Abel; Coppens, Isabelle; Jacobs-Lorena, Marcelo; Janse, Chris J; Serrano, Adelfa E

    2010-08-27

    Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a gamma-glutamylcysteine synthetase (gamma-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for gamma-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and gamma-GCS by simultaneous disruption of gr and gamma-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism.

  17. Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3beta phosphorylation.

    Science.gov (United States)

    Kumar, Anil; Hou, Xu; Lee, Chunsik; Li, Yang; Maminishkis, Arvydas; Tang, Zhongshu; Zhang, Fan; Langer, Harald F; Arjunan, Pachiappan; Dong, Lijin; Wu, Zhijian; Zhu, Linda Y; Wang, Lianchun; Min, Wang; Colosi, Peter; Chavakis, Triantafyllos; Li, Xuri

    2010-05-14

    Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.

  18. MAC Support for High Density Wireless Sensor Networks

    NARCIS (Netherlands)

    Taddia, C.; Meratnia, Nirvana; van Hoesel, L.F.W.; Mazzini, G.; Havinga, Paul J.M.

    Large scale and high density networks of tiny sensor nodes offer promising solutions for event detection and actuating applications. In this paper we address the effect of high density of wireless sensor network performance with a specific MAC protocol, the Lightweight Medium Access Control (LMAC).

  19. Inositol Hexaphosphate Inhibits Growth and Induces G1 Arrest and Apoptotic Death of Androgen-Dependent Human Prostate Carcinoma LNCaP Cells1

    Science.gov (United States)

    Agarwal, Chapla; Dhanalakshmi, Sivanandhan; Singh, Rana P; Agarwal, Rajesh

    2004-01-01

    Abstract Prostate cancer (PCA) is the most common invasive malignancy and the second leading cause of cancer-related deaths in the US male population. One approach to control this malignancy is its preventive intervention by dietary agents. Inositol hexaphosphate (IP6), a dietary constituent, has shown promising efficacy against various cancers; however, limited studies have been performed with IP6 against PCA. Here, we investigated the growth-inhibitory effect and associated mechanisms of IP6 in androgen-dependent human prostate carcinoma LNCaP cells. IP6 treatment of cells resulted in a strong growth inhibition and an increase in G1 cell population. In mechanistic studies, IP6 resulted in an increase in cyclin-dependent kinase inhibitors (CDKIs) Cip1/p21 and Kip1/p27 levels, together with a decrease in cyclin-dependent kinase (CDK) 4 and cyclin D1 protein levels. An increase in CDKI levels by IP6 also led to a concomitant increase in their interactions with CDK2 and CDK4, together with a strong decrease in the kinase activity of both CDKs. Downstream in CDKI-CDK-cyclin cascade, consistent with its inhibitory effect on CDK kinase activity, IP6 treatment of cells increased hypophosphorylated levels of retinoblastoma (Rb) with a decrease in Rb phosphorylation at serine 780, 807, and 811 sites, and caused a moderate to strong decrease in the levels of transcription factors E2F1, E2F4, and E2F5. In other studies, IP6 caused a dose- and a time-dependent apoptotic death of LNCaP cells, and a decrease in Bcl2 levels, causing a strong increase in Bax versus Bcl2 ratio, as well as an inhibition of constitutively active AKT phosphorylation. Taken together, these molecular alterations provide an insight into IP6-caused growth inhibition, G1 arrest, and apoptotic death of human prostate carcinoma LNCaP cells. Because early clinical PCA growth is an androgen-dependent response, the results of the present study employing androgen-dependent LNCaP cells suggest that IP6 has

  20. Inositol Hexaphosphate Inhibits Growth and Induces G1 Arrest and Apoptotic Death of Androgen-Dependent Human Prostate Carcinoma LNCaP Cells

    Directory of Open Access Journals (Sweden)

    Chapla Agarwal

    2004-09-01

    Full Text Available Prostate cancer (PCA is the most common invasive malignancy and the second leading cause of cancerrelated deaths in the US male population. One approach to control this malignancy is its preventive intervention by dietary agents. Inositol hexaphosphate (IP6, a dietary constituent, has shown promising efficacy against various cancers; however, limited studies have been performed with IP6 against PCA. Here, we investigated the growth-inhibitory effect and associated mechanisms of IP6 in androgen-dependent human prostate carcinoma LNCaP cells. IP6 treatment of cells resulted in a strong growth inhibition and an increase in G1 cell population. In mechanistic studies, IP6 resulted in an increase in cyclin-dependent kinase inhibitors (CDKIs Cipi/p21 and Kip1/p27 levels, together with a decrease in cyclin-dependent kinase (CDK 4 and cyclin D1 protein levels. An increase in CDKI levels by IP6 also led to a concomitant increase in their interactions with CDK2 and CDK4, together with a strong decrease in the kinase activity of both CDKs. Downstream in CDKI-CDK-cyclin cascade, consistent with its inhibitory effect on CDK kinase activity, IP6 treatment of cells increased hypophosphorylated levels of retinoblastoma (Rb with a decrease in Rb phosphorylation at serine 780, 807, and 811 sites, and caused a moderate to strong decrease in the levels of transcription factors E2F1, E2F4, and E2F5. In other studies, IP6 caused a dose- and a time-dependent apoptotic death of LNCaP cells, and a decrease in Bcl2 levels, causing a strong increase in Bax versus Bcl2 ratio, as well as an inhibition of constitutively active AKT phosphorylation. Taken together, these molecular alterations provide an insight into IP6-caused growth inhibition, G1 arrest, and apoptotic death of human prostate carcinoma LNCaP cells. Because early clinical PCA growth is an androgen-dependent response, the results of the present study employing androgendependent LNCaP cells suggest that IP6 has

  1. Physeal arrest of the distal radius.

    Science.gov (United States)

    Abzug, Joshua M; Little, Kevin; Kozin, Scott H

    2014-06-01

    Fractures of the distal radius are among the most common pediatric fractures. Although most of these fractures heal without complication, some result in partial or complete physeal arrest. The risk of physeal arrest can be reduced by avoiding known risk factors during fracture management, including multiple attempts at fracture reduction. Athletes may place substantial compressive and shear forces across the distal radial physes, making them prone to growth arrest. Timely recognition of physeal arrest can allow for more predictable procedures to be performed, such as distal ulnar epiphysiodesis. In cases of partial arrest, physeal bar excision with interposition grafting can be performed. Once ulnar abutment is present, more invasive procedures may be required, including ulnar shortening osteotomy or radial lengthening.

  2. Growth Arrest-Specific 6 Protein in Patients with Sjogren Syndrome: Determination of the Plasma Level and Expression in the Labial Salivary Gland.

    Directory of Open Access Journals (Sweden)

    Chen-Hung Chen

    Full Text Available Growth arrest-specific protein 6 (Gas6 is a vitamin K-dependent protein expressed by endothelial cells and leukocytes that are involved in cell survival, migration, and proliferation in response to inflammatory processes. The aim of this study was to assess the implications of Gas6 in Sjögren syndrome (SS and its expression in the labial salivary gland.A total of 254 adults, including 159 with primary Sjögren syndrome (pSS, 34 with secondary Sjögren syndrome (sSS, and 61 normal controls, were recruited. Plasma Gas6 concentrations were determined, and Gas6 expressions in labial salivary gland (LSG tissues from controls and pSS and sSS patients were also evaluated. Plasma Gas6 concentrations were significantly lower among patients with pSS than normal controls (13.5 ± 8.6 vs. 19.9 ± 13.4 ng/ml, p < 0.001. There were, however, no significant differences in plasma Gas6 levels between pSS and sSS patients (13.5 ± 8.6 vs. 16.9 ± 11.2 ng/ml, p = 0.068. In multivariate logistic regression analysis, after adjustment for white blood cell count, hemoglobin level, platelet count, lymphocyte count, and C3 and C4 levels, lower plasma Gas6 concentrations were significantly associated with an increased risk of SS. Moreover, by using a semi-quantitative scale to evaluate Gas6 expression in LSG tissues, Gas6 expression was found to be markedly lower in LSG tissues from pSS patients than in tissues from normal controls.Decreased plasma Gas6 concentration and LSG expression were associated with pSS. As such, Gas6 may represent a novel independent risk factor for pSS, with a potential role in salivary gland inflammation and dysfunction.

  3. Hwanggeumchal sorghum Induces Cell Cycle Arrest, and Suppresses Tumor Growth and Metastasis through Jak2/STAT Pathways in Breast Cancer Xenografts

    Science.gov (United States)

    Lim, Eun Joung; Joung, Youn Hee; Hong, Dae Young; Park, Eui U.; Park, Seung Hwa; Choi, Soo Keun; Moon, Eon-Soo; Cho, Byung Wook; Park, Kyung Do; Lee, Hak Kyo; Kim, Myong-Jo; Park, Dong-Sik; Yang, Young Mok

    2012-01-01

    Background Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer. Methodology/Principal Findings Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model. Conclusions/Significance Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer. PMID:22792362

  4. Suppression of growth arrest and DNA damage-inducible 45alpha expression confers resistance to sulindac and indomethacin-induced gastric mucosal injury.

    Science.gov (United States)

    Chiou, Shiun-Kwei; Hodges, Amy; Hoa, Neil

    2010-09-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin are a major cause of gastric erosions and ulcers. Induction of apoptosis by NSAIDs is an important mechanism involved. Understanding how NSAIDs affect genes that regulate apoptosis is useful for designing therapeutic or preventive strategies and for evaluating the efficacy of safer drugs being developed. We investigated whether growth arrest and DNA damage-inducible 45alpha (GADD45alpha), a stress signal response gene involved in regulation of DNA repair and induction of apoptosis, plays a part in NSAID-induced gastric mucosal injury and apoptosis in vivo in mice and in vitro in cultured human AGS and rat RGM-1 gastric epithelial cells. Intraperitoneal administration of sulindac and indomethacin both resulted in up-regulation of GADD45alpha expression and induction of significant injury and apoptosis in gastric mucosa of wild-type mice. GADD45alpha(-/-) mice were markedly more resistant to both sulindac- and indomethacin-induced gastric mucosal injury and apoptosis than wild-type mice. Sulindac sulfide and indomethacin treatments also concentration-dependently increased GADD45alpha expression and apoptosis in AGS and RGM-1 cells. Antisense suppression of GADD45alpha expression significantly reduced sulindac and indomethacin-induced activation of caspase-9 and apoptosis in AGS cells. Pretreatments with exogenous prostaglandins and small interfering RNA suppression of cyclooxygenase (COX)-1 and -2 did not affect up-regulation of GADD45alpha by sulindac sulfide and indomethacin in AGS cells. These findings indicate that GADD45alpha up-regulation is a COX-independent mechanism that is required for induction of severe gastric mucosal apoptosis and injury by NSAIDs, probably via a capase-9-dependent pathway of programmed cell death.

  5. Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jonathan Krell

    Full Text Available The growth arrest-specific transcript 5 gene (GAS5 encodes a long noncoding RNA (lncRNA and hosts a number of small nucleolar RNAs (snoRNAs that have recently been implicated in multiple cellular processes and cancer. Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the potential role of this locus in cell survival and oncogenesis both in vivo and in vitro.We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response.GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA expression in colorectal tissue.In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have an important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome. We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used as endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments can lead to inaccurate results.

  6. Inhibition of activated receptor tyrosine kinases by Sunitinib induces growth arrest and sensitizes melanoma cells to Bortezomib by blocking Akt pathway.

    Science.gov (United States)

    Yeramian, Andree; Sorolla, Anabel; Velasco, Ana; Santacana, Maria; Dolcet, Xavier; Valls, Joan; Abal, Leandre; Moreno, Sara; Egido, Ramón; Casanova, Josep M; Puig, Susana; Vilella, Ramón; Llombart-Cussac, Antonio; Matias-Guiu, Xavier; Martí, Rosa M

    2012-02-15

    Despite the use of multiple therapeutic strategies, metastatic melanoma remains a challenge for oncologists. Thus, new approaches using combinational treatment may be used to try to improve the prognosis of this disease. In this report, we have analyzed the expression of receptor tyrosine kinases (RTKs) in melanoma specimens and in four metastatic melanoma cell lines. Both melanoma specimens and cell lines expressed RTKs, suggesting that they may represent eventual targets for multitargeted tyrosine kinase inhibitor, Suntinib. Sunitinib reduced the proliferation of two melanoma cell lines (M16 and M17) and increased apoptosis in one of them (M16). Moreover, the two metastatic melanoma cell lines harbored an activated receptor (PDGFRα and VEGFR, respectively), and Sunitinib suppressed the phosphorylation of the RTKs and their downstream targets Akt and ribosomal protein S6, in these two cell lines. Similar results were obtained when either PDGFRα or VEGFR2 expression was silenced by lentiviral-mediated short-hairpin RNA delivery in M16 and M17, respectively. To evaluate the interaction between Sunitinib and Bortezomib, median dose effect analysis using MTT assay was performed, and combination index was calculated. Bortezomib synergistically enhanced the Sunitinib-induced growth arrest in Sunitinib-sensitive cells (combination index < 1). Moreover, LY294002, a PI3K inhibitor, sensitized melanoma cells to Bortezomib treatment, suggesting that downregulation of phospho-Akt by Sunitinib mediates the synergy obtained by Bortezomib + Sunitinib cotreatment. Altogether, our results suggest that melanoma cells harboring an activated RTK may be clinically responsive to pharmacologic RTK inhibition by Sunitinib, and a strategy combining Sunitinib and Bortezomib, may provide therapeutic benefit. Copyright © 2011 UICC.

  7. Hwanggeumchal sorghum induces cell cycle arrest, and suppresses tumor growth and metastasis through Jak2/STAT pathways in breast cancer xenografts.

    Directory of Open Access Journals (Sweden)

    Jin Hee Park

    Full Text Available BACKGROUND: Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model. CONCLUSIONS/SIGNIFICANCE: Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer.

  8. Continuous planting under a high density enhances the competition for nutrients among young Cunninghamia lanceolata saplings

    OpenAIRE

    Dong, Tingfa; Zhang, Yunxiang; Zhang,Yuanbin; Zhang, Sheng

    2016-01-01

    International audience; AbstractKey messageA high-density plantation inhibited growth and biomass accumulation of Cunninghamia lanceolata(Lamb.) Hook. saplings, as well as their photosynthesis. This inhibition was enhanced in a soil that had been previously planted with the same species. The main factors limiting photosynthesis and growth were leaf-level irradiance and nutrient availability, mainly of P and Mg.ContextThe planting density and continuous planting greatly affect the photosynthes...

  9. N-Methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA

    Directory of Open Access Journals (Sweden)

    Narayan Satya

    2004-01-01

    Full Text Available Abstract Background Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG is able to induce senescence in the HCT-116 colon cancer cell line. Results Cells treated with lower concentrations of MNNG (0–25 microM for 50 h showed a dose-dependent increase in G2/M phase arrest and apoptosis; however, cells treated with higher concentrations of MNNG (50–100 microM showed a senescence-like G0/G1 phase arrest which was confirmed by increased expression of β-galactosidase, a senescence induced marker. The G2/M phase arrest and apoptosis were found to be associated with increased levels of p53 protein, but the senescence-like G0/G1 phase arrest was dissociated with p53 protein levels, since the p53 protein levels decreased in senescence-like arrested cells. We further, determined whether the decreased level of p53 was a transcriptional or a translational phenomenon. The results revealed that the decreased level of p53 protein in senescence-like arrested cells was a transcriptional phenomenon since p53 mRNA levels simultaneously decreased after treatment with higher concentrations of MNNG. We also examined the effect of MNNG treatment on other cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The expression levels of these proteins were increased in cells treated with lower concentrations of MNNG, which supported the G2/M phase arrest. However, cells treated with higher concentrations of MNNG showed decreased levels of these proteins, and hence, may not play a role in cell cycle arrest. We then examined a possible association of the expression of APC protein and telomeric DNA signals with cellular senescence in MNNG-treated cells. We found that protein and m

  10. The effect of water stress on super-high- density 'Koroneiki' olive oil quality.

    Science.gov (United States)

    Dag, Arnon; Naor, Amos; Ben-Gal, Alon; Harlev, Guy; Zipori, Isaac; Schneider, Doron; Birger, Reuven; Peres, Moti; Gal, Yoni; Kerem, Zohar

    2015-08-15

    Over the last two decades, the area of cultivated super-high-density olive orchards has increased rapidly. Water stress is an important tool in super-high-density orchards to reduce tree growth and promote suitability for overhead mechanical harvesters. Little is known regarding the effect of water stress in super-high-density orchards on oil quality parameters. In this study the effect of irrigation rate on oil quality parameters was evaluated in a six-year-old super-high-density 'Koreneiki' olive orchard for five consecutive seasons. Five water status levels, determined by irrigating in order to maintain various midday stem water potential threshold values (-1.5, -2, -2.5, -3 and -4 MPa), were applied during the oil accumulation stage. The MUFA/PUFA ratio and free fatty acid content generally decreased as a function of increasing tree water stress. In most seasons a reduction in polyphenols was found with decreasing irrigation level. Peroxide value was not affected by the water stress level. The present study demonstrates that limiting irrigation and exposure of olive trees to water stress in a super-high-density orchard lowers free fatty acid content and therefore benefits oil quality. However, the decreased MUFA/PUFA ratio and the reduction in polyphenol content that were also found under increased water stress negatively influence oil quality. © 2014 Society of Chemical Industry.

  11. 128x128 Ultra-High Density Optical Interconnect Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Future NASA programs like Tertiary Planet Finder (TPF) require high-density deformable mirrors with up to 16,000 actuators to enable direct imaging of planets around...

  12. 128x128 Ultra-High Density Optical Interconnect Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Future NASA programs like Tertiary Planet Finder (TPF) require high density deformable mirrors with upto 16,000 actuators to enable direct imaging of planets around...

  13. Application of a high density adsorbent in expanded bed adsorption ...

    African Journals Online (AJOL)

    PRECIOUS

    2010-01-11

    Jan 11, 2010 ... The high density of the adsorbent allowed the EBA to be operated at linear velocity as high as 657 cm/h ... through precipitation and even dialyzed before sample ... In EBA process, upward fluidized stationary phase with.

  14. The usefulness of total cholesterol and high density lipoprotein ...

    African Journals Online (AJOL)

    The usefulness of total cholesterol and high density lipoprotein - cholesterol ratio in ... cholesterol and/or highdensity lipoprotein cholesterol/total cholesterol ratios in the interpretation of lipid profile result in clinical practice. ... Article Metrics.

  15. Observable to explore high density behaviour of symmetry energy

    CERN Document Server

    Sood, Aman D

    2011-01-01

    We aim to see the sensitivity of collective transverse in-plane flow to symmetry energy at low as well as high densities and also to see the effect of different density dependencies of symmetry energy on the same.

  16. High regression rate, high density hybrid fuels Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR program will investigate high energy density novel nanofuels combined with high density binders for use with an N2O oxidizer. Terves has developed...

  17. Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches

    National Research Council Canada - National Science Library

    deGoma, Emil M; deGoma, Rolando L; Rader, Daniel J

    2008-01-01

    A number of therapeutic strategies targeting high-density lipoprotein (HDL) cholesterol and reverse cholesterol transport are being developed to halt the progression of atherosclerosis or even induce regression...

  18. Structural arrest in an ideal gas.

    Science.gov (United States)

    van Ketel, Willem; Das, Chinmay; Frenkel, Daan

    2005-04-08

    We report a molecular dynamics study of a simple model system that has the static properties of an ideal gas, yet exhibits nontrivial "glassy" dynamics behavior at high densities. The constituent molecules of this system are constructs of three infinitely thin hard rods of length L, rigidly joined at their midpoints. The crosses have random but fixed orientation. The static properties of this system are those of an ideal gas, and its collision frequency can be computed analytically. For number densities NL(3)/V>1, the single-particle diffusivity goes to zero. As the system is completely structureless, standard mode-coupling theory cannot describe the observed structural arrest. Nevertheless, the system exhibits many dynamical features that appear to be mode-coupling-like. All high-density incoherent intermediate scattering functions collapse onto master curves that depend only on the wave vector.

  19. Effect of Common Genetic Variants of Growth Arrest-Specific 6 Gene on Insulin Resistance, Obesity and Type 2 Diabetes in an Asian Population.

    Directory of Open Access Journals (Sweden)

    Chang-Hsun Hsieh

    Full Text Available Growth arrest-specific 6 (Gas6, a vitamin K-dependent protein, has been implicated in systemic inflammation, obesity, and insulin resistance (IR. Data from recent studies suggest that polymorphisms in the Gas6 gene are associated with cardiovascular disorders and type 2 diabetes (T2D. However, the association of Gas6 gene variants with obesity, IR, and T2D development has not been explored.Four common single nucleotide polymorphisms (SNPs in the Gas6 gene were genotyped in 984 participants from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe family cohort. An insulin suppression test was performed to determine IR based on steady-state plasma glucose (SSPG. Associations between IR indices and obesity, and SNP genotypes, based on previously-reported data for this cohort (Phase I, were analyzed. In the present follow-up study (Phase II, the effects of gene variants of Gas6 on the progression to T2D were explored in individuals who were free of T2D in Phase I. The mean follow-up period for Phase II was 5.7 years.The mean age of the study population in Phase I was 49.5 years and 16.7% of individuals developed T2D during follow-up. After adjusting for covariates, three SNPs (rs8191973, rs8197974, and rs7323932 were found to be associated with SSPG levels (p = 0.007, p = 0.03, and p = 0.011, respectively. This association remained significant after multiple testing and showed a significant interaction with physical activity for SNP rs8191973. However, no other significant correlations were observed between Gas6 polymorphisms and other indices of IR or obesity. A specific haplotype, AACG (from rs8191974, rs7323932, rs7331124, and rs8191973, was positively associated with SSPG levels (p = 0.0098. None of the polymorphisms were associated with an increased risk of T2D development.Our results suggest that Gas6 gene variants are associated with IR, although their effects on subsequent progression to T2D were minimal in

  20. Salter-Harris Type III and IV medial malleolar fractures: growth arrest: is it a fate? A retrospective study of 48 cases with open reduction.

    Science.gov (United States)

    Cottalorda, Jérôme; Béranger, Vincent; Louahem, Djamel; Camilleri, Jean Philippe; Launay, Franck; Diméglio, Alain; Bourelle, Sophie; Jouve, Jean-Luc; Bollini, Gérard

    2008-09-01

    Salter-Harris type III and IV medial malleolar fractures (MacFarland fracture) is a joint fracture of the ankle in children. The fracture line passes through the medial part of the lower epiphyseal disk of the tibia. Prognosis is dominated by later risk of misalignment and osteoarthritis. The aim of this study was to evaluate the functional and radiological outcome of these fractures. We retrospectively analyzed the cases of 48 children with MacFarland fractures (31 boys and 17 girls), mean age at the time of trauma 11 years 6 months (range, 8-15 years). The fractures were classed into two groups according to the Salter and Harris classification for epiphyseal detachment: Salter III (30 cases) and Salter IV (18 cases). Surgical treatment was given in all cases (46 screw fixations, 2 pin fixations). Three outcome categories were used: good (no pain, no stiffness, no limp, no misalignment, no surgical complication, no healing problem), fair (pain and/or stiffness and/or limp and/or healing problem without misalignment, no surgical complication), and poor (misalignment or surgical complication). Mean follow-up was 3 years and 3 months (24-94 months). Twenty-eight children were skeletally mature at the longest follow-up. The three-month postoperative assessment showed 35 patients with good results and 13 children with fair results. Ankle stiffness was noted in 6 cases, ankle pain in 4 cases, wound healing complications in 4 cases, limp in 1 case, and snapping in 1 case. The long-term outcome was considered good for 45 patients, fair for 2 patients (1 wound adherence and 1 hypertrophic scar tissue), and poor for 1 patient (6-degree varus deformity). We did not note leg-length discrepancy or malunion at the longest follow-up. Our results show that growth arrest after MacFarland fracture is no fate. We used surgery more than is generally reported by other teams, opting for surgery as soon as the displacement was >or=1 mm. Surgical treatment was arthrotomy in all cases to

  1. Transforming growth factor-β1 induces cell cycle arrest by activating atypical cyclin-dependent kinase 5 through up-regulation of Smad3-dependent p35 expression in human MCF10A mammary epithelial cells.

    Science.gov (United States)

    Park, Seong Ji; Yang, Sun Woo; Kim, Byung-Chul

    2016-04-01

    Cyclin-dependent kinases (Cdks) play important roles in control of cell division. Cdk5 is an atypical member of Cdk family with non-cyclin-like regulatory subunit, p35, but its role in cell cycle progression is still unclear. In the present study, we investigated the role of Cdk5/p35 on transforming growth factor-β1 (TGF-β1)-induced cell cycle arrest. In human MCF10A mammary epithelial cells, TGF-β1 induced cell cycle arrest at G1 phase and increased p27KIP1 expression. Interestingly, pretreatment with roscovitine, an inhibitor of Cdk5, or transfection with small interfering (si) RNAs specific to Cdk5 and p35 significantly attenuated the TGF-β1-induced p27KIP1 expression and cell cycle arrest. TGF-β1 increased Cdk5 activity via up-regulation of p35 gene at transcriptional level, and these effects were abolished by transfection with Smad3 siRNA or infection of adenovirus carrying Smad3 mutant at the C-tail (3SA). Chromatin immunoprecipitation assay further revealed that wild type Smad3, but not mutant Smad3 (3SA), binds to the region of the p35 promoter region (-1000--755) in a TGF-β1-dependent manner. These results for the first time demonstrate a role of Cdk5/p35 in the regulation of cell cycle progression modulated by TGF-β1.

  2. High-density scintillating glasses for a proton imaging detector

    Science.gov (United States)

    Tillman, I. J.; Dettmann, M. A.; Herrig, V.; Thune, Z. L.; Zieser, A. J.; Michalek, S. F.; Been, M. O.; Martinez-Szewczyk, M. M.; Koster, H. J.; Wilkinson, C. J.; Kielty, M. W.; Jacobsohn, L. G.; Akgun, U.

    2017-06-01

    High-density scintillating glasses are proposed for a novel proton-imaging device that can improve the accuracy of the hadron therapy. High-density scintillating glasses are needed to build a cost effective, compact calorimeter that can be attached to a gantry. This report summarizes the study on Europium, Terbium, and Cerium-doped scintillating glasses that were developed containing heavy elements such as Lanthanum, Gadolinium, and Tungsten. The density of the samples reach up to 5.9 g/cm3, and their 300-600 nm emission overlaps perfectly with the peak cathode sensitivity of the commercial photo detectors. The developed glasses do not require any special quenching and can be poured easily, which makes them a good candidate for production in various geometries. Here, the glass making conditions, preliminary tests on optical and physical properties of these scintillating, high-density, oxide glasses developed for a novel medical imaging application are reported.

  3. Growth-arrest-specific 7C protein inhibits tumor metastasis via the N-WASP/FAK/F-actin and hnRNP U/β-TrCP/β-catenin pathways in lung cancer

    OpenAIRE

    Tseng, Ruo-Chia; Chang, Jer-Wei; Mao, Jiou-Shan; Tsai, Charng-Dar; Wu, Pei-Chen; Lin, Cuei-Jyuan; Lu, Yi-Lin; Liao, Sheng-You; Cheng, Hung-Chi; Hsu, Han-Shui; Wang, Yi-Ching

    2015-01-01

    Growth-arrest-specific 7 (GAS7) belongs to a group of adaptor proteins that coordinate the actin cytoskeleton. Among human GAS7 isoforms, only GAS7C possesses a Src homology 3 domain. We report here that GAS7C acts as a migration suppressor and can serve as a prognostic biomarker in lung cancer. GAS7C overexpression reduces lung cancer migration, whereas GAS7C knockdown enhances cancer cell migration. Importantly, ectopically overexpressed GAS7C binds tightly with N-WASP thus inactivates the ...

  4. Combination of Low Concentration of (−-Epigallocatechin Gallate (EGCG and Curcumin Strongly Suppresses the Growth of Non-Small Cell Lung Cancer in Vitro and in Vivo through Causing Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Wenbin Huang

    2013-06-01

    Full Text Available (−-Epigallocatechin gallate (EGCG and curcumin are two naturally derived agents that have been widely investigated worldwide. They exhibit their anti-tumor effects in many types of cancers. In the current study, the effect of the combination of the two agents on non-small cell lung cancer (NSCLC cells was investigated. The results revealed that at low concentrations, the combination of the EGCG and curcumin strongly enhanced cell cycle arrest. Flow cytometry analysis showed that the cells were arrested at G1 and S/G2 phases. Two main cell cycle related proteins cyclin D1 and cyclin B1 were significantly inhibited at the present of EGCG and curcumin. EdU (5-ethynyl-2'-deoxyuridine fluorescence staining showed that the DNA replication was significantly blocked. A clonal growth assay also confirmed a marked repression of cell growth. In a lung cancer xenograft node mice model, combination of EGCG and curcumin exhibited protective effect against weight loss due to tumor burden. Tumor growth was strongly repressed by the combination of the two agents, without causing any serious side-effect. Overall, these results strongly suggest that EGCG in combination with curcumin could be a candidate for chemoprevention agent of NSCLC.

  5. Intraocular inflammation following endotamponade with high-density silicone oil.

    NARCIS (Netherlands)

    Theelen, T.; Tilanus, M.A.D.; Klevering, B.J.

    2004-01-01

    BACKGROUND: The use of a mixture of silicone oil and partially fluorinated alkanes (high-density silicone oil) has recently been suggested as intraocular tamponade in complicated retinal detachment of the inferior quadrants. We describe a series of patients who developed a clinical picture resemblin

  6. Sputtered thin films for high density tape recording

    NARCIS (Netherlands)

    Nguyen, L.T.

    This thesis describes the investigation of sputtered thin film media for high density tape recording. As discussed in Chapter 1, to meet the tremendous demand of data storage, the density of recording tape has to be increased continuously. For further increasing the bit density the key factors are:

  7. Sputtered thin films for high density tape recording

    NARCIS (Netherlands)

    Nguyen, L.T.

    2004-01-01

    This thesis describes the investigation of sputtered thin film media for high density tape recording. As discussed in Chapter 1, to meet the tremendous demand of data storage, the density of recording tape has to be increased continuously. For further increasing the bit density the key factors are:

  8. Two-Dimensional Super High Density Multi-Fiber Connector

    Institute of Scientific and Technical Information of China (English)

    Takashi Shigenaga; Katsuki Suematsu; Masao Shinoda; Takayuki Ando

    2003-01-01

    We have developed 32-fiber and 60-fiber super high density multi fiber connector. This 32-fiber connector can be applicable for single-mode fiber and 60-fiber connector for multi-mode fiber. We have also established PC (physical contact) connection technology by optimizing polishing condition and clamping force.

  9. Mendelian Disorders of High-Density Lipoprotein Metabolism

    NARCIS (Netherlands)

    Oldoni, Federico; Sinke, Richard J.; Kuivenhoven, Jan Albert

    2014-01-01

    High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL chol

  10. Interaction effects in high density magnetic particulate media

    Energy Technology Data Exchange (ETDEWEB)

    Cerchez, Mihai; Stoleriu, Laurentiu; Stancu, Alexandru

    2004-01-01

    The paper presents a micromagnetic study of the particulate high density recording media. The main difference in the behavior of such a system is the appearance of magnetic clusters which lead to a different behavior of the system. New hypotheses for interpreting such systems are presented.

  11. Metabolism of high density lipoproteins in liver cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Ning Xu; Chang-Ping Wu

    2007-01-01

    Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.

  12. Intraocular inflammation following endotamponade with high-density silicone oil.

    NARCIS (Netherlands)

    Theelen, T.; Tilanus, M.A.D.; Klevering, B.J.

    2004-01-01

    BACKGROUND: The use of a mixture of silicone oil and partially fluorinated alkanes (high-density silicone oil) has recently been suggested as intraocular tamponade in complicated retinal detachment of the inferior quadrants. We describe a series of patients who developed a clinical picture

  13. A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

    Directory of Open Access Journals (Sweden)

    Scott J Cameron

    Full Text Available High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC. Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis.

  14. High-density turbidity currents: Are they sandy debris flows?

    Energy Technology Data Exchange (ETDEWEB)

    Shanmugam, G. [Mobil Exploration and Producing Technical Center, Dallas, TX (United States)

    1996-01-01

    Conventionally, turbidity currents are considered as fluidal flows in which sediment is supported by fluid turbulence, whereas debris flows are plastic flows in which sediment is supported by matrix strength, dispersive pressure, and buoyant lift. The concept of high-density turbidity current refers to high-concentration, commonly non-turbulent, flows of fluids in which sediment is supported mainly by matrix strength, dispersive pressure, and buoyant lift. The conventional wisdom that traction carpets with entrained turbulent clouds on top represent high-density turbidity currents is a misnomer because traction carpets are neither fluidal nor turbulent. Debris flows may also have entrained turbulent clouds on top. The traction carpet/debris flow and the overriding turbulent clouds are two separate entities in terms of flow rheology and sediment-support mechanism. In experimental and theoretical studies, which has linked massive sands and floating clasts to high-density turbidity currents, the term high-density turbidity current has actually been used for laminar flows. In alleviating this conceptual problem, sandy debris flow is suggested as a substitute for high-density turbidity current. Sandy debris flows represent a continuous spectrum of processes between cohesive and cohesionless debris flows. Commonly they are rheologically plastic. They may occur with or without entrained turbulent clouds on top. Their sediment-support mechanisms include matrix strength, dispersive pressure, and buoyant lift. They are characterized by laminar flow conditions, a moderate to high grain concentration, and a low to moderate mud content. Although flows evolve and transform during the course of transport in density-stratified flows, the preserved features in a deposit are useful to decipher only the final stages of deposition. At present, there are no established criteria to decipher transport mechanism from the depositional record.

  15. 高密度养殖下革胡子鲶生长激素mRNA表达的半定量分析%Semi-quantitative Analysis of Growth Hormone(GH) mRNA Expression of Clarias gariepinus in High Density Pond Culture

    Institute of Scientific and Technical Information of China (English)

    王晓梅; 戴伟; 郭永军; 陈承勋; 李娜; 张茂群

    2011-01-01

    以β-肌动蛋白(β-actin)mRNA的表达量作为内标,应用半定量RT-PCR法,对高密度养殖条件下不同月龄革胡子鲶垂体生长激素(Growth hormone,GH)mRNA的相对表达量进行分析.结果显示:3.5,5,6.5月龄试验鱼的GH mRNA的相对表达量分别为3.612~5.965,2.929~4.556和1.360~1.821;平均相对表达量分别为4.346±0.656 0,3.649±0.568 4和1.575±0.135 5.上述数据经方差分析得出,革胡子鲶任意两个不同月龄之间GH mRNA相对表达量的差异达到1%的显著水平.Duncan氏多重比较结果显示,3.5,5月龄试验鱼垂体GH mRNA的平均相对表达量差异不显著,但均极显著高于6.5月龄.%Using β-actin mRNA expression quantity as an internal reference,the differences of growth hormone (GH) mRNA expression in pituitary of Clarias gariepinus in high density pond culture at different months old were analyzed with the employment of semi-quantitative RT-PCR method. The relative expression quantity of GH mRNA of individuals at 3.5,5 and 6.5 months old were 3. 612 - 5. 965,2. 929 - 4. 556 and 1. 360 - 1. 821 ,respectively, while the mean relative expressions were 4.346 ±0.656 0,3. 649 ±0.568 4 and 1. 575 ± 0. 135 5 separately for 3.5,5 and 6.5 months old. The variance analysis indicated that the significant differences reached 1% in the relative expression level of the GH mRNA between any two months old. The Duncan's multiple comparison showed that the differences of GH mRNA expression between that at 3.5 and 6.5 months old as well as that at 5 and 6.5 months old were extremely significant,but there was no difference of GH mRNA expression between that at 3.5 and 5 months old.

  16. Cardiac arrest in children

    Directory of Open Access Journals (Sweden)

    Tress Erika

    2010-01-01

    Full Text Available Major advances in the field of pediatric cardiac arrest (CA were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners.

  17. Pittsburgh Police Arrest Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Arrest data contains information on people taken into custody by City of Pittsburgh police officers. More serious crimes such as felony offenses are more likely to...

  18. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  19. High-density carbon ablator ignition path with low-density gas-filled rugby hohlraum

    Science.gov (United States)

    Amendt, Peter; Ho, Darwin D.; Jones, Ogden S.

    2015-04-01

    A recent low gas-fill density (0.6 mg/cc 4He) cylindrical hohlraum experiment on the National Ignition Facility has shown high laser-coupling efficiency (>96%), reduced phenomenological laser drive corrections, and improved high-density carbon capsule implosion symmetry [Jones et al., Bull. Am. Phys. Soc. 59(15), 66 (2014)]. In this Letter, an ignition design using a large rugby-shaped hohlraum [Amendt et al., Phys. Plasmas 21, 112703 (2014)] for high energetics efficiency and symmetry control with the same low gas-fill density (0.6 mg/cc 4He) is developed as a potentially robust platform for demonstrating thermonuclear burn. The companion high-density carbon capsule for this hohlraum design is driven by an adiabat-shaped [Betti et al., Phys. Plasmas 9, 2277 (2002)] 4-shock drive profile for robust high gain (>10) 1-D ignition performance and large margin to 2-D perturbation growth.

  20. High-density carbon ablator ignition path with low-density gas-filled rugby hohlraum

    Energy Technology Data Exchange (ETDEWEB)

    Amendt, Peter; Ho, Darwin D.; Jones, Ogden S. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States)

    2015-04-15

    A recent low gas-fill density (0.6 mg/cc {sup 4}He) cylindrical hohlraum experiment on the National Ignition Facility has shown high laser-coupling efficiency (>96%), reduced phenomenological laser drive corrections, and improved high-density carbon capsule implosion symmetry [Jones et al., Bull. Am. Phys. Soc. 59(15), 66 (2014)]. In this Letter, an ignition design using a large rugby-shaped hohlraum [Amendt et al., Phys. Plasmas 21, 112703 (2014)] for high energetics efficiency and symmetry control with the same low gas-fill density (0.6 mg/cc {sup 4}He) is developed as a potentially robust platform for demonstrating thermonuclear burn. The companion high-density carbon capsule for this hohlraum design is driven by an adiabat-shaped [Betti et al., Phys. Plasmas 9, 2277 (2002)] 4-shock drive profile for robust high gain (>10) 1-D ignition performance and large margin to 2-D perturbation growth.

  1. Noise reduction in muon tomography for detecting high density objects

    CERN Document Server

    Benettoni, M; Bonomi, G; Calvagno, G; Calvini, P; Checchia, P; Cortelazzo, G; Cossutta, L; Donzella, A; Furlan, M; Gonella, F; Pegoraro, M; Garola, A Rigoni; Ronchese, P; Squarcia, S; Subieta, M; Vanini, S; Viesti, G; Zanuttigh, P; Zenoni, A; Zumerle, G

    2013-01-01

    The muon tomography technique, based on multiple Coulomb scattering of cosmic ray muons, has been proposed as a tool to detect the presence of high density objects inside closed volumes. A new and innovative method is presented in this paper to handle the density fluctuations (noise) of reconstructed images, that are a known problem of this technique. The effectiveness of our method is evaluated using experimental data obtained with a muon tomography prototype located at Legnaro National Laboratories (LNL) of the Istituto Nazionale di Fisica Nucleare (INFN). The results reported in this paper, obtained with real cosmic ray data, show that with appropriate image filtering and muon momentum classification, the muon tomography technique can detect in short times high density materials, such as lead, when surrounded by light or medium density material. A comparison with algorithms published in literature is also presented.

  2. A Tale of Two Electrons: Correlation at High Density

    CERN Document Server

    Loos, Pierre-François

    2010-01-01

    We review our recent progress in the determination of the high-density correlation energy $\\Ec$ in two-electron systems. Several two-electron systems are considered, such as the well known helium-like ions (helium), and the Hooke's law atom (hookium). We also present results regarding two electrons on the surface of a sphere (spherium), and two electrons trapped in a spherical box (ballium). We also show that, in the large-dimension limit, the high-density correlation energy of two opposite-spin electrons interacting {\\em via} a Coulomb potential is given by $\\Ec \\sim -1/(8D^2)$ for any radial external potential $V(r)$, where $D$ is the dimensionality of the space. This result explains the similarity of $\\Ec$ in the previous two-electron systems for $D=3$.

  3. Noise reduction in muon tomography for detecting high density objects

    Science.gov (United States)

    Benettoni, M.; Bettella, G.; Bonomi, G.; Calvagno, G.; Calvini, P.; Checchia, P.; Cortelazzo, G.; Cossutta, L.; Donzella, A.; Furlan, M.; Gonella, F.; Pegoraro, M.; Rigoni Garola, A.; Ronchese, P.; Squarcia, S.; Subieta, M.; Vanini, S.; Viesti, G.; Zanuttigh, P.; Zenoni, A.; Zumerle, G.

    2013-12-01

    The muon tomography technique, based on multiple Coulomb scattering of cosmic ray muons, has been proposed as a tool to detect the presence of high density objects inside closed volumes. In this paper a new and innovative method is presented to handle the density fluctuations (noise) of reconstructed images, a well known problem of this technique. The effectiveness of our method is evaluated using experimental data obtained with a muon tomography prototype located at the Legnaro National Laboratories (LNL) of the Istituto Nazionale di Fisica Nucleare (INFN). The results reported in this paper, obtained with real cosmic ray data, show that with appropriate image filtering and muon momentum classification, the muon tomography technique can detect high density materials, such as lead, albeit surrounded by light or medium density material, in short times. A comparison with algorithms published in literature is also presented.

  4. Origins and Impacts of High-Density Symmetry Energy

    CERN Document Server

    Li, Bao-An

    2016-01-01

    What is nuclear symmetry energy? Why is it important? What do we know about it? Why is it so uncertain especially at high densities? Can the total symmetry energy or its kinetic part be negative? What are the effects of three-body and/or tensor force on symmetry energy? How can we probe the density dependence of nuclear symmetry energy with terrestrial nuclear experiments? What observables of heavy-ion reactions are sensitive to the high-density behavior of nuclear symmetry energy? How does the symmetry energy affect properties of neutron stars, gravitational waves and our understanding about the nature of strong-field gravity? In this lecture, we try to answer these questions as best as we can based on some of our recent work and/or understanding of research done by others. This note summarizes the main points of the lecture.

  5. High density data storage principle, technology, and materials

    CERN Document Server

    Zhu, Daoben

    2009-01-01

    The explosive increase in information and the miniaturization of electronic devices demand new recording technologies and materials that combine high density, fast response, long retention time and rewriting capability. As predicted, the current silicon-based computer circuits are reaching their physical limits. Further miniaturization of the electronic components and increase in data storage density are vital for the next generation of IT equipment such as ultra high-speed mobile computing, communication devices and sophisticated sensors. This original book presents a comprehensive introduction to the significant research achievements on high-density data storage from the aspects of recording mechanisms, materials and fabrication technologies, which are promising for overcoming the physical limits of current data storage systems. The book serves as an useful guide for the development of optimized materials, technologies and device structures for future information storage, and will lead readers to the fascin...

  6. Fabrication of very high density fuel pellets of thorium dioxide

    Science.gov (United States)

    Shiratori, Tetsuo; Fukuda, Kosaku

    1993-06-01

    Very high density ThO 2 pellets were prepared without binders and lubricants from the ThO 2 powder originated by the thorium oxalate, which was aimed to simplify the fabrication process by skipping a preheat treatment. The as-received ThO 2 powder with a surface area of 4.56 m 2/g was ball-milled up to about 9 m 2/g in order to increase the green pellet density as high as possible. Both of the single-sided and the double-sided pressing were tested in the range from 2 to 5 t/cm 2 in the green pellet formation. Sintering temperature was such low as 1550°C. The pellet prepared in this experiment had a very high density in the range from about 96 to 98% TD without any cracks, in which a difference of the pellet density was not recognized in the single-sided pressing methods.

  7. Spontaneous magnetization in high-density quark matter

    DEFF Research Database (Denmark)

    Tsue, Yasuhiko; da Providência, João; Providência, Constanca;

    2015-01-01

    It is shown that spontaneous magnetization occurs due to the anomalous magnetic moments of quarks in high-density quark matter under the tensor-type four-point interaction. The spin polarized condensate for each flavor of quark appears at high baryon density, which leads to the spontaneous...... magnetization due to the anomalous magnetic moments of quarks. The implications for the strong magnetic field in compact stars is discussed....

  8. Polypropylene-(high density polyethylene) precipitation from stirred solutions

    OpenAIRE

    Esperidião,Maria Cecília Azevedo; Galembeck,Fernando

    1993-01-01

    Texto completo: acesso restrito. p.993–997 The fast precipitation of mixtures of polypropylene (PP) with high density polyethylene (HDPE) from decalin solutions is affected by the stirring rate of the solutions. With fast stirring, two types of precipitates were obtained viz. globules dispersed in the liquid phase and fibres adhering to the stirrer. Studies by i.r., WAXD, DSC and optical microscopy indicated that the fibrous precipitate is more birefringent, richer in HDPE and richer in th...

  9. BCS Theory of Hadronic Matter at High Densities

    DEFF Research Database (Denmark)

    Bohr, Henrik; Panda, Prafulla K.; Providencia, Constanca

    2012-01-01

    The equilibrium between the so-called 2SC and CFL phases of strange quark matter at high densities is investigated in the framework of a simple schematic model of the NJL type. Equal densities are assumed for quarks u, d and s. The 2SC phase is here described by a color-flavor symmetric state...... than is usual in NJL type models. This should be adequate if the relevant chemical potential does not exceed 0.6 GeV....

  10. Antrodia camphorata induces G(1) cell-cycle arrest in human premyelocytic leukemia (HL-60) cells and suppresses tumor growth in athymic nude mice.

    Science.gov (United States)

    Yang, Hsin-Ling; Kumar, K J Senthil; Kuo, Ya-Ting; Chang, Hebron C; Liao, Jiunn-Wang; Hsu, Li-Sung; Hseu, You-Cheng

    2014-09-01

    Antrodia camphorata is a well-known medicinal mushroom in Taiwan. The broth from a fermented culture of Antrodia camphorata (AC) has been shown to induce apoptosis in cultured human premyelocytic leukemia (HL-60) cells. In the present study, we examined the effects of AC on cell cycle arrest in vitro in HL-60 cells and on tumor regression in vivo using an athymic nude mouse model. We found that AC (20-80 μg mL(-1)) treatment significantly induced G1 cell-cycle arrest in HL-60 cells by reducing the levels of cyclin D1, CDK4, cyclin E, CDK2, cyclin A, and phosphorylation of retinoblastoma protein (p-Rb). Moreover, AC treatment led to significantly increased protein expression levels of CDK inhibitors, including p21(WAF1) and p15(NIK4B). Additionally, AC treatment markedly induced intracellular ROS generation and mitochondrial dysfunction in HL-60 cells. Furthermore, the in vivo study results revealed that AC treatment was effective in terms of delaying the tumor incidence in nude mice that had been inoculated with HL-60 cells as well as in reducing the tumor burden. Histological analysis confirmed that AC treatment significantly modulated the xenografted tumor progression as demonstrated by a reduction in mitotic cells. Our data strongly suggest that Antrodia camphorata could be an anti-cancer agent for human leukemia.

  11. High-density cervical ureaplasma urealyticum colonization in pregnant women

    Directory of Open Access Journals (Sweden)

    Ranđelović Gordana

    2006-01-01

    Full Text Available Background/aim: Ureaplasma urealyticum, a common commensal of the female lower genital tract, has been observed as an important opportunistic pathogen during pregnancy. The aims of this study were to determine the degree of cervical colonization with U. urealyticum in pregnant women with risk pregnancy and in pregnant women with normal term delivery and to evaluate the correlation between high-density cervical U. urealyticum colonization and premature rupture of membranes (PROM as well. Methods. This research was conducted on the samples comprising 130 hospitalized pregnant women with threatening preterm delivery and premature rupture of membranes. The control group consisted of 39 pregnant women with term delivery without PROM. In addition to standard bacteriological examination and performing direct immunofluorescence test to detect Chlamydia trachomatis, cervical swabs were also examined for the presence of U. urealyticum and Mycoplasma hominis by commercially available Mycofast Evolution 2 test (International Microbio, France. Results. The number of findings with isolated high-density U. urealyticum in the target group was 69 (53.08%, while in the control group was 14 (35.90%. Premature rupture of membranes (PROM occurred in 43 (33.08% examinees: 29 were pPROM, and 14 were PROM. The finding of U.urealyticum ≥104 was determined in 25 (58.14% pregnant women with rupture, 17 were pPROM, and 8 were PROM. There was statistically significant difference in the finding of high-density U. urealyticum between the pregnant women with PROM and the control group (χ² = 4.06, p < 0.05. U. urealyticum was predominant bacterial species found in 62.79% of isolates in the PROM cases, while in 32.56% it was isolated alone. Among the 49 pregnant women with preterm delivery, pPROM occurred in 29 (59.18% examinees, and in 70.83% of pregnant women with findings of high-density U. urealyticum pPROM was observed. Conclusion. Cervical colonization with U

  12. Density limits investigation and high density operation in EAST tokamak

    Science.gov (United States)

    Zheng, Xingwei; Li, Jiangang; Hu, Jiansheng; Liu, Haiqing; Jie, Yinxian; Wang, Shouxin; Li, Jiahong; Duan, Yanming; Li, Miaohui; Li, Yongchun; Zhang, Ling; Ye, Yang; Yang, Qingquan; Zhang, Tao; Cheng, Yingjie; Xu, Jichan; Wang, Liang; Xu, Liqing; Zhao, Hailin; Wang, Fudi; Lin, Shiyao; Wu, Bin; Lyu, Bo; Xu, Guosheng; Gao, Xiang; Shi, Tonghui; He, Kaiyang; Lan, Heng; Chu, Nan; Cao, Bin; Sun, Zhen; Zuo, Guizhong; Ren, Jun; Zhuang, Huidong; Li, Changzheng; Yuan, Xiaolin; Yu, Yaowei; Wang, Houyin; Chen, Yue; Wu, Jinhua; EAST Team

    2016-05-01

    Increasing the density in a tokamak is limited by the so-called density limit, which is generally performed as an appearance of disruption causing loss of plasma confinement, or a degradation of high confinement mode which could further lead to a H  →  L transition. The L-mode and H-mode density limit has been investigated in EAST tokamak. Experimental results suggest that density limits could be triggered by either edge cooling or excessive central radiation. The L-mode density limit disruption is generally triggered by edge cooling, which leads to the current profile shrinkage and then destabilizes a 2/1 tearing mode, ultimately resulting in a disruption. The L-mode density limit scaling agrees well with the Greenwald limit in EAST. The observed H-mode density limit in EAST is an operational-space limit with a value of 0.8∼ 0.9{{n}\\text{GW}} . High density H-mode heated by neutral beam injection (NBI) and lower hybrid current drive (LHCD) are analyzed, respectively. The constancy of the edge density gradients in H-mode indicates a critical limit caused perhaps by e.g. ballooning induced transport. The maximum density is accessed at the H  →  L transition which is generally caused by the excessive core radiation due to high Z impurities (Fe, Cu). Operating at a high density (>2.8× {{10}19} {{\\text{m}}-3} ) is favorable for suppressing the beam shine through NBI. High density H-mode up to 5.3× {{10}19}{{\\text{m}}-3}~≤ft(∼ 0.8{{n}\\text{GW}}\\right) could be sustained by 2 MW 4.6 GHz LHCD alone, and its current drive efficiency is studied. Statistics show that good control of impurities and recycling facilitate high density operation. With careful control of these factors, high density up to 0.93{{n}\\text{GW}} stable H-mode operation was carried out heated by 1.7 MW LHCD and 1.9 MW ion cyclotron resonance heating with supersonic molecular beam injection fueling.

  13. IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis:contribution of the PI-3' kinase/AKT pathway

    Institute of Scientific and Technical Information of China (English)

    Gregory B Carey; Elena Semenova; Xiulan Qi; Achsah D Keegan

    2007-01-01

    Interleukin-4(IL-4)promotes lymphocyte survival and protects primary lymphomas from apoptosis.Previous studies reported differential requirements for the signal transducer and activator of transcription 6(STAT6)and IRS2/phosphatidylinositol 3 kinase(PI-3K)signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis.In this study,we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31,a model B-cell lymphoma line.In CH31,anti-IgM treatment leads to the loss of mitochondrial membrane potential,phospho-Akt,phospho-CDK2,and c-myc protein.These losses are followed by massive induction ofp27Kip1 protein expression,cell cycle arrest,and apoptosis.Strikingly,IL-4 treatment prevented or reversed these changes.Furthermore,IL-4 suppressed the activation of caspases 9 and 3,and,in contrast to previous reports,induced the phosphorylation(deactivation)of BAD.IL-4 treatment also induced expression of BclxL,a STAT6-dependent gene.Pharmacologic inhibitors and dominant inhibitory forms of PI-3K andAkt abrogated the anti-apoptotic function of IL-4.These results suggest that the IL-4 receptor activates several signaling pathways,with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.

  14. Injectable, high-density collagen gels for annulus fibrosus repair: An in vitro rat tail model.

    Science.gov (United States)

    Borde, Brandon; Grunert, Peter; Härtl, Roger; Bonassar, Lawrence J

    2015-08-01

    A herniated intervertebral disc often causes back pain when disc tissue is displaced through a damaged annulus fibrosus. Currently, the only methods available for annulus fibrosus repair involve mechanical closure of defect, which does little to address biological healing in the damaged tissue. Collagen hydrogels are injectable and have been used to repair annulus defects in vivo. In this study, high-density collagen hydrogels at 5, 10, and 15 mg/mL were used to repair defects made to intact rat caudal intervertebral discs in vitro. A group of gels at 15 mg/mL were also cross-linked with riboflavin at 0.03 mM, 0.07 mM, or 0.10 mM. These cross-linked, high-density collagen gels maintained their presence in the defect under loading and contributed positively to the mechanical response of damaged discs. Discs exhibited increases to 95% of undamaged effective equilibrium and instantaneous moduli as well as up to fourfold decreases in effective hydraulic permeability from the damaged discs. These data suggest that high-density collagen gels may be effective at restoring mechanical function of injured discs as well as potential vehicles for the delivery of biological agents such as cells or growth factors that may aid in the repair of the annulus fibrosus.

  15. 4β-Hydroxywithanolide E from Physalis peruviana (golden berry inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

    Directory of Open Access Journals (Sweden)

    Guo Zong-Lun

    2010-02-01

    Full Text Available Abstract Background The crude extract of the fruit bearing plant, Physalis peruviana (golden berry, demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown. Methods Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299 using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE assay was used to evaluate the DNA damage due to the drug. Results It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p p 50 of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h. Conclusions In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.

  16. High-Density Stacked Ru Nanocrystals for Nonvolatile Memory Application

    Institute of Scientific and Technical Information of China (English)

    MAO Ping; ZHANG Zhi-Gang; PAN Li-Yang; XU Jun; CHEN Pei-Yi

    2009-01-01

    @@ Stacked ruthenium (Ru) nanocrystals (NCs) are formed by rapid thermal annealing for the whole gate stacks and embedded in memory structure, which is compatible with conventional CMOS technology. Ru NCs with high density (3×1012 cm-2 ), small size (2-4 nm) and good uniformity both in aerial distribution and morphology are formed. Attributed to the higher surface trap density, a memory window of 5.2 V is obtained with stacked Ru NCs in comparison to that of 3.5 V with single-layer samples. The stacked Ru NCs device also exhibits much better retention performance because of Coulomb blockade and vertical uniformity between stacked Ru NCs.

  17. High density QCD and entropy production at heavy ion colliders

    CERN Document Server

    Kinder-Geiger, Klaus

    1994-01-01

    The role of entropy production in the context of probing QCD properties at high densities and finite temperatures in ultra-relativistic collisions of heavy nuclei is inspected. It is argued that the entropy generated in these reactions provides a powerful tool to investigate the space-time evolution and the question whether and how a deconfined plasma of quarks and gluons is formed. I will address the questions how entropy is produced, and how it is measurable. The uncertainties in predicting the different contributions to the total entropy and particle multiplicities during the course of heavy ion collisions are also discussed.

  18. High Density Thermal Energy Storage with Supercritical Fluids

    Science.gov (United States)

    Ganapathi, Gani B.; Wirz, Richard

    2012-01-01

    A novel approach to storing thermal energy with supercritical fluids is being investigated, which if successful, promises to transform the way thermal energy is captured and utilized. The use of supercritical fluids allows cost-affordable high-density storage with a combination of latent heat and sensible heat in the two-phase as well as the supercritical state. This technology will enhance penetration of several thermal power generation applications and high temperature water for commercial use if the overall cost of the technology can be demonstrated to be lower than the current state-of-the-art molten salt using sodium nitrate and potassium nitrate eutectic mixtures.

  19. Antarctic marine gravity field from high-density satellite altimetry

    Science.gov (United States)

    Sandwell, David T.

    1992-01-01

    High-density (about 2-km profile spacing) Geosat/GM altimetry profiles were obtained for Antarctic waters (6-deg S to 72 deg S) and converted to vertical gravity gradient, using Laplace's equation to directly calculate gravity gradient from vertical deflection grids and Fourier analysis to construct gravity anomalies from two vertical deflection grids. The resultant gravity grids have resolution and accuracy comparable to shipboard gravity profiles. The obtained gravity maps display many interesting and previously uncharted features, such as a propagating rift wake and a large 'leaky transform' along the Pacific-Antarctic Rise.

  20. A Cherenkov Radiation Detector with High Density Aerogels

    CERN Document Server

    Cremaldi, Lucien; Sonnek, Peter; Summers, Donald J; Reidy, Jim

    2009-01-01

    We have designed a threshold Cherenkov detector at the Rutherford-Appleton Laboratory to identify muons with momenta between 230 and 350 MeV/c. We investigated the properties of three aerogels for the design. The nominal indexes of refraction were n = 1.03, 1.07, 1.12, respectively. Two of the samples are of high density aerogel not commonly used for Cherenkov light detection. We present results of an examination of some optical properties of the aerogel samples and present basic test beam results.

  1. Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

    Science.gov (United States)

    McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

    2014-01-01

    We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

  2. The European Arrest Warrant

    Directory of Open Access Journals (Sweden)

    Minodora-Ioana Balan-Rusu

    2012-05-01

    Full Text Available In the paper it is generally examined the institution of the European arrest warrant according to the latest changes and additions through the adoption of a new European legislative act. The paper is a continuation of research in the area of judicial cooperation in criminal matters in the European Union. It may be useful to the judicial bodies with the responsibilities of issuing and executing a specific European arrest warrant and to academics and students in law schools. The research results, the essential contribution, the originality consist of the general examination of the institution, the critical remarks and proposals for amending and completing certain provisions insufficiently clear.

  3. A polyphenolic fraction from grape seeds causes irreversible growth inhibition of breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases activation and inducing G1 arrest and differentiation.

    Science.gov (United States)

    Agarwal, C; Sharma, Y; Zhao, J; Agarwal, R

    2000-07-01

    In recent years, significant emphasis is being placed on identifying naturally occurring cancer preventive and interventive agents. In this regard, a polyphenolic fraction isolated from grape seeds (hereafter referred as GSP) has recently been shown by us and others to prevent tumorigenesis in mouse skin models. Chemical analysis of GSP has shown that it is largely constituted with procyanidins that are strong antioxidants. Breast cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths in United States women. Accordingly, here we investigated the effect of GSP on mitogenic signaling and regulators of cell cycle and apoptosis as molecular targets for the growth arrest, apoptotic death, and/or differentiation of estrogen-independent MDA-MB468 human breast carcinoma cells. Treatment of cells with GSP (at 25-, 50-, and 75-microg/ml doses for 1-3 days) resulted in a highly significant inhibition (90% to complete, P cancer in humans.

  4. Simulating deposition of high density tailings using smoothed particle hydrodynamics

    Science.gov (United States)

    Babaoglu, Yagmur; Simms, Paul H.

    2017-08-01

    Tailings are a slurry of silt-sized residual material derived from the milling of rock. High density (HD) tailings are tailings that have been sufficiently dewatered to a point where they exhibit a yield stress upon deposition. They form gently sloped stacks on the surface when deposited; this eliminates or minimizes the need for dams or embankments for containment. Understanding the flow behaviour of high density tailings is essential for estimating the final stack geometry and overall slope angle. This paper focuses on modelling the flow behaviour of HD tailings using smoothed particle hydrodynamics (SPH) method incorporating a `bi-viscosity' model to simulate the non-Newtonian behaviour. The model is validated by comparing the numerical results with bench scale experiments simulating single or multi-layer deposits in two-dimensions. The results indicate that the model agreed fairly well with the experimental work, excepting some repulsion of particles away from the bottom boundary closer to the toe of the deposits. Novel aspects of the work, compared to other simulation of Bingham fluids by SPH, are the simulation of multilayer deposits and the use of a stopping criteria to characterize the rest state.

  5. Ultra-Stretchable Interconnects for High-Density Stretchable Electronics

    Directory of Open Access Journals (Sweden)

    Salman Shafqat

    2017-09-01

    Full Text Available The exciting field of stretchable electronics (SE promises numerous novel applications, particularly in-body and medical diagnostics devices. However, future advanced SE miniature devices will require high-density, extremely stretchable interconnects with micron-scale footprints, which calls for proven standardized (complementary metal-oxide semiconductor (CMOS-type process recipes using bulk integrated circuit (IC microfabrication tools and fine-pitch photolithography patterning. Here, we address this combined challenge of microfabrication with extreme stretchability for high-density SE devices by introducing CMOS-enabled, free-standing, miniaturized interconnect structures that fully exploit their 3D kinematic freedom through an interplay of buckling, torsion, and bending to maximize stretchability. Integration with standard CMOS-type batch processing is assured by utilizing the Flex-to-Rigid (F2R post-processing technology to make the back-end-of-line interconnect structures free-standing, thus enabling the routine microfabrication of highly-stretchable interconnects. The performance and reproducibility of these free-standing structures is promising: an elastic stretch beyond 2000% and ultimate (plastic stretch beyond 3000%, with <0.3% resistance change, and >10 million cycles at 1000% stretch with <1% resistance change. This generic technology provides a new route to exciting highly-stretchable miniature devices.

  6. The European arrest warrant

    Directory of Open Access Journals (Sweden)

    Đurđić Vojislav

    2012-01-01

    Full Text Available The paper portrays the new European Union extradition system, established by the Framework Decision on the European arrest warrant and the surrender procedures between Member States of 2002. In the introductory remarks, the author explains the formation and development of the traditional extradition procedure, depicts relevant legal sources, and points to its flaws, which boil down to tardiness and inefficiency. The main author's standpoint is that the European arrest warrant is based on mutual trust in the member-states' legal systems, and that it depoliticizes the extradition procedure by transforming interstate cooperation into cooperation between member - states' law enforcement authorities. On these grounds, the author determines the nature of this new legal institute, that introduces radical changes into the paradigm of the classical extradition, and explains its main features as well as the scope of application. Further on, the paper explores the conditions for issuance of the European arrest warrant, which are proscribed by negative formulations - as absolute and relative obstacles for extradition. Finally, the author explains the standardized formal elements of the European arrest warrant content, which should make its application easier and more expeditious.

  7. Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV‐3 and A-2780 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Piotrowska, Hanna; Myszkowski, Krzysztof; Ziółkowska, Alicja [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kulcenty, Katarzyna [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Wierzchowski, Marcin [Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan (Poland); Kaczmarek, Mariusz [Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan (Poland); Murias, Marek [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kwiatkowska-Borowczyk, Eliza [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Poznan (Poland); Jodynis-Liebert, Jadwiga, E-mail: liebert@ump.edu.pl [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland)

    2012-08-15

    In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC{sub 50} = 0.71 μM) and SKOV-3 (IC{sub 50} = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.

  8. Runway Arrested Landing Site (RALS)

    Data.gov (United States)

    Federal Laboratory Consortium — The Runway Arrested Landing Site includes an underground complex located on a Mod 2, Mod 3, and Mod 3+ arresting gear and are located under the runway and accurately...

  9. Genotype by environment interaction for adult body weights of shrimp Penaeus vannamei when grown at low and high densitie

    Directory of Open Access Journals (Sweden)

    Famula Thomas R

    2008-09-01

    Full Text Available Abstract Shrimp is one of few marine species cultured worldwide for which several selective breeding programs are being conducted. One environmental factor that can affect the response to selection in breeding programs is the density at which the shrimp are cultured (low-medium-high. Phenotypic plasticity in the growth response to different densities might be accompanied by a significant genotype by environment interaction, evidenced by a change in heritabilities between environments and by a genetic correlation less than one for a unique trait between environments. Our goal was to understand whether different growth densities affect estimates of those genetic parameters for adult body weight (BW in the Pacific white shrimp (Penaeus vannamei. BW heritabilities were significantly different between environments, with the largest at high density. These differences resulted from both an increased additive genetic variance and a decreased environmental variance when grown at high density. The genetic correlation between BWs at the two environmental conditions was significantly less than one. Whereas these results might be suggestive for carrying out shrimp selective breeding for BW under high density conditions, further understanding of genetic correlations between growth and reproductive traits within a given environment is necessary, as there are indications of reduced reproductive fitness for shrimp grown at high densities.

  10. CARI III Inhibits Tumor Growth in a Melanoma-Bearing Mouse Model through Induction of G0/G1 Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Hye-Jin Park

    2014-09-01

    Full Text Available Mushroom-derived natural products have been used to prevent or treat cancer for millennia. In this study, we evaluated the anticancer effects of CARI (Cell Activation Research Institute III, which consists of a blend of mushroom mycelia from Phellinus linteus grown on germinated brown rice, Inonotus obliquus grown on germinated brown rice, Antrodia camphorata grown on germinated brown rice and Ganoderma lucidum. Here, we showed that CARI III exerted anti-cancer activity, which is comparable to Dox against melanoma in vivo. B16F10 cells were intraperitoneally injected into C57BL6 mice to develop solid intra-abdominal tumors. Three hundred milligrams of the CARI III/kg/day p.o. regimen reduced tumor weight, comparable to the doxorubicin (Dox-treated group. An increase in life span (ILS% = 50.88% was observed in the CARI III-administered group, compared to the tumor control group. CARI III demonstrates anti-proliferative activity against B16F10 melanoma cells through inducing G0/G1 cell cycle arrest. CARI III inhibits the expression of cyclin D1, CDK4 and CDK2 and induces p21. Therefore, CARI III could be a potential chemopreventive supplement to melanoma patients.

  11. Aqueous extracts of the edible Gracilaria tenuistipitata are protective against H₂O₂-induced DNA damage, growth inhibition, and cell cycle arrest.

    Science.gov (United States)

    Yang, Jing-Iong; Yeh, Chi-Chen; Lee, Jin-Ching; Yi, Szu-Cheng; Huang, Hurng-Wern; Tseng, Chao-Neng; Chang, Hsueh-Wei

    2012-06-13

    Potential antioxidant properties of an aqueous extract of the edible red seaweed Gracilaria tenuistipitata (AEGT) against oxidative DNA damage were evaluated. The AEGT revealed several antioxidant molecules, including phenolics, flavonoids and ascorbic acid. In a cell-free assay, the extract exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity that significantly reduced H₂O₂-induced plasmid DNA breaks in a dose-response manner (P < 0.001). The AEGT also suppressed H₂O₂-induced oxidative DNA damage in H1299 cells by reducing the percentage of damaged DNA in a dose-response manner (P < 0.001) as measured by a modified alkaline comet-nuclear extract (comet-NE) assay. The MTT assay results showed that AEGT confers significant protection against H₂O₂-induced cytotoxicity and that AEGT itself is not cytotoxic (P < 0.001). Moreover, H₂O₂-induced cell cycle G2/M arrest was significantly released when cells were co-treated with different concentrations of AEGT (P < 0.001). Taken together, these findings suggest that edible red algae Gracilaria water extract can prevent H₂O₂-induced oxidative DNA damage and its related cellular responses.

  12. Alpinia pricei Rhizome Extracts Induce Cell Cycle Arrest in Human Squamous Carcinoma KB Cells and Suppress Tumor Growth in Nude Mice

    Directory of Open Access Journals (Sweden)

    You-Cheng Hseu

    2011-01-01

    Full Text Available Alpinia pricei has been shown to induce apoptosis in human squamous carcinoma (KB cells. In this study, we report the effectiveness of the ethanol (70% extracts of A. pricei rhizome (AP extracts in terms of tumor regression as determined using both in vitro cell culture and in vivo athymic nude mice models of KB cells. We found that the AP extract (25–200 μg/mL treatment decreased the proliferation of KB cells by arresting progression through the G2/M phase of the cell cycle. This cell cycle blockade was associated with reductions in cyclin A and B1, Cdc2, and Cdc25C, and increased p21/WAF1, Wee1, p53 and phospho-p53 (p-p53 in a dose- and time-dependent manner. Moreover, we found that AP extract treatment decreased metalloproteinase-9 (MMP-9 and urokinase plasminogen activator (u-PA expression, while expression of their endogenous inhibitors, tissue inhibitor of MMP-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1, were increased in KB cells. Furthermore, AP extract treatment effectively delayed tumor incidence in nude mice inoculated with KB cells and reduced the tumor burden. AP extract treatment also induced apoptotic DNA fragmentation, as detected by in situ TUNEL staining. Thus, A. pricei may possess antitumor activity in human squamous carcinoma (KB cells.

  13. Dactylone inhibits epidermal growth factor-induced transformation and phenotype expression of human cancer cells and induces G1-S arrest and apoptosis.

    Science.gov (United States)

    Fedorov, Sergey N; Shubina, Larisa K; Bode, Ann M; Stonik, Valentin A; Dong, Zigang

    2007-06-15

    The marine natural chamigrane-type sesquiterpenoid, dactylone, is closely related to secondary metabolites of some edible species of red algae. In the present study, the effect of dactylone was tested on the mouse skin epidermal JB6 P+ Cl41 cell line and its stable transfectants as well as on several human tumor cell lines, including lung (H460), colon (HCT-116), and skin melanomas (SK-MEL-5 and SK-MEL-28). This natural product was effective at nontoxic doses as a cancer-preventive agent, which exerted its actions, at least in part, through the inhibition of cyclin D3 and Cdk4 expression and retinoblastoma tumor suppressor protein (Rb) phosphorylation. The inhibition of these cell cycle components was followed by cell cycle arrest at the G1-S transition with subsequent p53-independent apoptosis. Therefore, these data showed that application of dactylone and related compounds may lead to decreased malignant cell transformation and/or decreased tumor cell proliferation.

  14. NF-kappa B signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells

    NARCIS (Netherlands)

    Yao, Jun; Duan, Li; Fan, Mingwen; Wu, Xinxing

    2006-01-01

    The HDAC inhibitor Trichostatin A (TSA) exhibits antiturnour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113

  15. A ferroelectric DRAM cell for high-density NVRAM's

    Science.gov (United States)

    Moazzami, Reza; Hu, Chenming; Shepherd, William H.

    1990-10-01

    The operation of a ferroelectric DRAM (dynamic random-access memory) cell for nonvolatile RAM (NVRAM) applications is described. Because polarization reversal only occurs during nonvolatile store/recall operations and not during read/write operations, ferroelectric fatigue is not a serious endurance problem. For a 3-V power supply, the worst-case effective silicon dioxide thickness of the unoptimized lead zirconate titanate film studied is less than 1.7 nm. The resistivity and endurance properties of ferroelectric films can be optimized by modifying the composition of the film. This cell can be the basis of a very-high-density NVRAM with practically no read/write cycle limit and at least 10 to the 10th nonvolatile store/recall cycles.

  16. [Cholesterol in serum high density lipoprotein fraction (author's transl)].

    Science.gov (United States)

    Schatz, C; Jeanblanc, B; Offner, M

    1980-11-22

    The risk of atheroma can be assessed and valid epidemiological surveys can be carried out by measuring cholesterol in serum high density lipoprotein fraction (HDL) and calculating the HDL cholesterol: VLDL + LDL ratio. This was done in 39 patients free from surgically confirmed atheromatous lesions and in 51 patients presenting with such lesions. Of the four different techniques used for separation in these patients (ultracentrifugation, precipitation with heparin-Mn2+, precipitation with phosphotungstate-Mg2+ and electrophoresis), precipitation with phosphotungstate-Mg/2+ seems to be the most suitable, since there is no degradation of the HDL fraction as during electrophoresis on polyacrylamide gel, and less floculation of the supernatant after separation. Contrary to ultracentrifugation, which requires sophisticated equipment and good technical skill, the technique is easily carried out.

  17. High-density polyethylene dosimetry by transvinylene FTIR analysis

    DEFF Research Database (Denmark)

    McLaughlin, W.L.; Silverman, J.; Al-Sheikhly, M.

    1999-01-01

    . The transvinylene response in air to gamma radiation is linear with dose and has relatively low yield compared with the response to electrons, whereas the response in deaerated polyethylene samples is also linear, but is more sensitive, and has negligible dose-rate dependence in its response to gamma rays...... and electrons. The useful dose range of 0.053 cm thick high-density polyethylene film (rho = 0.961 g cm(-3); melt index = 0.8 dg min(-1)), for irradiations by (60)Co gamma radiation and 2.0 and 0.4 MeV electron beams in deaerated atmosphere (Na gas), is about 50-10(3) kGy for FTIR transvinylene...

  18. Scoping study. High density polyethylene (HDPE) in salstone service

    Energy Technology Data Exchange (ETDEWEB)

    Phifer, Mark A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2005-02-18

    An evaluation of the use of high density polyethylene (HDPE) geomembranes in Saltstone service has been conducted due to the potential benefits that could be derived from such usage. HDPE is one of the simplest hydrocarbon polymers and one of the most common polymers utilized in the production of geomembranes, which means that its costs are relatively low. Additionally, HDPE geomembranes have an extremely low permeability and an extremely low water vapor diffusional flux, which means that it is a good barrier to contaminant transport. The primary consideration in association with HDPE geomembranes in Saltstone service is the potential impact of Saltstone on the degradation of the HDPE geomembranes. Therefore, the evaluation documented herein has primarily focused upon the potential HDPE degradation in Saltstone service.

  19. The alterations in high density polyethylene properties with gamma irradiation

    Science.gov (United States)

    Zaki, M. F.; Elshaer, Y. H.; Taha, Doaa. H.

    2017-10-01

    In the present investigation, high density polyethylene (HDPE) polymer has been used to study the alterations in its properties under gamma-irradiation. Physico-chemical properties have been investigated with different spectroscopy techniques, Fourier Transform Infrared spectroscopy (FTIR), X-ray diffraction (XRD), biocompatibility properties, as well as, mechanical properties change. The FT-IR analysis shows the formation of new band at 1716 cm-1 that is attributed to the oxidation of irradiated polymer chains, which is due to the formation of carbonyl groups (C˭O). XRD patterns show that a decrease in the crystallite size and increase in the Full Width at Half Maximum (FWHM). This means that the crystallinity of irradiated samples is decreased with increase in gamma dose. The contact angle measurements show an increase in the surface free energy as the gamma irradiation increases. The measurements of mechanical properties of irradiated HDPE samples were discussed.

  20. High density operation for reactor-relevant power exhaust

    Science.gov (United States)

    Wischmeier, M.

    2015-08-01

    With increasing size of a tokamak device and associated fusion power gain an increasing power flux density towards the divertor needs to be handled. A solution for handling this power flux is crucial for a safe and economic operation. Using purely geometric arguments in an ITER-like divertor this power flux can be reduced by approximately a factor 100. Based on a conservative extrapolation of current technology for an integrated engineering approach to remove power deposited on plasma facing components a further reduction of the power flux density via volumetric processes in the plasma by up to a factor of 50 is required. Our current ability to interpret existing power exhaust scenarios using numerical transport codes is analyzed and an operational scenario as a potential solution for ITER like divertors under high density and highly radiating reactor-relevant conditions is presented. Alternative concepts for risk mitigation as well as strategies for moving forward are outlined.

  1. Ultracold molecular Rydberg physics in a high density environment

    CERN Document Server

    Eiles, Matthew T; Robicheaux, F; Greene, Chris H

    2016-01-01

    Sufficiently high densities in Bose-Einstein condensates provide favorable conditions for the production of ultralong-range polyatomic molecules consisting of one Rydberg atom and a number of neutral ground state atoms. The chemical binding properties and electronic wave functions of these exotic molecules are investigated analytically via hybridized diatomic states. The effects of the molecular geometry on the system's properties are studied through comparisons of the adiabatic potential curves and electronic structures for both symmetric and randomly configured molecular geometries. General properties of these molecules with increasing numbers of constituent atoms and in different geometries are presented. These polyatomic states have spectral signatures that lead to non-Lorentzian line-profiles.

  2. Single-Readout High-Density Memristor Crossbar

    KAUST Repository

    Zidan, M. A.

    2016-01-07

    High-density memristor-crossbar architecture is a very promising technology for future computing systems. The simplicity of the gateless-crossbar structure is both its principal advantage and the source of undesired sneak-paths of current. This parasitic current could consume an enormous amount of energy and ruin the readout process. We introduce new adaptive-threshold readout techniques that utilize the locality and hierarchy properties of the computer-memory system to address the sneak-paths problem. The proposed methods require a single memory access per pixel for an array readout. Besides, the memristive crossbar consumes an order of magnitude less power than state-of-the-art readout techniques.

  3. Characterization of high density through silicon vias with spectral reflectometry.

    Science.gov (United States)

    Ku, Yi-Sha; Huang, Kuo Cheng; Hsu, Weite

    2011-03-28

    Measurement and control is an important step for production-worthy through silicon vias etch. We demonstrate the use and enhancement of an existing wafer metrology tool, spectral reflectometer by implementing novel theoretical model and measurement algorithm for high density through-silicon via (HDTSV) inspection. It is capable of measuring depth and depth variations of array vias by Discrete Fourier Transform (DFT) analysis in one shot measurement. Surface roughness of via bottom can also be extracted by scattering model fitting. Our non-destructive solution can measure TSV profile diameters as small as 5 μm and aspect ratios greater than 13:1. The measurement precision is in the range of 0.02 μm. Metrology results from actual 3D interconnect processing wafers are presented.

  4. Microelectromechanical high-density energy storage/rapid release system

    Science.gov (United States)

    Rodgers, M. Steven; Allen, James J.; Meeks, Kent D.; Jensen, Brian D.; Miller, Samuel L.

    1999-08-01

    One highly desirable characteristic of electrostatically driven microelectromechanical systems (MEMS) is that they consume very little power. The corresponding drawback is that the force they produce may be inadequate for many applications. It has previously been demonstrated that gear reduction units or microtransmissions can substantially increase the torque generated by microengines. Operating speed, however, is also reduced by the transmission gear ratio. Some applications require both high speed and high force. If this output is only required for a limited period of time, then energy could be stored in a mechanical system and rapidly released upon demand. We have designed, fabricated, and demonstrated a high-density energy storage/rapid release system that accomplishes this task. Built using a 5-level surface micromachining technology, the assembly closely resembles a medieval crossbow. Energy releases on the order of tens of nanojoules have already been demonstrated, and significantly higher energy systems are under development.

  5. High-density avalanche chambers for positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Manfrass, P.; Enghardt, W.; Fromm, W.D.; Wohlfarth, D.; Hohmuth, K.

    1988-12-15

    A positron tomograph for radiopharmaceutical and medical research is under construction. In its final stage it will cover six high-density avalanche chambers (HIDAC) in a hexagonal arrangement. Each detector with a sensitive area of 50x28 cm/sup 2/ will consist of a stack of four pairs of multihole photon-to-electron converters with a multiwire proportional counter (MWPC) in between. An experimental investigation of detector properties as time and spatial resolutions as well as detector efficiency in dependence to converter structure, electric field strength and counting gas mixture preceded the final design of these detectors. Results of these studies are outlined. Furthermore, longitudinal tomograms taken with a stationary test camera are presented.

  6. The Pulsed High Density Experiment (PHDX) Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Slough, John P. [Univ. of Washington, Seattle, WA (United States); Andreason, Samuel [Univ. of Washington, Seattle, WA (United States)

    2017-04-27

    The purpose of this paper is to present the conclusions that can be drawn from the Field Reversed Configuration (FRC) formation experiments conducted on the Pulsed High Density experiment (PHD) at the University of Washington. The experiment is ongoing. The experimental goal for this first stage of PHD was to generate a stable, high flux (>10 mWb), high energy (>10 KJ) target FRC. Such results would be adequate as a starting point for several later experiments. This work focuses on experimental implementation and the results of the first four month run. Difficulties were encountered due to the initial on-axis plasma ionization source. Flux trapping with this ionization source acting alone was insufficient to accomplish experimental objectives. Additional ionization methods were utilized to overcome this difficulty. A more ideal plasma source layout is suggested and will be explored during a forthcoming work.

  7. High-density percutaneous chronic connector for neural prosthetics

    Science.gov (United States)

    Shah, Kedar G.; Bennett, William J.; Pannu, Satinderpall S.

    2015-09-22

    A high density percutaneous chronic connector, having first and second connector structures each having an array of magnets surrounding a mounting cavity. A first electrical feedthrough array is seated in the mounting cavity of the first connector structure and a second electrical feedthrough array is seated in the mounting cavity of the second connector structure, with a feedthrough interconnect matrix positioned between a top side of the first electrical feedthrough array and a bottom side of the second electrical feedthrough array to electrically connect the first electrical feedthrough array to the second electrical feedthrough array. The two arrays of magnets are arranged to attract in a first angular position which connects the first and second connector structures together and electrically connects the percutaneously connected device to the external electronics, and to repel in a second angular position to facilitate removal of the second connector structure from the first connector structure.

  8. Methods and systems for rapid prototyping of high density circuits

    Science.gov (United States)

    Palmer, Jeremy A.; Davis, Donald W.; Chavez, Bart D.; Gallegos, Phillip L.; Wicker, Ryan B.; Medina, Francisco R.

    2008-09-02

    A preferred embodiment provides, for example, a system and method of integrating fluid media dispensing technology such as direct-write (DW) technologies with rapid prototyping (RP) technologies such as stereolithography (SL) to provide increased micro-fabrication and micro-stereolithography. A preferred embodiment of the present invention also provides, for example, a system and method for Rapid Prototyping High Density Circuit (RPHDC) manufacturing of solderless connectors and pilot devices with terminal geometries that are compatible with DW mechanisms and reduce contact resistance where the electrical system is encapsulated within structural members and manual electrical connections are eliminated in favor of automated DW traces. A preferred embodiment further provides, for example, a method of rapid prototyping comprising: fabricating a part layer using stereolithography and depositing thermally curable media onto the part layer using a fluid dispensing apparatus.

  9. Thermolysis of High-Density Polyethylene to Petroleum Products

    Directory of Open Access Journals (Sweden)

    Sachin Kumar

    2013-01-01

    Full Text Available Thermal degradation of plastic polymers is becoming an increasingly important method for the conversion of plastic materials into valuable chemicals and oil products. In this work, virgin high-density polyethylene (HDPE was chosen as a material for pyrolysis. A simple pyrolysis reactor system has been used to pyrolyse virgin HDPE with an objective to optimize the liquid product yield at a temperature range of 400°C to 550°C. The chemical analysis of the HDPE pyrolytic oil showed the presence of functional groups such as alkanes, alkenes, alcohols, ethers, carboxylic acids, esters, and phenyl ring substitution bands. The composition of the pyrolytic oil was analyzed using GC-MS, and it was found that the main constituents were n-Octadecane, n-Heptadecane, 1-Pentadecene, Octadecane, Pentadecane, and 1-Nonadecene. The physical properties of the obtained pyrolytic oil were close to those of mixture of petroleum products.

  10. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  11. Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

    Science.gov (United States)

    Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

    2017-02-01

    Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage.

  12. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Qing Yang

    Full Text Available Resveratrol, a naturally occurring polyphenolic compound, has been reported to exert anticancer activity by affecting diverse molecular targets. In this study, we examined the effects and the underlying mechanisms of resveratrol on gastric cancer. We found that resveratrol inhibited the proliferation of gastric cancer cells in a dose-dependent manner. At the concentration of 25 and 50 µM, resveratrol inhibited the cell viability and diminished the clonogenic potential of gastric cancer cells. Resveratrol treatment arrested gastric cancer cells in the G1 phase and led to senescence instead of apoptosis. Regulators of the cell cycle and senescence pathways, including cyclin D1, cyclin-dependent kinase (CDK4 and 6, p21 and p16, were dysregulated by resveratrol treatment. The inhibitory effects of resveratrol on gastric cancer were also verified in vivo using a nude mice xenograft model. Resveratrol (40 mg/kg/d exerted inhibitory activities on gastric cancer development and significantly decreased the fractions of Ki67-positive cells in the tumor specimens from the nude mice. After resveratrol treatment, the induction of senescence and the changes in the expression of the regulators involved in the cell cycle and senescence pathways were similar to what we observed in vitro. However, the depletion of Sirtuin (Sirt1 reversed the above-described effects of resveratrol both in vitro and in vivo. Our data suggest that resveratrol inhibits gastric cancer in a Sirt1-dependent manner and provide detailed evidence for the possibility of applying resveratrol in gastric cancer prevention and therapy.

  13. Fisetin inhibits growth, induces G₂ /M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation.

    Science.gov (United States)

    Pal, Harish C; Sharma, Samriti; Elmets, Craig A; Athar, Mohammad; Afaq, Farrukh

    2013-07-01

    Non-melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5-80 μm) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G₂ /M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2; Bcl-xL and Mcl-1); (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP-ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Fisetin inhibits growth, induces G2/M arrest and apoptosis of human epidermoid carcinoma A431 cells: Role of mitochondrial membrane potential disruption and consequent caspases activation

    Science.gov (United States)

    Pal, Harish C.; Sharma, Samriti; Elmets, Craig A.; Athar, Mohammad; Afaq, Farrukh

    2013-01-01

    Non-melanoma skin cancers (NMSCs) one of the most common neoplasms causes serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3′,4′,7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and anti-proliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fistein (5-80 μM) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G2/M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2, Bcl-xL and Mcl-1), (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad), (iii) disruption of mitochondrial potential, (iv) release of cytchrome c and Smac/DIABLO from mitochondria, (v) activation of caspases, and (vi) cleavage of PARP protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs. PMID:23800058

  15. Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21(WAF1/CIP1) expression.

    Science.gov (United States)

    Tseng, Tsui-Hwa; Chien, Ming-Hsien; Lin, Wea-Lung; Wen, Yu-Ching; Chow, Jyh-Ming; Chen, Chi-Kuan; Kuo, Tsang-Chih; Lee, Wei-Jiunn

    2017-02-01

    Apigenin (4',5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21(WAF1/CIP1) and increased the interaction of p21(WAF1/CIP1) with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21(WAF1/CIP1) promoter region, resulting in the increase of p21(WAF1/CIP1) transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21(WAF1/CIP1) and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017.

  16. Effects of gamma irradiation on polypropylene, polypropylene + high density polyethylene and polypropylene + high density polyethylene + wood flour

    Energy Technology Data Exchange (ETDEWEB)

    Reyes, J.; Albano, C.; Davidson, E.; Poleo, R. [Universidad Central de Venezuela, Caracas (Venezuela). Escuela de Quimica; Gonzalez, J.; Ichazo, M. [Universidad Simon Bolivar, Dept. de Mecanica, Caracas (Venezuela); Chipara, M. [Research Institute for Electrotechnics, Bucharest (Romania)

    2001-04-01

    The effect of the gamma-irradiation on the mechanical properties of the composites, Polypropylene (PP), PP+high density Polyethylene (HDPE), PP+ HDPE+wood flour, where HDPE is virgin and recycled, was studied. This paper discusses the behavior of the composites after exposure to various doses of gamma irradiation (1-7 MRads) in the presence of oxygen. The dependence of mechanical properties on the integral dose for a constant dose rate of 0.48 MRads/h confirms the influence of the irradiation. Strong effects on the elongation at break and break strength is noticed. The mathematical analysis suggests for the PP+r-HDPE a bimolecular process of the elongation at break. On the order hand, for the PP+HDPE a complex process is represented for a three exponential equation. (orig.)

  17. Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1

    Directory of Open Access Journals (Sweden)

    R.A. Roela

    2003-08-01

    Full Text Available Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO, an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control, as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells, alpha3 (93.3 ± 7.0%, alpha5 (50.4 ± 12.0% and alpha6 (34.1 ± 4.9% integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0% and fibronectin (40.0 ± 2.0% substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5% while simultaneously reducing alpha5 (24.2 ± 19% and alpha6 (14.3 ± 10.8% expression as well as c-myc mRNA (7-fold, the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells, was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

  18. Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1).

    Science.gov (United States)

    Roela, R A; Brentani, M M; Katayama, M L H; Reis, M; Federico, M H H

    2003-08-01

    Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of beta 1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO), an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control), as shown by flow cytometry and monoclonal antibodies, expressed alpha 2 (63.8 11.3% positive cells), alpha 3 (93.3 7.0%), alpha 5 (50.4 12.0%) and alpha 6 (34.1 4.9%) integrins but not alpha1, alpha 4, alpha v or 4. Cells adhered well to laminin-1 (73.4 6.0%) and fibronectin (40.0 2.0%) substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha 2, alpha 3 and alpha 6 mediated laminin-1 adhesion, but neither alpha 3 nor alpha 5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 2.4% vs DMSO: 70.7 2.5%) while simultaneously reducing alpha 5 (24.2 19%) and alpha 6 (14.3 10.8%) expression as well as c-myc mRNA (7-fold), the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha 3 and alpha 5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 2 cells vs DMSO: 64 6 cells), was blocked by an antibody against alpha 6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

  19. Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling

    National Research Council Canada - National Science Library

    Riwanto, Meliana; Rohrer, Lucia; Roschitzki, Bernd; Besler, Christian; Mocharla, Pavani; Mueller, Maja; Perisa, Damir; Heinrich, Kathrin; Altwegg, Lukas; von Eckardstein, Arnold; Lüscher, Thomas F; Landmesser, Ulf

    2013-01-01

    ...). High-density lipoprotein from healthy subjects (HDL(Healthy)) has been proposed to exert endothelial antiapoptotic effects that may represent an important antiatherogenic property of the lipoprotein...

  20. Path to Efficient Lower Hybrid Current Drive at High Density

    Science.gov (United States)

    Baek, S. G.; Bonoli, P. T.; Brunner, D.; Faust, I.; Labombard, B. L.; Parker, R. R.; Shiraiwa, S.; Wallace, G. M.; Wukitch, S.

    2015-11-01

    Recovery of lower hybrid current drive (LHCD) efficiency at high density was demonstrated on Alcator C-Mod by modifying the scrape-off layer (SOL) plasma. RF probe measurements around the C-Mod tokamak indicate that the LH wave amplitude at the high field side wall significantly attenuates with plasma density. This is interpreted as enhanced collisional loss due to the increase in the SOL density and width. By taking advantage of the narrower SOL width by doubling plasma current to 1.1 MA, it is found that the LH wave amplitude maintains its strength, and an effective current drive is extended to above 1x10e20 m-3. An order of magnitude increase in non-thermal Bremsstrahlung emission is consistent with ray-tracing results which take into account the change of SOL profiles with current. In the coming campaign, a further investigation on the role of the SOL plasma is planned by raising plasma current above 1.1 MA. This will be aided with newly developed RF magnetic loop antennas mounted on a radially movable probe head. This system is expected to intercept the LH resonance cone on the first pass, allowing us to measure radial profiles of both the wave amplitude and dominant parallel wavenumber in the SOL for the first time. These data will be compared with the GENRAY ray-tracing code. Work supported by USDoE awards DE-FC02-99ER54512.

  1. Patterned Platinum Etching Studies in an Argon High Density Plasma

    Science.gov (United States)

    Delprat, Sébastien; Chaker, Mohamed; Margot, Joëlle; Pépin, Henri; Tan, Liang; Smy, Tom

    1998-10-01

    A high-density surface-wave Ar plasma operated in the low pressure regime is used to study pure physical etching characteristics of platinum thin films. The platinum samples are RF biased so as to obtain a maximum DC self-bias voltage of 150 V. The sputter-etching characteristics are investigated as a function of the magnetic field intensity, the self-bias voltage and the gas pressure. At 1 mtorr, the etch rate is found to be a unique linear function of both the self-bias voltage and the ion density, independently of the magnetic field intensity value. However, even though the ion density increases, the etch rate is found to decrease with increasing pressure. In the low pressure regime, etch rates as high as 2000 A/min are obtained with a good selectivity over resist. Without any optimization of the etching process, we were able to etch 0.5 micron Pt trenches, 0.6 micron thick yielding fence-free profiles and sidewall angles (75º) that already meets the present industrial requirements of NVRAM technology.

  2. Calvarial reconstruction using high-density porous polyethylene cranial hemispheres

    Directory of Open Access Journals (Sweden)

    Nitin J Mokal

    2011-01-01

    Full Text Available Aims: Cranial vault reconstruction can be performed with a variety of autologous or alloplastic materials. We describe our experience using high-density porous polyethylene (HDPE cranial hemisphere for cosmetic and functional restoration of skull defects. The porous nature of the implant allows soft tissue ingrowth, which decreases the incidence of infection. Hence, it can be used in proximity to paranasal sinuses and where previous alloplastic cranioplasties have failed due to implant infection. Materials and Methods: We used the HDPE implant in seven patients over a three-year period for reconstruction of moderate to large cranial defects. Two patients had composite defects, which required additional soft tissue in the form of free flap and tissue expansion. Results: In our series, decompressive craniectomy following trauma was the commonest aetiology and all defects were located in the fronto-parieto-temporal region. The defect size was 10 cm on average in the largest diameter. All patients had good post-operative cranial contour and we encountered no infections, implant exposure or implant migration. Conclusions: Our results indicate that the biocompatibility and flexibility of the HDPE cranial hemisphere implant make it an excellent alternative to existing methods of calvarial reconstruction.

  3. Stability of discoidal high-density lipoprotein particles

    Science.gov (United States)

    Maleki, Mohsen; Fried, Eliot

    Motivated by experimental and numerical studies revealing that discoidal high-density lipoprotein (HDL) particles may adopt flat elliptical and nonplanar saddle-like configurations, it is hypothesized that these might represent stabilized configurations of initially unstable flat circular particles. A variational description is developed to explore the stability of a flat circular discoidal HDL particle. While the lipid bilayer is modeled as two-dimensional fluid film endowed with surface tension and bending elasticity, the apoA-I belt is modeled as one-dimensional inextensible twist-free chain endowed with bending elasticity. Stability is investigated using the second variation of the underlying energy functional. Various planar and nonplanar instability modes are predicted and corresponding nondimensional critical values of salient dimensionless parameters are obtained. The results predict that the first planar and nonplanar unstable modes occur due to in-plane elliptical and transverse saddle-like perturbations. Based on available data, detailed stability diagrams indicate the range of input parameters for which a flat circular discoidal HDL particle is linearly stable or unstable.

  4. High-density matter: current status and future challenges

    Science.gov (United States)

    Stone, J. R.

    2015-05-01

    There are many fascinating processes in the Universe which we observe in more and more in detail thanks to increasingly sophisticated technology. One of the most interesting phenomena is the life cycle of stars, their birth, evolution and death. If the stars are massive enough, they end their lives in the core-collapse supernova explosion, the one of the most violent events in the Universe. As the result, the densest objects in the Universe, neutron stars and/or black holes are created. Naturally, the physical basis of these events should be understood in line with observation. The current status of our knowledge of processes in the life of stars is far from adequate for their true understanding. We show that although many models have been constructed their detailed ability to describe observations is limited or non-existent. Furthermore the general failure of all models means that we cannot tell which are heading in the right direction. A possible way forward in modeling of high-density matter is outlined, exemplified by the quark-meson-coupling model (QMC). This model has a natural explanation for the saturation of nuclear forces and depends on very few adjustable parameters, strongly constrained by the underlying physics. Latest QMC results for compact objects and finite nuclei are presented.

  5. Properties of Raphia Palm Interspersed Fibre Filled High Density Polyethylene

    Directory of Open Access Journals (Sweden)

    Henry C. Obasi

    2013-01-01

    Full Text Available Blends of nonbiodegradable and biodegradable polymers can promote a reduction in the volume of plastic waste when they undergo partial degradation. In this study, properties of raphia palm interspersed fibre (RPIF filled high density polyethylene (HDPE have been investigated at different levels of filler loadings, 0 to 60 wt.%. Maleic anhydride-graft polyethylene was used as a compatibilizer. Raphia palm interspersed fibre was prepared by grinding and sieved to a particle size of 150 µm. HDPE blends were prepared in a corotating twin screw extruder. Results showed that the tensile strength and elongation at break of the blends decreased with increase in RPI loadings and addition of MA-g-PE was found to improve these properties. However, the Young’s modulus increased with increase in the amount of RPI into HDPE and compatibilization further increased the Young’s modulus. The water absorption indices and weight loss for RPI/HDPE composites were found to increase with RPI loadings but were decreased on addition of MA-g-PE.

  6. Anti-Viral Antibody Profiling by High Density Protein Arrays

    Science.gov (United States)

    Bian, Xiaofang; Wiktor, Peter; Kahn, Peter; Brunner, Al; Khela, Amritpal; Karthikeyan, Kailash; Barker, Kristi; Yu, Xiaobo; Magee, Mitch; Wasserfall, Clive H.; Gibson, David; Rooney, Madeleine E; Qiu, Ji; LaBaer, Joshua

    2015-01-01

    Viral infections elicit anti-viral antibodies and have been associated with various chronic diseases. Detection of these antibodies can facilitate diagnosis, treatment of infection and understanding of the mechanisms of virus associated diseases. In this work, we assayed anti-viral antibodies using a novel high density-nucleic acid programmable protein array (HD-NAPPA) platform. Individual viral proteins were expressed in situ directly from plasmids encoding proteins in an array of microscopic reaction chambers. Quality of protein display and serum response was assured by comparing intra- and inter- array correlation within or between printing batches with average correlation coefficients of 0.91 and 0.96, respectively. HD-NAPPA showed higher signal to background (S/B) ratio compared with standard NAPPA on planar glass slides and ELISA. Antibody responses to 761 antigens from 25 different viruses were profiled among patients with juvenile idiopathic arthritis (JIA) and type 1 diabetes (T1D). Common as well as unique antibody reactivity patterns were detected between patients and healthy controls. We believe HD-viral-NAPPA will enable the study of host-pathogen interactions at unprecedented dimensions and elucidate the role of pathogen infections in disease development. PMID:25758251

  7. High-density matter: current status and future challenges

    Directory of Open Access Journals (Sweden)

    Stone J. R.

    2015-01-01

    Full Text Available There are many fascinating processes in the Universe which we observe in more and more in detail thanks to increasingly sophisticated technology. One of the most interesting phenomena is the life cycle of stars, their birth, evolution and death. If the stars are massive enough, they end their lives in the core-collapse supernova explosion, the one of the most violent events in the Universe. As the result, the densest objects in the Universe, neutron stars and/or black holes are created. Naturally, the physical basis of these events should be understood in line with observation. The current status of our knowledge of processes in the life of stars is far from adequate for their true understanding. We show that although many models have been constructed their detailed ability to describe observations is limited or non-existent. Furthermore the general failure of all models means that we cannot tell which are heading in the right direction. A possible way forward in modeling of high-density matter is outlined, exemplified by the quark-meson-coupling model (QMC. This model has a natural explanation for the saturation of nuclear forces and depends on very few adjustable parameters, strongly constrained by the underlying physics. Latest QMC results for compact objects and finite nuclei are presented.

  8. Effect of substrates on crystallization of high density polyethylene

    Institute of Scientific and Technical Information of China (English)

    范毓润; 林渊; 阮绵照

    2008-01-01

    The experimental observations about remarkable influence of the substrates on the isothermal crystallization rate of a high density polyethylene(HDPE) were presented.Two methods were used to characterize the crystallization rate:the change of turbidity of the HDPE specimen and the changes of the complex viscosity and storage modulus measured by a rotational rheometer,which gave consistent results showing that the isothermal crystallization rate decreased in sequence as the specimen contacted with aluminum,brass and stainless steel plates,respectively.As to the dominant influence factor,the chemical composition of the substrates can be excluded via insulating the plate by an aluminum foil.Instead,we propose the plate’s ability of removing the latent heat of crystallization from the specimen.Rheological measurement is sensitive to the crystallization process.The colloid like model proposed by BOUTAHAR et al for the crystallization of HDPE gives reasonable predictions of the crystallized fraction from the measured storage modulus.

  9. High-density myoelectric pattern recognition toward improved stroke rehabilitation.

    Science.gov (United States)

    Zhang, Xu; Zhou, Ping

    2012-06-01

    Myoelectric pattern-recognition techniques have been developed to infer user's intention of performing different functional movements. Thus electromyogram (EMG) can be used as control signals of assisted devices for people with disabilities. Pattern-recognition-based myoelectric control systems have rarely been designed for stroke survivors. Aiming at developing such a system for improved stroke rehabilitation, this study assessed detection of the affected limb's movement intention using high-density surface EMG recording and pattern-recognition techniques. Surface EMG signals comprised of 89 channels were recorded from 12 hemiparetic stroke subjects while they tried to perform 20 different arm, hand, and finger/thumb movements involving the affected limb. A series of pattern-recognition algorithms were implemented to identify the intended tasks of each stroke subject. High classification accuracies (96.1% ± 4.3%) were achieved, indicating that substantial motor control information can be extracted from paretic muscles of stroke survivors. Such information may potentially facilitate improved stroke rehabilitation.

  10. The High Density Region of QCD from an Effective Model

    CERN Document Server

    De Pietri, R; Seiler, E; Stamatescu, I O

    2007-01-01

    We study the high density region of QCD within an effective model obtained in the frame of the hopping parameter expansion and choosing Polyakov-type loops as the main dynamical variables representing the fermionic matter. This model still shows the so-called sign problem, a difficulty peculiar to non-zero chemical potential, but it permits the development of algorithms which ensure a good overlap of the simulated Monte Carlo ensemble with the true one. We review the main features of the model and present results concerning the dependence of various observables on the chemical potential and on the temperature, in particular of the charge density and the Polykov loop susceptibility, which may be used to characterize the various phases expected at high baryonic density. In this way, we obtain information about the phase structure of the model and the corresponding phase transitions and cross over regions, which can be considered as hints about the behaviour of non-zero density QCD.

  11. Multiple parton interactions in high-density QCD matter

    CERN Document Server

    Srivastava, D K; Srivastava, Dinesh K.; Geiger, Klaus

    1999-01-01

    Multiple interactions of quarks and gluons in high-energy heavy-ion collisions may give rise to interesting phemomena of color charges propagating in high-density QCD matter. We study the dynamics of multi-parton systems produced in nucleus-nucleus collisions at energies corresponding the the CERN SPS and the future BNL RHIC experiments. Due to the complexity of the multi-particle dynamics we choose to employ the parton cascade model in order to simulate the development of multiple parton scatterings and associated stimulated emision processes. Our results indicate a non-linear increase with nuclear mass A of, e.g., parton multiplicity, energy density, strangeness, and contrast a linear A-scaling as in Glauber-type approaches. If multiple interactions are suppressed and only single parton scatterings (no re-interactions) are considered, we recover such a linear behavior. It remains to be studied whether these results on the parton level can be experimentally seen in final-state observables, such as the charge...

  12. Probucol alleviates atherosclerosis and improves high density lipoprotein function

    Directory of Open Access Journals (Sweden)

    Zhong Jian-Kai

    2011-11-01

    Full Text Available Abstract Background Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C. However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function. Methods Eighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [3H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks. Results Compared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased. Conclusion Probucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions.

  13. High density and high temperature plasmas in Large Helical Device

    Science.gov (United States)

    Komori, Akio

    2010-11-01

    Recently a new confinement regime called Super Dense Core (SDC) mode was discovered in Large Helical Device (LHD). An extremely high density core region with more than ~ 1 × 1021 m-3 is obtained with the formation of an Internal Diffusion Barrier (IDB). The density gradient at the IDB is very high and the particle confinement in the core region is ~ 0.2 s. It is expected, for the future reactor, that the IDB-SDC mode has a possibility to achieve the self-ignition condition with lower temperature than expected before. Conventional approaches to increase the temperature have also been tried in LHD. For the ion heating, the perpendicular neutral beam injection effectively increased the ion temperature up to 5.6 keV with the formation of the internal transport barrier (ITB). In the electron heating experiments with 77 GHz gyrotrons, the highest electron temperature more than 15 keV was achieved, where plasmas are in the neoclassical regime.

  14. High density and high temperature plasmas in Large Helical Device

    Energy Technology Data Exchange (ETDEWEB)

    Komori, Akio, E-mail: komori@LHD.nifs.ac.jp [National Institute for Fusion Science, 322-6 Oroshi, Toki, Gifu 509-5292 (Japan)

    2010-11-01

    Recently a new confinement regime called Super Dense Core (SDC) mode was discovered in Large Helical Device (LHD). An extremely high density core region with more than {approx} 1 x 10{sup 21} m{sup -3} is obtained with the formation of an Internal Diffusion Barrier (IDB). The density gradient at the IDB is very high and the particle confinement in the core region is {approx} 0.2 s. It is expected, for the future reactor, that the IDB-SDC mode has a possibility to achieve the self-ignition condition with lower temperature than expected before. Conventional approaches to increase the temperature have also been tried in LHD. For the ion heating, the perpendicular neutral beam injection effectively increased the ion temperature up to 5.6 keV with the formation of the internal transport barrier (ITB). In the electron heating experiments with 77 GHz gyrotrons, the highest electron temperature more than 15 keV was achieved, where plasmas are in the neoclassical regime.

  15. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    Science.gov (United States)

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  16. High-density housing that works for all

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, Arif

    2010-03-15

    In an urbanising world, the way people fit into cities is vastly important - socially, economically, environmentally, even psychologically. So density, or the number of people living in a given area, is central to urban design and planning. Both governments and markets tend to get density wrong, leading to overcrowding, urban sprawl or often both. A case in point are the high-rise buildings springing up throughtout urban Asia - perceived as key features of that widely touted concept, the 'world-class city'. While some may offer a viable solution to land pressures and density requirements, many built to house evicted or resettled 'slum' dwellers are a social and economic nightmare - inconveniently sited, overcrowded and costly. New evidence from Karachi, Pakistan, reveals a real alternative. Poor people can create liveable high-density settlements as long as community control, the right technical assistance and flexible designs are in place. A city is surely 'world-class' only when it is cosmopolitan – built to serve all, including the poorest.

  17. High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Philip J. Barter

    2013-09-01

    Full Text Available High density lipoproteins (HDLs have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic β cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

  18. High-density lipoprotein endocytosis in endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Stefanie; Fruhwürth; Margit; Pavelka; Robert; Bittman; Werner; J; Kovacs; Katharina; M; Walter; Clemens; Rhrl; Herbert; Stangl

    2013-01-01

    AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

  19. SELDI-TOF mass spectrometry of High-Density Lipoprotein

    Directory of Open Access Journals (Sweden)

    Rezaee Farhad

    2007-09-01

    Full Text Available Abstract Background High-Density Lipoprotein (HDL, one of the main plasma lipoproteins, serves as a docking station for proteins involved in inflammation, coagulation, and lipid metabolism. Methods To elucidate the protein composition of HDL, we employed SELDI-TOF mass spectrometry as a potential high-throughput proteomic candidate for protein profiling of HDL. HDL derived from normolipemic individuals was captured on PS20 protein-chips using covalently bound antibodies against apo A-I or A-II. Results After optimisation, on-chip capture of HDL particles directly from plasma or from pre-purified HDL resulted in comparable fingerprints confirming specific capture of HDL. Depending on the capture antibody some differences in the fingerprint were observed. The most detailed fingerprint was observed up to 50 kDa; approximately 95 peaks were detected in the 3–50 kDa molecular mass range. Between 50 and 160 kDa, 27 more peaks were detected. Conclusion Based on these results, SELDI-TOF MS may be a suitable high-throughput candidate for HDL protein profiling and marker search. This approach may be used to i investigate the underlying mechanisms that lead to increased atherothrombotic risk and ii to investigate the atherothrombotic state of an individual.

  20. Low fasting low high-density lipoprotein and postprandial lipemia

    Directory of Open Access Journals (Sweden)

    Sorodila Konstandina

    2004-07-01

    Full Text Available Abstract Background Low levels of high density lipoprotein (HDL cholesterol and disturbed postprandial lipemia are associated with coronary heart disease. In the present study, we evaluated the variation of triglyceride (TG postprandially in respect to serum HDL cholesterol levels. Results Fifty two Greek men were divided into 2 main groups: a the low HDL group (HDL p = 0.002. The low HDL group had significantly higher TG at 4, 6 and 8 h postprandially compared to the controls (p = 0.006, p = 0.002, and p p = 0.017 compared to the matched-control group. ROC analysis showed that fasting TG ≥ 121 mg/dl have 100% sensitivity and 81% specificity for an abnormal TG response (auc = 0.962, p Conclusions The delayed TG clearance postprandially seems to result in low HDL cholesterol even in subjects with low fasting TG. The fasting TG > 121 mg/dl are predictable for abnormal response to fatty meal.

  1. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target.

  2. High-Density Carbon (HDC) Ablator for NIC Ignition Capsules

    Science.gov (United States)

    Ho, D.; Haan, S.; Salmonson, J.; Milovich, J.; Callahan, D.

    2012-10-01

    HDC ablators show high performance based on simulations, despite the fact that the shorter pulses for HDC capsules result in higher M-band radiation compared to that for plastic capsules. HDC capsules have good 1-D performance because HDC has relatively high density (3.5 g/cc), which results in a thinner ablator that absorbs more radiation. HDC ablators have good 2-D performance because the ablator surface is more than an order-of-magnitude smoother than Be or plastic ablators. Refreeze of the ablator near the fuel region can be avoided by appropriate dopant placement. Here we present two HDC ignition designs doped with W and Si. For the design with maximum W concentration of 1.0 at% (and respectively with maximum Si concentration of 2.0 at%): peak velocity = 0.395 (0.397) mm/ns, mass weighted fuel entropy = 0.463 (0.469) kJ/mg/eV, peak core hydrodynamic stagnation pressure = 690 (780) Gbar, and yield = 17.3 (20.2) MJ. 2-D simulations show that yield is close to 80% YoC even with 2.5x of nominal surface roughness on all surfaces. The clean fuel fraction is about 75% at peak velocity. Doping HDC with the required concentration of W and Si is in progress. A first undoped HDC Symcap is scheduled to be fielded later this year.

  3. High-density lipoprotein (HDL) metabolism and bone mass.

    Science.gov (United States)

    Papachristou, Nicholaos I; Blair, Harry C; Kypreos, Kyriakos E; Papachristou, Dionysios J

    2017-05-01

    It is well appreciated that high-density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models, have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in metabolic pathways of HDL favors adipoblastic differentiation and restrains osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regard to the HDL-bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way toward the development of novel and more effective therapies against these conditions. © 2017 Society for Endocrinology.

  4. Formation of FRCs on the Pulsed High Density Experiment

    Science.gov (United States)

    Andreason, Samuel; Slough, John

    2008-11-01

    The Pulsed High Density (PHD) experiment has been reassembled at a new facility with sufficient space to continue through the full acceleration and compression stages to reach breakeven. The intention here is to produce a large FRC, but remain in the kinetic regime where the FRC is stable and the transport sufficiently low that a Q > 1 plasma can be attained at moderate densities ˜ 10^23 m-3. During reassembly a more complete analysis of previous experimental results has been made. One of the issues in the early phase of the experiment was inefficient flux trapping during field reversal due to the large scale of the FRC source (0.4 m radius). The on-axis seed plasma was unable to diffuse out to the walls on a timescale commensurate with the introduction of bias fields. This resulted in more than half of the initial bias flux lost before sheath formation halted flux loss. An annular array of plasma sources has been constructed that solves this problem and greatly enhances the flux retention. Dynamic formation has been employed on PHD and analysis tools capable of interpreting the magnetic loop diagnostic array have been developed. Results with comparison to numerical models will be presented.

  5. Iatrogenic severe depression of high-density lipoprotein cholesterol.

    Science.gov (United States)

    Mymin, D; Dembinski, T; Friesen, M H

    2009-07-01

    The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol.

  6. Properties of recycled high density polyethylene and coffee dregs composites

    Directory of Open Access Journals (Sweden)

    Sibele Piedade Cestari

    2013-01-01

    Full Text Available Composites of recycled high density polyethylene (HDPE-R and coffee dregs (COFD were elaborated. The blends were made at the proportions of 100-0, 90-10, 80-20, 70-30, 60-40, 50-50 and 40-60% polymer-filler ratio. The materials were evaluated through scanning electron microscopy (SEM, differential scanning calorimetry (DSC, thermogravimetry/derivative thermogravimetry (TGA, and compressive resistance test. The compounding was done using a two-stage co-kneader system extruder, and then cylindrical specimens were injection molded. All composites had a fine dispersion of the COFD into the polymeric matrix. The composites degraded in two steps. The first one was in a temperature lower than the neat HDPE, but higher than the average processing temperature of the polymer. The melting temperature and the degree of crystallinity of the composites resulted similar to the neat HDPE ones. The compressive moduli of the composites resulted similar to the neat polymer one. The results show that these composites have interesting properties as a building material.

  7. OLEOPHOBIC AND HYDROPHOBIC FEATURE EXPERIMENTS OF FLUORINATED HIGH DENSITY POLYETHYLENE

    Institute of Scientific and Technical Information of China (English)

    杨宏伟; 魏贤勇; 费逸伟; 孙世安; 李晓越

    2013-01-01

    The surface performances of directly fluorinated high density polyethylene (HDPE) are studied with Fourier transform infrared (FT-IR) spectra ,scanning electron microscopy (SEM) and contact angle (CA) system . The SEM images show that there is a three-layer structure called the reaction ,virgin and boundary layer structure . The depth of fluorinated layer is 5.75 μm with 1 h fluorination time and 7.86 μm with 2 h . The depths are 5.46 μm and 5.07 μm when fluorine density is 2% and 1% ,respectively .CA indicates that the HDPE surface property becomes more hydrophobic with the increasing water contact angle from 78.5° to 104.5° .Oleophobic and hydrophobic features of HDPE are identified by comparison of mass change experiments .It is shown that the in-crement rate of fluorinated HDPE is much lower than that of un-fluorinated HDPE filled in neither distilled water nor jet fuel .

  8. High-Density Infrared Surface Treatments of Refractories

    Energy Technology Data Exchange (ETDEWEB)

    Tiegs, T.N.

    2005-03-31

    Refractory materials play a crucial role in all energy-intensive industries and are truly a crosscutting technology for the Industries of the Future (IOF). One of the major mechanisms for the degradation of refractories and a general decrease in their performance has been the penetration and corrosion by molten metals or glass. Methods and materials that would reduce the penetration, wetting, and corrosive chemistry would significantly improve refractory performance and also maintain the quality of the processed liquid, be it metal or glass. This report presents the results of an R&D project aimed at investigating the use of high-density infrared (HDI) heating to surface treat refractories to improve their performance. The project was a joint effort between Oak Ridge National Laboratory (ORNL) and the University of Missouri-Rolla (UMR). HDI is capable of heating the near-surface region of materials to very high temperatures where sintering, diffusion, and melting can occur. The intended benefits of HDI processing of refractories were to (1) reduce surface porosity (by essentially sealing the surface to prevent liquid penetration), (2) allow surface chemistry changes to be performed by bonding an adherent coating onto the underlying refractory (in order to inhibit wetting and/or improve corrosion resistance), and (3) produce noncontact refractories with high-emissivity surface coatings.

  9. A system verification platform for high-density epiretinal prostheses.

    Science.gov (United States)

    Chen, Kuanfu; Lo, Yi-Kai; Yang, Zhi; Weiland, James D; Humayun, Mark S; Liu, Wentai

    2013-06-01

    Retinal prostheses have restored light perception to people worldwide who have poor or no vision as a consequence of retinal degeneration. To advance the quality of visual stimulation for retinal implant recipients, a higher number of stimulation channels is expected in the next generation retinal prostheses, which poses a great challenge to system design and verification. This paper presents a system verification platform dedicated to the development of retinal prostheses. The system includes primary processing, dual-band power and data telemetry, a high-density stimulator array, and two methods for output verification. End-to-end system validation and individual functional block characterization can be achieved with this platform through visual inspection and software analysis. Custom-built software running on the computers also provides a good way for testing new features before they are realized by the ICs. Real-time visual feedbacks through the video displays make it easy to monitor and debug the system. The characterization of the wireless telemetry and the demonstration of the visual display are reported in this paper using a 256-channel retinal prosthetic IC as an example.

  10. Experimental study of high density foods for the Space Operations Center

    Science.gov (United States)

    Ahmed, S. M.

    1981-01-01

    The experimental study of high density foods for the Space Operations Center is described. A sensory evaluation of the high density foods was conducted first to test the acceptability of the products. A shelf-life study of the high density foods was also conducted for three different time lengths at three different temperatures. The nutritional analysis of the high density foods is at present incomplete.

  11. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Directory of Open Access Journals (Sweden)

    Kuroda S

    2014-08-01

    Full Text Available Shinji Kuroda,1 Justina Tam,2 Jack A Roth,1 Konstantin Sokolov,2 Rajagopal Ramesh3–5 1Department of Thoracic and Cardiovascular Surgery, 2Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Pathology, 4Graduate Program in Biomedical Sciences, 5Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Background: We have previously demonstrated the epidermal growth factor receptor (EGFR-targeted hybrid plasmonic magnetic nanoparticles (225-NP produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods: The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results: The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the

  12. High-density lipoprotein proteome dynamics in human endotoxemia

    Directory of Open Access Journals (Sweden)

    Stroes Erik SG

    2011-06-01

    Full Text Available Abstract Background A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L and 10 men with high HDL cholesterol levels (1.9+/-0.4 mmol/L were challenged with endotoxin (LPS intravenously (1 ng/kg bodyweight. We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome. Results Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value Conclusions This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.

  13. Differential analysis for high density tiling microarray data

    Directory of Open Access Journals (Sweden)

    Kapranov Philipp

    2007-09-01

    Full Text Available Abstract Background High density oligonucleotide tiling arrays are an effective and powerful platform for conducting unbiased genome-wide studies. The ab initio probe selection method employed in tiling arrays is unbiased, and thus ensures consistent sampling across coding and non-coding regions of the genome. These arrays are being increasingly used to study the associated processes of transcription, transcription factor binding, chromatin structure and their association. Studies of differential expression and/or regulation provide critical insight into the mechanics of transcription and regulation that occurs during the developmental program of a cell. The time-course experiment, which comprises an in-vivo system and the proposed analyses, is used to determine if annotated and un-annotated portions of genome manifest coordinated differential response to the induced developmental program. Results We have proposed a novel approach, based on a piece-wise function – to analyze genome-wide differential response. This enables segmentation of the response based on protein-coding and non-coding regions; for genes the methodology also partitions differential response with a 5' versus 3' versus intra-genic bias. Conclusion The algorithm built upon the framework of Significance Analysis of Microarrays, uses a generalized logic to define regions/patterns of coordinated differential change. By not adhering to the gene-centric paradigm, discordant differential expression patterns between exons and introns have been identified at a FDR of less than 12 percent. A co-localization of differential binding between RNA Polymerase II and tetra-acetylated histone has been quantified at a p-value -13. The prototype R code has been made available as supplementary material [see Additional file 1]. Additional file 1 gsam_prototypercode.zip. File archive comprising of prototype R code for gSAM implementation including readme and examples. Click here for file

  14. Differential analysis for high density tiling microarray data.

    Science.gov (United States)

    Ghosh, Srinka; Hirsch, Heather A; Sekinger, Edward A; Kapranov, Philipp; Struhl, Kevin; Gingeras, Thomas R

    2007-09-24

    High density oligonucleotide tiling arrays are an effective and powerful platform for conducting unbiased genome-wide studies. The ab initio probe selection method employed in tiling arrays is unbiased, and thus ensures consistent sampling across coding and non-coding regions of the genome. These arrays are being increasingly used to study the associated processes of transcription, transcription factor binding, chromatin structure and their association. Studies of differential expression and/or regulation provide critical insight into the mechanics of transcription and regulation that occurs during the developmental program of a cell. The time-course experiment, which comprises an in-vivo system and the proposed analyses, is used to determine if annotated and un-annotated portions of genome manifest coordinated differential response to the induced developmental program. We have proposed a novel approach, based on a piece-wise function - to analyze genome-wide differential response. This enables segmentation of the response based on protein-coding and non-coding regions; for genes the methodology also partitions differential response with a 5' versus 3' versus intra-genic bias. The algorithm built upon the framework of Significance Analysis of Microarrays, uses a generalized logic to define regions/patterns of coordinated differential change. By not adhering to the gene-centric paradigm, discordant differential expression patterns between exons and introns have been identified at a FDR of less than 12 percent. A co-localization of differential binding between RNA Polymerase II and tetra-acetylated histone has been quantified at a p-value < 0.003; it is most significant at the 5' end of genes, at a p-value < 10-13. The prototype R code has been made available as supplementary material [see Additional file 1].

  15. Surface interactions involved in flashover with high density electronegative gases.

    Energy Technology Data Exchange (ETDEWEB)

    Hodge, Keith Conquest; Warne, Larry Kevin; Jorgenson, Roy Eberhardt; Wallace, Zachariah Red; Lehr, Jane Marie

    2010-01-01

    This report examines the interactions involved with flashover along a surface in high density electronegative gases. The focus is on fast ionization processes rather than the later time ionic drift or thermalization of the discharge. A kinetic simulation of the gas and surface is used to examine electron multiplication and includes gas collision, excitation and ionization, and attachment processes, gas photoionization and surface photoemission processes, as well as surface attachment. These rates are then used in a 1.5D fluid ionization wave (streamer) model to study streamer propagation with and without the surface in air and in SF6. The 1.5D model therefore includes rates for all these processes. To get a better estimate for the behavior of the radius we have studied radial expansion of the streamer in air and in SF6. The focus of the modeling is on voltage and field level changes (with and without a surface) rather than secondary effects, such as, velocities or changes in discharge path. An experiment has been set up to carry out measurements of threshold voltages, streamer velocities, and other discharge characteristics. This setup includes both electrical and photographic diagnostics (streak and framing cameras). We have observed little change in critical field levels (where avalanche multiplication sets in) in the gas alone versus with the surface. Comparisons between model calculations and experimental measurements are in agreement with this. We have examined streamer sustaining fields (field which maintains ionization wave propagation) in the gas and on the surface. Agreement of the gas levels with available literature is good and agreement between experiment and calculation is good also. Model calculations do not indicate much difference between the gas alone versus the surface levels. Experiments have identified differences in velocity between streamers on the surface and in the gas alone (the surface values being larger).

  16. High-density lipoprotein and atherosclerosis: Roles of lipid transporters

    Institute of Scientific and Technical Information of China (English)

    Yoshinari; Uehara; Keijiro; Saku

    2014-01-01

    Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

  17. High density 3D printed microfluidic valves, pumps, and multiplexers.

    Science.gov (United States)

    Gong, Hua; Woolley, Adam T; Nordin, Gregory P

    2016-07-07

    In this paper we demonstrate that 3D printing with a digital light processor stereolithographic (DLP-SLA) 3D printer can be used to create high density microfluidic devices with active components such as valves and pumps. Leveraging our previous work on optical formulation of inexpensive resins (RSC Adv., 2015, 5, 106621), we demonstrate valves with only 10% of the volume of our original 3D printed valves (Biomicrofluidics, 2015, 9, 016501), which were already the smallest that have been reported. Moreover, we show that incorporation of a thermal initiator in the resin formulation along with a post-print bake can dramatically improve the durability of 3D printed valves up to 1 million actuations. Using two valves and a valve-like displacement chamber (DC), we also create compact 3D printed pumps. With 5-phase actuation and a 15 ms phase interval, we obtain pump flow rates as high as 40 μL min(-1). We also characterize maximum pump back pressure (i.e., maximum pressure the pump can work against), maximum flow rate (flow rate when there is zero back pressure), and flow rate as a function of the height of the pump outlet. We further demonstrate combining 5 valves and one DC to create a 3-to-2 multiplexer with integrated pump. In addition to serial multiplexing, we also show that the device can operate as a mixer. Importantly, we illustrate the rapid fabrication and test cycles that 3D printing makes possible by implementing a new multiplexer design to improve mixing, and fabricate and test it within one day.

  18. Ultra-high Density SNParray in Neuroblastoma Molecular Diagnostics

    Directory of Open Access Journals (Sweden)

    Inge M. Ambros

    2014-08-01

    Full Text Available Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e. amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses: so called segmental chromosomal aberrations, i.e. gains or losses of chromosomal fragments, can also indicate tumor aggressiveness. The clinical use of these genomic aberrations has, however, been hampered for many years by methodical and interpretational problems. Only after reaching worldwide consensus on markers, methodology, and data interpretation, information on SCAs has recently been implemented in clinical studies. Now, a number of collaborative studies within COG, GPOH and SIOPEN use genomic information to stratify therapy for patients with localized and metastatic disease. Recently, new types of DNA based aberrations influencing the clinical behavior of neuroblastomas have been described. Deletions or mutations of genes like ATRX and a phenomenon referred to as chromothripsis are all assumed to correlate with an unfavorable clinical behavior. However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques. Single nucleotide polymorphism (SNP arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine. Here, we present an ultra-high density (UHD SNParray technique which is, because of its high specificity and sensitivity and the combined copy number and allele information, highly appropriate for the genomic diagnosis of neuroblastoma and other malignancies.

  19. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Science.gov (United States)

    Kuroda, Shinji; Tam, Justina; Roth, Jack A; Sokolov, Konstantin; Ramesh, Rajagopal

    2014-01-01

    Background We have previously demonstrated the epidermal growth factor receptor (EGFR)-targeted hybrid plasmonic magnetic nanoparticles (225-NP) produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. Conclusion The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth

  20. β-Arrestin1/miR-326 Transcription Unit Is Epigenetically Regulated in Neural Stem Cells Where It Controls Stemness and Growth Arrest

    Science.gov (United States)

    Begalli, Federica; Abballe, Luana; Catanzaro, Giuseppina; Vacca, Alessandra; Napolitano, Maddalena; Tafani, Marco; Giangaspero, Felice; Locatelli, Franco

    2017-01-01

    Cell development is regulated by a complex network of mRNA-encoded proteins and microRNAs, all funnelling onto the modulation of self-renewal or differentiation genes. How intragenic microRNAs and their host genes are transcriptionally coregulated and their functional relationships for the control of neural stem cells (NSCs) are poorly understood. We propose here the intragenic miR-326 and its host gene β-arrestin1 as novel players whose epigenetic silencing maintains stemness in normal cerebellar stem cells. Such a regulation is mediated by CpG islands methylation of the common promoter. Epigenetic derepression of β-arrestin1/miR-326 by differentiation signals or demethylating agents leads to suppression of stemness features and cell growth and promotes cell differentiation. β-Arrestin1 inhibits cell proliferation by enhancing the nuclear expression of the cyclin-dependent kinase inhibitor p27. Therefore, we propose a new mechanism for the control of cerebellar NSCs where a coordinated epigenetic mechanism finely regulates β-arrestin1/miR-326 expression and consequently NSCs stemness and cell growth. PMID:28298929

  1. Theracurmin® efficiently inhibits the growth of human prostate and bladder cancer cells via induction of apoptotic cell death and cell cycle arrest.

    Science.gov (United States)

    Kang, Minyong; Ho, Jin-Nyoung; Kook, Ha Rim; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2016-03-01

    In the present study, we aimed to investigate the anticancer properties of Theracurmin®, a novel form of the yellow curry pigment curcumin, as well as explore the molecular mechanisms of the potential anticancer effects of Theracurmin® on human prostate cancer and bladder cancer cells in vitro. The proliferation of cancer cells was examined by using the Cell Counting Kit-8. The clonogenic growth potential was determined by clonogenic assay. Cell cycle distribution was evaluated by flow cytometry using propidium iodide staining. Western blot analysis was applied to explore the expression patterns of molecules associated with apoptotic cell death and cell cycle checkpoint. We noted that Theracurmin® and curcumin exhibited similar anticancer effects in both androgen-dependent and -independent human prostate cancer cells in a dose- and time-dependent manner. These agents reduced cell viability and clonogenic growth potential by inducing apoptosis and cell cycle disturbance in human prostate cancer cells. Theracurmin® and curcumin also exerted marked anticancer effects on human bladder cancer cells, even in cisplatin-resistant T24R2 cells, in a dose- and time-dependent manner. Moreover, Theracurmin® and curcumin treatment decreased cell viability and clonogenicity via induction of apoptotic cell death and cell cycle dysregulation in human bladder cancer cells. In conclusion, our study suggests that Theracurmin® has potential as an anticancer agent in complementary and alternative medicine for these urological cancers.

  2. RhoA/phosphatidylinositol 3-kinase/protein kinase B/mitogen-activated protein kinase signaling after growth arrest-specific protein 6/mer receptor tyrosine kinase engagement promotes epithelial cell growth and wound repair via upregulation of hepatocyte growth factor in macrophages.

    Science.gov (United States)

    Lee, Ye-Ji; Park, Hyun-Jung; Woo, So-Youn; Park, Eun-Mi; Kang, Jihee Lee

    2014-09-01

    Growth arrest-specific protein 6 (Gas6)/Mer receptor tyrosine kinase (Mer) signaling modulates cytokine secretion and helps to regulate the immune response and apoptotic cell clearance. Signaling pathways that activate an epithelial growth program in macrophages are still poorly defined. We report that Gas6/Mer/RhoA signaling can induce the production of epithelial growth factor hepatic growth factor (HGF) in macrophages, which ultimately promotes epithelial cell proliferation and wound repair. The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal-regulated protein kinase, and Jun NH2-terminal kinase axis in RAW 264.7 cells, was identified as Gas6/Mer downstream signaling pathway for the upregulation of HGF mRNA and protein. Conditioned medium from RAW 264.7 cells that had been exposed to Gas6 or apoptotic cells enhanced epithelial cell proliferation of the epithelial cell line LA-4 and wound closure. Cotreatment with an HGF receptor-blocking antibody or c-Met antagonist downregulated this enhancement. Inhibition of Mer with small interfering RNA (siRNA) or the RhoA/Rho kinase pathway by RhoA siRNA or Rho kinase pharmacologic inhibitor suppressed Gas6-induced HGF mRNA and protein expression in macrophages and blocked epithelial cell proliferation and wound closure induced by the conditioned medium. Our data provide evidence that macrophages can be reprogrammed by Gas6 to promote epithelial proliferation and wound repair via HGF, which is induced by the Mer/RhoA/Akt/MAP kinase pathway. Thus, defects in Gas6/Mer/RhoA signaling in macrophages may delay tissue repair after injury to the alveolar epithelium.

  3. A high density two-dimensional electron gas in an oxide heterostructure on Si (001

    Directory of Open Access Journals (Sweden)

    E. N. Jin

    2014-11-01

    Full Text Available We present the growth and characterization of layered heterostructures comprised of LaTiO3 and SrTiO3 epitaxially grown on Si (001. Magnetotransport measurements show that the sheet carrier densities of the heterostructures scale with the number of LaTiO3/SrTiO3 interfaces, consistent with the presence of an interfacial 2-dimensional electron gas (2DEG at each interface. Sheet carrier densities of 8.9 × 1014 cm−2 per interface are observed. Integration of such high density oxide 2DEGs on silicon provides a bridge between the exceptional properties and functionalities of oxide 2DEGs and microelectronic technologies.

  4. High-Density Plasma Reactors: Simulations for Design

    Science.gov (United States)

    Hash, David B.; Meyyappan, Meyya; Arnold, James O. (Technical Monitor)

    1998-01-01

    The development of improved and more efficient plasma reactors is a costly process for the semiconductor industry. Until five years ago, the Industry made most of its advancements through a trial and error approach. More recently, the role of computational modeling in the design process has increased. Both conventional computational fluid dynamics (CFD) techniques like Navier-Stokes solvers as well as particle simulation methods are used to model plasma reactor flowfields. However, since high-density plasma reactors generally operate at low gas pressures on the order of 1 to 10 mTorr, a particle simulation may be necessary because of the failure of CFD techniques to model rarefaction effects. The direct simulation Monte Carlo method is the most widely accepted and employed particle simulation tool and has previously been used to investigate plasma reactor flowfields. A plasma DSMC code is currently under development at NASA Ames Research Center with its foundation as the object-oriented parallel Cornell DSMC code, MONACO. The present investigation is a follow up of a neutral flow investigation of the effects of process parameters as well as reactor design on etch rate and etch rate uniformity. The previous work concentrated on silicon etch of a chlorine flow in a configuration typical of electron cyclotron resonance (ECR) or helical resonator type reactors. The effects of the plasma on the dissociation chemistry were modeled by making assumptions about the electron temperature and number density. The electrons or ions themselves were not simulated.The present work extends these results by simulating the charged species.The electromagnetic fields are calculated such that power deposition is modeled self-consistently. Electron impact reactions are modeled along with mechanisms for charge exchange. An bipolar diffusion assumption is made whereby electrons remain tied to the ions. However, the velocities of tile electrons are allowed to be modified during collisions

  5. Biofuels Barrier Properties of Polyamide 6 and High Density Polyethylene

    Directory of Open Access Journals (Sweden)

    Fillot L.-A.

    2015-02-01

    Full Text Available In this paper, a comparison of the biofuels barrier properties of PolyAmide 6 (PA6 and High Density PolyEthylene (HDPE is presented. Model fuels were prepared as mixtures of toluene, isooctane and ethanol, the ethanol volume fraction varying between 0% and 100%. Barrier properties were determined at 40°C by gravimetric techniques or gas chromatography measurements, and it was shown that polyamide 6 permeability is lower than that of polyethylene on a wide range of ethanol contents up to 85% of ethanol (E85 in the biofuel, permeability of PA6 being 100 times lower than that of HDPE for low ethanol content fuels (E5, E0. The time-lags were also compared, and on the whole range of ethanol contents, HDPE permeation kinetics appears to be much faster than that of PA6, the time lag for a 1 mm thick specimens in presence of E10 being 50 days for PA6 and 0.5 days for HDPE. The compositions of the solvent fluxes were analyzed by FID gas chromatography, and it turned out that the solvent flux was mainly made up of ethanol (minimum 95% in the case of PA6, whereas in the case of HDPE, solvent flux was mainly made up of hydrocarbons. The implication of this difference in the solvent flux composition is discussed in the present article, and a side effect called the “fuel exhaustion process” is presented. The influence of the sample thickness was then studied, and for the different biofuels compositions, the pervaporation kinetics of polyamide 6 appeared to evolve with the square of the thickness, a long transitory regime being highlighted in the case of PA6. This result implies that the time needed to characterize the steady state permeability of thick PA6 parts such as fuel tanks can be very long (one year or more, this duration being far superior to the Euros 5 or Euro 6 standard emission measurements time scale. The influence of temperature on the permeability was finally assessed, and the activation energy that is the signature of the temperature

  6. Human endothelial progenitor cells internalize high-density lipoprotein.

    Science.gov (United States)

    Srisen, Kaemisa; Röhrl, Clemens; Meisslitzer-Ruppitsch, Claudia; Ranftler, Carmen; Ellinger, Adolf; Pavelka, Margit; Neumüller, Josef

    2013-01-01

    Endothelial progenitor cells (EPCs) originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL), and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate), cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal intraellular

  7. Human endothelial progenitor cells internalize high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Kaemisa Srisen

    Full Text Available Endothelial progenitor cells (EPCs originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL, and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate, cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal

  8. Hydrogen peroxide inhibits transforming growth factor-β1-induced cell cycle arrest by promoting Smad3 linker phosphorylation through activation of Akt-ERK1/2-linked signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jiyeon; Park, Seong Ji; Jo, Eun Ji [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Hui-Young [Department of Internal Medicine, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Hong, Suntaek [Laboratory of Cancer Cell Biology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840 (Korea, Republic of); Kim, Seong-Jin [CHA Cancer Institute, CHA University of Medicine and Science, Seoul 135-081 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-06-14

    Highlights: •H{sub 2}O{sub 2} inhibits TGF-β1-induced cell cycle arrest. •H{sub 2}O{sub 2} induces Smad3 linker phosphorylation through Akt-ERK1/2 pathway. •H{sub 2}O{sub 2}-mediated suppression of TGF-β signal requires Smad3 linker phosphorylation. •This is a first report about interplay between H{sub 2}O{sub 2} and growth inhibition pathway. -- Abstract: Hydrogen peroxide (H{sub 2}O{sub 2}) functions as a second messenger in growth factor receptor-mediated intracellular signaling cascade and is tumorigenic by virtue of its ability to promote cell proliferation; however, the mechanisms underlying the growth stimulatory action of H{sub 2}O{sub 2} are less understood. Here we report an important mechanism for antagonistic effects of H{sub 2}O{sub 2} on growth inhibitory response to transforming growth factor-β1 (TGF-β1). In Mv1Lu and HepG2 cells, pretreatment of H{sub 2}O{sub 2} (0.05–0.2 mM) completely blocked TGF-β1-mediated induction of p15{sup INK4B} expression and increase of its promoter activity. Interestingly, H{sub 2}O{sub 2} selectively suppressed the transcriptional activation potential of Smad3, not Smad2, in the absence of effects on TGF-β1-induced phosphorylation of the COOH-tail SSXS motif of Smad3 and its nuclear translocation. Mechanism studies showed that H{sub 2}O{sub 2} increases the phosphorylation of Smad3 at the middle linker region in a concentration- and time-dependent manner and this effect is mediated by activation of extracellular signal-activated kinase 1/2 through Akt. Furthermore, expression of a mutant Smad3 in which linker phosphorylation sites were ablated significantly abrogated the inhibitory effects of H{sub 2}O{sub 2} on TGF-β1-induced increase of p15{sup INK4B}-Luc reporter activity and blockade of cell cycle progression from G1 to S phase. These findings for the first time define H{sub 2}O{sub 2} as a signaling molecule that modulate Smad3 linker phosphorylation and its transcriptional activity, thus providing

  9. High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Jay W.; Stouffer, Richard L.; Rodland, Karin D.

    2005-06-09

    Ovarian cancer is the most lethal gynecological cancer affecting women. Hormone-based therapies are variably successful in treating ovarian cancer, but the reasoning behind these therapies is paradoxical. Clinical reagents such as tamoxifen are considered to inhibit or reverse tumor growth by competitive inhibition of the estrogen receptor (ER); however high dose estrogen is as clinically effective as tamoxifen, and it is unlikely that estrogen is acting by blocking ER activity; however, it may be activating a unique function of the ER that is nonmitogenic. For poorly defined reasons, 90% of varian cancers derive from the ovarian surface epithelium (OSE). In vivo the ER-positive OSE is exposed to high estrogen levels, reaching micromolar concentrations in dominant ovarian follicles. Using cultured OSE cells in vitro, we show that these levels of estradiol (1 ug/ml; {approx}3um) block the actions of serum growth factors, activate the G1 phase retinoblastoma AQ:A checkpoint, and induce p21, an inhibitor of kinases that normally inactivate the retinoblastoma checkpoint. We also show that estradiol increases p53 levels, which may contribute to p21 induction. Supporting the hypothesis that clinical selective ER modulators activate this novel ER function, we find that micromolar doses of tamoxifen and the ''pure antiestrogen'' ICI 182,780 elicit the same effects as estradiol. We propose that, in the context of proliferation, these data clarify some paradoxical aspects of hormone-based therapy and suggest that fuller understanding of normal ER function is necessary to improve therapeutic strategies that target the ER. (J Clin Endocrinol Metab 90: 0000-0000, 2005)

  10. Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells.

    Science.gov (United States)

    McNaughton, Melissa; Pitman, Melissa; Pitson, Stuart M; Pyne, Nigel J; Pyne, Susan

    2016-03-29

    Sphingosine kinases (two isoforms termed SK1 and SK2) catalyse the formation of the bioactive lipid sphingosine 1-phosphate. We demonstrate here that the SK2 inhibitor, ABC294640 (3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide) or the SK1/SK2 inhibitor, SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole)) induce the proteasomal degradation of SK1a (Mr = 42 kDa) and inhibit DNA synthesis in androgen-independent LNCaP-AI prostate cancer cells. These effects are recapitulated by the dihydroceramide desaturase (Des1) inhibitor, fenretinide. Moreover, SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 (Mr = 38 kDa) in LNCaP-AI prostate cancer cells. Furthermore, SKi or ABC294640 or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 failed to increase p53 and p21 expression, but the former did reduce DNA synthesis in LNCaP-AI prostate cancer cells. Moreover, N-acetylcysteine (reactive oxygen species scavenger) blocked the SK inhibitor-induced increase in p21 and p53 expression but had no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increased p53 expression while a combination of Des1/SK1 siRNA increased the expression of p21. Therefore, Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways. Therefore, we propose targeting androgen-independent prostate cancer cells with compounds that affect Des1/SK1 to modulate both de novo and sphingolipid rheostat pathways in order to induce growth arrest.

  11. ECPR for Refractory Out-Of-Hospital Cardiac Arrest

    Science.gov (United States)

    2017-05-17

    Cardiac Arrest; Heart Arrest; Sudden Cardiac Arrest; Cardiopulmonary Arrest; Death, Sudden, Cardiac; Cardiopulmonary Resuscitation; CPR; Extracorporeal Cardiopulmonary Resuscitation; Extracorporeal Membrane Oxygenation

  12. Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G2/M arrest and apoptosis

    Science.gov (United States)

    Li, Jixia; Zhu, Feng; Lubet, Ronald A.; De Luca, Antonella; Grubbs, Clinton; Ericson, Marna E.; D’Alessio, Amelia; Normano, Nicola; Dong, Zigang; Bode, Ann M.

    2012-01-01

    Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin-3-methyl ether caused in a significant growth inhibition of lapatinib-sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or ERKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G2/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and -resistant cells. In contrast, lapatinib produced an accumulation of cells in the G1 phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7 and poly (ADP-ribose) polymerase (PARP) in both cell lines. Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. PMID:22086611

  13. The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth of Erwinia amylovora and acts as a seed germination-arrest factor.

    Science.gov (United States)

    Lee, Xiaoyun; Azevedo, Mark D; Armstrong, Donald J; Banowetz, Gary M; Reimmann, Cornelia

    2013-02-01

    The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB) shares biological activities with 4-formylaminooxyvinylglycine, a related molecule produced by Pseudomonas fluorescens WH6. We found that culture filtrates of a P. aeruginosa strain overproducing AMB weakly interfered with seed germination of the grassy weed Poa annua and strongly inhibited growth of Erwinia amylovora, the causal agent of the devastating orchard crop disease known as fire blight. AMB was active against a 4-formylaminooxyvinylglycine-resistant isolate of E. amylovora, suggesting that the molecular targets of the two oxyvinylglycines in Erwinia do not, or not entirely, overlap. The AMB biosynthesis and transport genes were shown to be organized in two separate transcriptional units, ambA and ambBCDE, which were successfully expressed from IPTG-inducible tac promoters in the heterologous host P. fluorescens CHA0. Engineered AMB production enabled this model biocontrol strain to become inhibitory against E. amylovora and to weakly interfere with the germination of several graminaceous seeds. We conclude that AMB production requires no additional genes besides ambABCDE and we speculate that their expression in marketed fire blight biocontrol strains could potentially contribute to disease control.

  14. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

    Science.gov (United States)

    Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

    2010-09-01

    The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications.

  15. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  16. Strongly interacting matter at high densities with a soliton model

    Science.gov (United States)

    Johnson, Charles Webster

    1998-12-01

    One of the major goals of modern nuclear physics is to explore the phase diagram of strongly interacting matter. The study of these 'extreme' conditions is the primary motivation for the construction of the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory which will accelerate nuclei to a center of mass (c.m.) energy of about 200 GeV/nucleon. From a theoretical perspective, a test of quantum chromodynamics (QCD) requires the expansion of the conditions examined from one phase point to the entire phase diagram of strongly-interacting matter. In the present work we focus attention on what happens when the density is increased, at low excitation energies. Experimental results from the Brookhaven Alternating Gradient Synchrotron (AGS) indicate that this regime may be tested in the 'full stopping' (maximum energy deposition) scenario achieved at the AGS having a c.m. collision energy of about 2.5 GeV/nucleon for two equal- mass heavy nuclei. Since the solution of QCD on nuclear length-scales is computationally prohibitive even on today's most powerful computers, progress in the theoretical description of high densities has come through the application of models incorporating some of the essential features of the full theory. The simplest such model is the MIT bag model. We use a significantly more sophisticated model, a nonlocal confining soliton model developed in part at Kent. This model has proven its value in the calculation of the properties of individual mesons and nucleons. In the present application, the many-soliton problem is addressed with the same model. We describe nuclear matter as a lattice of solitons and apply the Wigner-Seitz approximation to the lattice. This means that we consider spherical cells with one soliton centered in each, corresponding to the average properties of the lattice. The average density is then varied by changing the size of the Wigner-Seitz cell. To arrive at a solution, we need to solve a coupled set of

  17. Ultrafine grained high density manganese zinc ferrite produced using polyol process assisted by Spark Plasma Sintering

    Energy Technology Data Exchange (ETDEWEB)

    Gaudisson, T.; Beji, Z.; Herbst, F.; Nowak, S. [ITODYS, Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR-7086, 75205 Paris (France); Ammar, S., E-mail: ammarmer@univ-paris-diderot.fr [ITODYS, Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR-7086, 75205 Paris (France); Valenzuela, R. [D2MC, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, 04510 Ciudad de Mexico (Mexico)

    2015-08-01

    We report the synthesis of Mn–Zn ferrite (MZFO) nanoparticles (NPs) by the polyol process and their consolidation by Spark Plasma Sintering (SPS) technique at relatively low temperature and short time, namely 500 °C for 10 min. NPs were obtained as perfectly epitaxied aggregated nanoclusters forming a kind of spherical pseudo-single-crystals of about 40 nm in size. The results on NPs consolidation by SPS underlined the importance of this clustering on the grain growth mechanism. Grain growth proceeds by coalescing nanocrystalline aggregates into single grain of almost the same average size, thus leading to a high density ceramic. Due to magnetic exchange interactions between grains, the produced ceramic does not exhibit thermal relaxation whereas their precursor polyol-made NPs are superparamagnetic. - Highlights: • Textured Mn–Zn ferrite nano-aggregates were produced in polyol. • Dense ceramic was obtained by SPS starting from these particles at 500 °C for 10 min. • The grain growth was driven by coalescence leading to nanometer-sized grains. • The 300 K-magnetic properties of the ceramic are typical of a soft magnet. • Its magnetization is very close to that of bulk despite its ultrafine grain size.

  18. A PROPOSAL OF NITROGEN BALANCE IN A VERY HIGH DENSITY OLIVE ORCHARD.

    Directory of Open Access Journals (Sweden)

    H. Belguerri

    2016-05-01

    Full Text Available The nitrogen (N balance was estimated in a very high density olive orchard in north- east of Spain, in order to calculate the inputs and outputs of N related to tree response and soil nitrogen availability. The calculate N inputs and outputs showed that N exported by yield and pruning material were higher for fertilized plots than unfertilized ones, and no significant differences were recorded for nitrogen mineralization between both treatments. N balance, defined as the difference between inorganic N content in soil at the end and the beginning of each year, was positive for both treatments but when vegetative growth and olive yield were compared, fertilized plots showed  higher values, So it is wrong noting that a positive N balance in both case means that olive tree will provide a peak yield and vegetative growth but  it is an adaptation of  the olive trees to different soil N availability conditions by equilibrating their vegetative growth and fruit yield.   

  19. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest.

    Science.gov (United States)

    Chiao, Jen Wei; Wu, Hongyan; Ramaswamy, Gita; Conaway, C Clifford; Chung, Fung-Lung; Wang, Longgui; Liu, Delong

    2004-08-01

    Epidemiological surveys indicate that intake of cruciferous vegetables is inversely related to prostate cancer incidence, although the responsible dietary factors have not been identified. Our studies demonstrated that exposure of human prostate cancer cells in culture to the N-acetylcysteine (NAC) conjugate of phenethyl isothiocyanate (PEITC-NAC), the major metabolite of PEITC that is abundant in watercress, inhibited proliferation and tumorigenesis. The PEITC-NAC is known to mediate cytoprotection at initiation of carcinogenesis. The relevance of PEITC-NAC in diets on the growth of prostate tumor cells has been evaluated in immunodeficient mice with xenografted tumors of human prostate cancer PC-3 cells. The daily PEITC-NAC (8 micromol/g) supplemented diet group showed a significant reduction in tumor size in 100% of the mice during the 9-week treatment period. Tumor weight at autopsy was reduced by 50% compared with mice on the diet without PEITC-NAC (P = 0.05). Mitosis and in vivo 5-bromo-2'-deoxyuridine labeled proliferating cells were reduced in these tumors. The PEITC-NAC diet up-regulated the inhibitors of cyclin-dependent kinases p21WAF-1/Cip-1 and p27Kip1, and reduced the expression of cyclins D and E, indicating they were potential molecular targets. As a result, phosphorylated Rb was significantly decreased and the G1- to S-phase transition retarded. The treated tumors also showed a significant increase in apoptosis as determined by in situ end-labeling, and by poly ADP-ribose polymerase cleavage. This study demonstrates the first in vivo evidence of dietary PEITC-NAC inhibiting tumorigenesis of prostate cancer cells. PEITC-NAC may prevent initiation of carcinogenesis and modulate the post-initiation phase by targeting cell cycle regulators and apoptosis induction.

  20. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Husain Syed A

    2011-04-01

    Full Text Available Abstract Background- Specific types of high risk Human papillomaviruses (HR-HPVs particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1 plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated. Results- We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3. Conclusion- These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer

  1. Ginsenoside Rb1, Rg1 and three extracts of traditional Chinese medicine attenuate ultraviolet B-induced G1 growth arrest in HaCaT cells and dermal fibroblasts involve down-regulating the expression of p16, p21 and p53.

    Science.gov (United States)

    Wang, Xiao-Yong; Wang, Yun-Gui; Wang, Yan-Fei

    2011-08-01

    The aims of this study were to confirm whether traditional Chinese medicine ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1), polygonum multiflorum (PM), ginkgo extract (GE) and lycium barbarum polysaccharide (LBP) can attenuate G1 growth arrest of HaCaT cells and dermal fibroblasts induced by 10 subcytotoxic ultraviolet B (UVB) exposures, and to explore the possible mechanism in terms of the expression of cell-cycle regulatory proteins p16, p21 and p53. Ten subcytotoxic exposures to UVB induced G1 growth arrest of HaCaT cells and dermal fibroblasts. Cell-cycle analysis was performed using flow cytometry, and mRNA levels of p16, p21 and p53 were detected by a reverse transcription-polymerase chain reaction (RT-PCR), and protein levels were detected using Western blot analysis. Five types of traditional Chinese medicine attenuated UVB-induced G1 growth arrest. The mRNA and protein levels of p16, p21 and p53 in HaCaT cells and dermal fibroblasts increased after UVB irradiation, but pretreatment with five types of traditional Chinese medicine decreased the expression of p16, p21 and p53. These results indicated that five types of traditional Chinese medicine can attenuate G1 growth arrest of HaCaT cells and dermal fibroblasts induced by UVB exposures, which was caused by down-regulating the expression of cell-cycle regulatory proteins p16, p21 and p53. © 2011 John Wiley & Sons A/S.

  2. Elastic behavior and platelet retraction in low- and high-density fibrin gels.

    Science.gov (United States)

    Wufsus, Adam R; Rana, Kuldeepsinh; Brown, Andrea; Dorgan, John R; Liberatore, Matthew W; Neeves, Keith B

    2015-01-06

    Fibrin is a biopolymer that gives thrombi the mechanical strength to withstand the forces imparted on them by blood flow. Importantly, fibrin is highly extensible, but strain hardens at low deformation rates. The density of fibrin in clots, especially arterial clots, is higher than that in gels made at plasma concentrations of fibrinogen (3-10 mg/mL), where most rheology studies have been conducted. Our objective in this study was to measure and characterize the elastic regimes of low (3-10 mg/mL) and high (30-100 mg/mL) density fibrin gels using shear and extensional rheology. Confocal microscopy of the gels shows that fiber density increases with fibrinogen concentration. At low strains, fibrin gels act as thermal networks independent of fibrinogen concentration. Within the low-strain regime, one can predict the mesh size of fibrin gels by the elastic modulus using semiflexible polymer theory. Significantly, this provides a link between gel mechanics and interstitial fluid flow. At moderate strains, we find that low-density fibrin gels act as nonaffine mechanical networks and transition to affine mechanical networks with increasing strains within the moderate regime, whereas high-density fibrin gels only act as affine mechanical networks. At high strains, the backbone of individual fibrin fibers stretches for all fibrin gels. Platelets can retract low-density gels by >80% of their initial volumes, but retraction is attenuated in high-density fibrin gels and with decreasing platelet density. Taken together, these results show that the nature of fibrin deformation is a strong function of fibrin fiber density, which has ramifications for the growth, embolization, and lysis of thrombi.

  3. Compensated readout for high-density MOS-gated memristor crossbar array

    KAUST Repository

    Zidan, Mohammed A.

    2015-01-01

    Leakage current is one of the main challenges facing high-density MOS-gated memristor arrays. In this study, we show that leakage current ruins the memory readout process for high-density arrays, and analyze the tradeoff between the array density and its power consumption. We propose a novel readout technique and its underlying circuitry, which is able to compensate for the transistor leakage-current effect in the high-density gated memristor array.

  4. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  5. [Association study between 834+7G/A and +1332C/T polymorphisms in the growth arrest specific 6 gene and risk of severe preeclampsia in Chinese population].

    Science.gov (United States)

    Ye, Liyan; Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Jinxin; Zhu, Yue; Wei, Xin; Liu, Yu; Bai, Huai

    2017-02-10

    To investigate the relationship between polymorphisms of the growth arrest specific 6 (GAS6) gene and severe preeclampsia in a South West Han Chinese population. Blood samples from 167 patients with severe preeclampsia and 312 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms. C and T allele frequencies for +1332C/T site were 85.63% and 14.37% in the patient group, respectively, and 78.04% and 21.96% in control group, respectively. The TT genotype and variant T allelic frequencies of the +1332C/T polymorphism were significantly lower in patients with severe preeclampsia than in the control group (both Ppreeclampsia was 0.602 (95%CI: 0.401-0.904) in carriers for the variant T allele (χ(2)=6.045, P=0.014). G and A allele frequencies for 834+7G/A site were 72.75% and 27.25% in case group, respectively, and 74.36% and 25.64% in control group, respectively. The genotype and allele frequencies of the 834+7G/A polymorphism in patients with severe preeclampsia and controls showed no significant differences (both P>0.05). In addition, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups. The variant GAS6+1332 T allele is associated with a decreased risk for severe preeclampsia in a South West Han Chinese population. On the other hand, the 834+7G/A polymorphism has no effect on the severe preeclampsia.

  6. Fronts under arrest: Nonlocal boundary dynamics in biology.

    Science.gov (United States)

    McCalla, Scott G; von Brecht, James H

    2016-12-01

    We introduce a minimal geometric partial differential equation framework to understand pattern formation from interacting, counterpropagating fronts. Our approach concentrates on the interfaces between different states in a system, and relies on both nonlocal interactions and mean-curvature flow to track their evolution. As an illustration, we use this approach to describe a phenomenon in bacterial colony formation wherein sibling colonies can arrest each other's growth. This arrested motion leads to static separations between healthy, growing colonies. As our minimal model faithfully recovers the geometry of these competing colonies, it captures and elucidates the key leading-order mechanisms responsible for such patterned growth.

  7. A palmitoyl conjugate of insect pentapeptide Yamamarin arrests cell proliferation and respiration

    OpenAIRE

    2010-01-01

    A palmitoyl conjugate of an insect pentapeptide that occurs in diapausing insects causes a reversible cell-cycle arrest and suppresses mitochondrial respiration. This peptide compound also causes growth arrest in murine leukemic cell line expressing human gene Bcr/Abl and a farnesoyl peptide induces embryonic diapause in Bombyx mori. These results demonstrate that the insect peptide compounds can lead to the understanding of a common pathway in developmental arrest in animals and may provide ...

  8. [Arrest of maturation in spermatogenesis].

    Science.gov (United States)

    Francavilla, S; Bellocci, M; Martini, M; Bruno, B; Moscardelli, S; Fabbrini, A; Properzi, G

    1982-07-30

    The ultrastructural aspects of the germinal epithelium of 10 infertile men affected by maturative arrest of spermatogenesis were studied. We noted an increased number of malformed germinal cells. Marginal nuclear vescicles were present in spermatogonia of patients affected by spermatogonial arrest. The few spermatid present in the germinal epithelium of the patients affected by a spermatidic arrest presented changes of the nuclear condensation, the acrosome, and the tail. The Sertoli cells presented an immature aspect of the nucleus and changes of the "mantle". A possible correlation between the Sertoli cells changes and the altered spermatogenesis was proposed.

  9. Anatomical traits related to stress in high density populations of Typha angustifolia L. (Typhaceae).

    Science.gov (United States)

    Corrêa, F F; Pereira, M P; Madail, R H; Santos, B R; Barbosa, S; Castro, E M; Pereira, F J

    2017-03-01

    Some macrophytes species show a high growth potential, colonizing large areas on aquatic environments. Cattail (Typha angustifolia L.) uncontrolled growth causes several problems to human activities and local biodiversity, but this also may lead to competition and further problems for this species itself. Thus, the objective of this study was to investigate anatomical modifications on T. angustifolia plants from different population densities, once it can help to understand its biology. Roots and leaves were collected from natural populations growing under high and low densities. These plant materials were fixed and submitted to usual plant microtechnique procedures. Slides were observed and photographed under light microscopy and images were analyzed in the UTHSCSA-Imagetool software. The experimental design was completely randomized with two treatments and ten replicates, data were submitted to one-way ANOVA and Scott-Knott test at p<0.05. Leaves from low density populations showed higher stomatal density and index. These modifications on stomatal characteristics were more evident on the leaf abaxial surface. Plants from low density populations showed thicker mesophyll and higher proportion of aerenchymal area. Roots from low density populations showed a higher proportion of the vascular cylinder. Whereas, plants from higher density populations showed greater thickness of the endodermis, exodermis, phloem and root cortex. Higher density populations showed a higher proportion of aerenchymal gaps in the root cortex. Therefore, cattail plants from populations growing under high density population show anatomical traits typical of plants under stress, which promotes the development of less functional anatomical modifications to aquatic environments.

  10. High-density cell systems incorporating polymer microspheres as microenvironmental regulators in engineered cartilage tissues.

    Science.gov (United States)

    Solorio, Loran D; Vieregge, Eran L; Dhami, Chirag D; Alsberg, Eben

    2013-06-01

    To address the significant clinical need for tissue-engineered therapies for the repair and regeneration of articular cartilage, many systems have recently been developed using bioactive polymer microspheres as regulators of the chondrogenic microenvironment within high-density cell cultures. In this review, we highlight various densely cellular systems utilizing polymer microspheres as three-dimensional (3D) structural elements within developing engineered cartilage tissue, carriers for cell expansion and delivery, vehicles for spatiotemporally controlled growth factor delivery, and directors of cell behavior via regulation of cell-biomaterial interactions. The diverse systems described herein represent a shift from the more traditional tissue engineering approach of combining cells and growth factors within a biomaterial scaffold, to the design of modular systems that rely on the assembly of cells and bioactive polymer microspheres as building blocks to guide the creation of articular cartilage. Cell-based assembly of 3D microsphere-incorporated structures represents a promising avenue for the future of tissue engineering.

  11. Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles

    Directory of Open Access Journals (Sweden)

    Mian M.K. Shahzad

    2011-04-01

    Full Text Available RNA interference holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of small interfering RNA (siRNA. To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1. In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and established a novel formulation of siRNA by incorporating it into reconstituted HDL (rHDL nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase in orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore, this novel technology could serve as the foundation for new cancer therapeutic approaches.

  12. An airline cardiac arrest program

    National Research Council Canada - National Science Library

    O'Rourke, M F; Donaldson, E; Geddes, J S

    1997-01-01

    ...) available for use on airline passengers with cardiac arrest. AEDs were installed on international Qantas aircraft and at major terminals, selected crew were trained in their use, and all crew members were trained in cardiopulmonary resuscitation...

  13. Growth arrest specific protein (GAS) 6

    DEFF Research Database (Denmark)

    Haase, T N; Rasmussen, Morten; Jaksch, C A M

    2013-01-01

    Aims/hypothesis Maternal low-protein (LP) diet during gestation results in a reduced beta cell mass in the offspring at birth and this may hamper the ability to adapt to high-energy food and sedentary lifestyle later in life. To investigate the biology behind the LP-offspring phenotype, this study...... that favours premature maturation of the beta cells....

  14. Enhancing the productivity of grasses under high-density planting by engineering light responses: from model systems to feedstocks.

    Science.gov (United States)

    Warnasooriya, Sankalpi N; Brutnell, Thomas P

    2014-06-01

    The successful commercialization of bioenergy grasses as lignocellulosic feedstocks requires that they be produced, processed, and transported efficiently. Intensive breeding for higher yields in food crops has resulted in varieties that perform optimally under high-density planting but often with high input costs. This is particularly true of maize, where most yield gains in the past have come through increased planting densities and an abundance of fertilizer. For lignocellulosic feedstocks, biomass rather than grain yield and digestibility of cell walls are two of the major targets for improvement. Breeding for high-density performance of lignocellulosic crops has been much less intense and thus provides an opportunity for improving the feedstock potential of these grasses. In this review, we discuss the role of vegetative shade on growth and development and suggest targets for manipulating this response to increase harvestable biomass under high-density planting. To engineer grass architecture and modify biomass properties at increasing planting densities, we argue that new model systems are needed and recommend Setaria viridis, a panicoid grass, closely related to major fuel and bioenergy grasses as a model genetic system.

  15. High Density Nano-Electrode Array for Radiation Detection

    Energy Technology Data Exchange (ETDEWEB)

    Mano Misra

    2010-05-07

    Bulk single crystals of Cd1-xZnxTe (x=0.04 to x=0.2) compound semiconductor is used for room temperature radiation detection. The production of large volume of Cd1-xZnxTe with low defect density is expensive. As a result there is a growing research interest in the production of nanostructured compound semiconductors such as Cd1-xZnxTe in an electrochemical route. In this investigation, Cd1-xZnxTe ternary compound semiconductor, referred as CZT, was electrodeposited in the form of nanowires onto a TiO2 nanotubular template from propylene carbonate as the non-aqueous electrolyte, using a pulse-reverse electrodeposition process at 130 ºC. The template acted as a support in growing ordered nanowire of CZT which acts as a one dimensional conductor. Cyclic Voltammogram (CV) studies were conducted in determining the potentials for the growth of nanowires of uniform stoichiometry. The morphologies and composition of CZT were characterized by using SEM, TEM and XRD. The STEM mapping carried out on the nanowires showed the uniform distribution of Cd, Zn and Te elements. TEM image showed that the nanowires were polycrystalline in nature. The Mott-Schottky analysis carried on the nanowires showed that the nanowires were a p-type semiconductor. The carrier density, band gap and resistivity of the Cd0.9Zn0.1Te nanowires were 4.29x1013 cm-3, 1.56 eV and 2.76x1011Ω-cm respectively. The high resistivity was attributed to the presence of deep defect states such as cadmium vacancies or Te antisites which were created by the anodic cycle of the pulse-reverse electrodeposition process. Stacks of series connected CZT nanowire arrays were tested with different bias potentials. The background current was in the order of tens of picoamperes. When exposed to radiation source Amerecium-241 (60 KeV, 4 μCi), the stacked CZT nanowires arrays showed sensing behavior. The sensitivity of the nanowire arrays increased as the number of stacks increased. The preliminary results indicate that the

  16. Low voltage electroosmotic pump for high density integration into microfabricated fluidic systems

    NARCIS (Netherlands)

    Heuck, F.C.A.; Staufer, U.

    2011-01-01

    A low voltage electroosmotic (eo) pump suitable for high density integration into microfabricated fluidic systems has been developed. The high density integration of the eo pump required a small footprint as well as a specific on-chip design to ventilate the electrolyzed gases emerging at the platin

  17. Stability of serum high-density lipoprotein-microRNAs for preanalytical conditions.

    Science.gov (United States)

    Ishikawa, Hiroaki; Yamada, Hiroya; Taromaru, Nao; Kondo, Kanako; Nagura, Ayuri; Yamazaki, Mirai; Ando, Yoshitaka; Munetsuna, Eiji; Suzuki, Koji; Ohashi, Koji; Teradaira, Ryoji

    2017-01-01

    Background Recently, several studies have shown that microRNAs are present in high-density lipoprotein, and high-density lipoprotein-microRNA may be a promising disease biomarker. We investigated the stability of high-density lipoprotein-microRNAs in different storage conditions as this is an important issue for its application to the field of clinical research. Methods microRNAs were extracted from the high-density lipoprotein fraction that was purified from the serum. miR-135 a and miR-223, which are known to be present in high-density lipoprotein, were quantified by quantitative real-time PCR. The influence of preanalytical parameters on the analysis of high-density lipoprotein-miRNAs was examined by the effect of RNase, storage conditions, and freezing and thawing. Results The concentrations of microRNA in high-density lipoprotein were not altered by RNase A treatment (0-100 U/mL). No significant change in these microRNAs was observed after storing serum at room temperature or 4℃ for 0-24 h, and there was a similar result in the cryopreservation for up to two weeks. Also, high-density lipoprotein-microRNAs were stable for, at least, up to five freeze-thaw cycles. Conclusions These results demonstrated that high-density lipoprotein-microRNAs are relatively resistant to various storage conditions. This study provides new and important information on the stability of high-density lipoprotein-microRNAs.

  18. High-density polyethylene-based composites with pressure-treated wood fibers

    Directory of Open Access Journals (Sweden)

    Lu Shang

    2012-11-01

    Full Text Available High-Density Polyethylene (HDPE-based composites with alkaline copper quaternary (ACQ- and micronized copper quaternary (MCQ-treated wood fibers were manufactured through injection molding. The mechanical properties, water absorption, and biological resistance properties of the fabricated composites with different coupling treatments were investigated. Composites with ACQ- and MCQ-treated wood had mechanical properties comparable with those made of untreated wood. The different coupling agents worked well for the treated wood materials. Similar water absorption behaviors were observed for the HDPE composites containing treated wood and those containing untreated wood. The results of the termite test showed that the composites containing untreated wood had slightly more weight loss. The decay test revealed that the composites containing treated wood had less decay fungal growth on the surfaces, compared with samples from untreated wood, indicating enhanced decay resistance for the composites from the treated material. The stable mechanical properties and improved biological performances of the composites containing treated wood demonstrated the feasibility of making wood-plastic composites with pressure-treated wood materials, and thus offered a practical way to recycle treated wood into value-added composites.

  19. Features of Localization of ARG-X Protease-processing in the Suprastructures of Interphase Chromatin under Conditions of Cell Cycle Arrest by Sodium Butyrate, upon Induction of Growth Morphogenesis of Mature Embryos of Winter and Spring Wheat

    Directory of Open Access Journals (Sweden)

    Ivanov R.S.

    2016-08-01

    Full Text Available A fundamental property of many organisms is the ability to feel, to assess direction of the signal action and respond to the environmental conditions. It is known that chromatin plays a major role in organizing the regulation of gene activity. However, our understanding of how state of the suprastructure organization of chromatin and its proteins reacts not only to changes in the environment, but also on the development of specific signals remains largely unclear. In the course of this work, we have analyzed the result of the various ways of chromatin modifications: the regulatory Arg-X protease-processing and inhibition of protein deacetylation with sodium butyrate. Sodium butyrate causes cell cycle arrest in the G0/G1 phase, and promotes of duration of the transcriptional activity of chromatin. Experiments on molecular-genetic state of the chromatin matrix were carried out at the induction of growth morphogenesis in the physiological period of active water absorption of mature seeds and wheat germs, which were purposefully transformed and formed in different environmental conditions. During focused, long-term transforming of spring wheat Artemovka into winter wheat Mironovskaya 808 and the last of them again into Mironovskaya Spring wheat while stopping of the cell cycle in the G0/G1 phase, mainly occurs the active Arg-X protease-processing at the level of non-histone proteins, and linker histones of suprastructures chromatin. We assume that the regulatory proteolytic processing and prolongation of acetylation of proteins can be interconnected in the regulation of conformational transitions of chromatin at the different levels of its organization: both suprastructures and at the more profound proteomic level of non-histone and histone blocks, and have its peculiarities during the period of transcriptional activation. We hope that the study peculiarities of locations of regulatory proteolysis in the conditions of inhibition of deacetylation in

  20. Anatomical traits related to stress in high density populations of Typha angustifolia L. (Typhaceae

    Directory of Open Access Journals (Sweden)

    F. F. Corrêa

    Full Text Available Abstract Some macrophytes species show a high growth potential, colonizing large areas on aquatic environments. Cattail (Typha angustifolia L. uncontrolled growth causes several problems to human activities and local biodiversity, but this also may lead to competition and further problems for this species itself. Thus, the objective of this study was to investigate anatomical modifications on T. angustifolia plants from different population densities, once it can help to understand its biology. Roots and leaves were collected from natural populations growing under high and low densities. These plant materials were fixed and submitted to usual plant microtechnique procedures. Slides were observed and photographed under light microscopy and images were analyzed in the UTHSCSA-Imagetool software. The experimental design was completely randomized with two treatments and ten replicates, data were submitted to one-way ANOVA and Scott-Knott test at p<0.05. Leaves from low density populations showed higher stomatal density and index. These modifications on stomatal characteristics were more evident on the leaf abaxial surface. Plants from low density populations showed thicker mesophyll and higher proportion of aerenchymal area. Roots from low density populations showed a higher proportion of the vascular cylinder. Whereas, plants from higher density populations showed greater thickness of the endodermis, exodermis, phloem and root cortex. Higher density populations showed a higher proportion of aerenchymal gaps in the root cortex. Therefore, cattail plants from populations growing under high density population show anatomical traits typical of plants under stress, which promotes the development of less functional anatomical modifications to aquatic environments.

  1. High Density Culture of Porphyridium cruentum in a 42 L Internal Airlift Loop Photobioreactor

    Institute of Scientific and Technical Information of China (English)

    王长海; 王逸云; 田志立

    2003-01-01

    The key limiting factors to high-density culture of Porphyridium cruentum are the uptake of light energy and nutrient by the microalgal cells. Under the optimal conditions of carrier culture, both cell mass and cell density were increased significantly up to 5.2 g/L (DW) and 5.2×107/ml. Furthermore,the effects of the liquid circulation velocity, light intensity and initial cell density on cell mass productivity of P. cruentum were investigated in a 42 L internal loop airlift photobioreactor. Although the light intensity was as low as 100 μmol/(m2@s), the light damage or the photoinhibition phenomenon was observed under the culture condition of low initial cell mass (0.10 g/L, DW) and high liquid circulation velocity (0.30 m/s). However, a higher cell growth rate and a high cell mass productivity were achieved with the same conditions only at high initial cell mass (about 0.80 g/L, DW). Under the optimal conditions, the cell specific growth rate, cell mass volumetric and areal output rate reached to 0.95 d-1,0.80 g/(L@d) and 42.5 g/(m2@d) respectively. Finally, a method of nutrient feeding and gradual increase of light intensity in different cultural stages was developed, which further improved the cell mass, cell mass volumetric and areal output rate to 5.9 g/L, 1.2 g/(L@d) and 61.7 g/(m2@d) respectively.

  2. Kaon condensation in neutron stars and high density behaviour of nuclear symmetry energy

    CERN Document Server

    Kubis, S

    1999-01-01

    We study the influence of a high density behaviour of the nuclear symmetry energy on a kaon condensation in neutron stars. We find that the symmetry energy typical for several realistic nuclear potentials, which decreases at high densities, inhibits kaon condensation for weaker kaon-nucleon couplings. There exists a threshold coupling above which the kaon condensate forms at densities exceeding some critical value. This is in contrast to the case of rising symmetry energy, as e.g. for relativistic mean field models, when the kaon condensate can form for any coupling at a sufficiently high density. Properties of the condensate are also different in both cases.

  3. High-density lipoprotein cholesterol on a roller coaster: where will the ride end?

    Science.gov (United States)

    Kronenberg, Florian

    2016-04-01

    Bowe et al. report an association between low high-density lipoprotein cholesterol concentrations and various incident chronic kidney disease end points in a cohort of almost 2 million US veterans followed for 9 years. These impressive data should be a starting point for further investigations including genetic epidemiologic investigations as well as post hoc analyses of interventional trials that target high-density lipoprotein cholesterol and, finally, studies that focus on the functionality of high-density lipoprotein particles.

  4. Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1

    NARCIS (Netherlands)

    Collado, M.; Medema, R.H.; Garcia-Cao, I.; Dubuisson, M.L.N.; Barradas, M.; Glassford, J.; Rivas, C.; Burgering, B.M.T.; Serrano, M.; Lam, E.W.-F.

    2000-01-01

    A senescence-like growth arrest is induced in mouse primary embryo fibroblasts by inhibitors of phosphoinositide 3-kinase (PI3K). We observed that senescence-like growth arrest is correlated with an increase in p27Kip1 but that down-regulation of other cyclin-dependent kinase (CDK) inhibitors, inclu

  5. Problems of house arrest application

    Directory of Open Access Journals (Sweden)

    Mikhail Vladimirovich Kolesnikov

    2015-06-01

    Full Text Available Objective to determine the position of house arrest in the system of preventive measures and to identify the main problems of criminal procedural regulation that prevent its broader use during the preliminary investigation and trial. Methods dialectical approach to the analysis of social phenomena allowing to view them in static and dynamic aspect evolutionarysynergetic paradigm providing the opportunity to explore the phenomenon under investigation with respect to the system subordinate and coordinating relationships within the system. Dialectical approach and the evolutionarysynergetic paradigm determined the choice of specific methods of research historical comparative law comparative formallegal statistical. Results the problems arising with application of house arrest are grouped by author depending on the structure of the provisions of Article 107 of the CriminalProcedural Code of the Russian Federation. The first group of problems includes the determination of the location of the accused suspect under house arrest and the scope of the legal restrictions imposed. The second group includes the establishment of terms of house arrest and their subsequent renewal or change of the preventive measure. The third group is the identification of persons to which the house arrest will be the best preventive measure. The results of the study allow to make proposals to change the current wording of Art. 107 of the CriminalProcedural Code of Russia. Scientific novelty a comprehensive study of current state of the normativelegal regulation of house arrest in the context of its practical application. Practical value the main provisions and conclusions of the article can be used in scientific and pedagogical activity when considering questions about the nature of preventive measures related to the restraint of personal liberty of the accused. nbsp

  6. Analysis of Crack Arrest Toughness.

    Science.gov (United States)

    1988-01-15

    vload(m) vp tn(m) Vertical Source Load (kN) on wedge HY80 Finite Element 0.0122 0.0099 3.81x10 -4 144 Steel Calculations Experiment 0.0122 --- 3.74x10-4...curve, are bona fide measures of the fracture arrest capability of tough ductile steels . The second is that the J-values represent the crack driving...fibrous mode of crack extension. (b) A new test method for studying fast fracture and arrest in tough steels . (c) Measurements of fast fracture and crack

  7. The stringent response and cell cycle arrest in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Daniel J Ferullo

    2008-12-01

    Full Text Available The bacterial stringent response, triggered by nutritional deprivation, causes an accumulation of the signaling nucleotides pppGpp and ppGpp. We characterize the replication arrest that occurs during the stringent response in Escherichia coli. Wild type cells undergo a RelA-dependent arrest after treatment with serine hydroxamate to contain an integer number of chromosomes and a replication origin-to-terminus ratio of 1. The growth rate prior to starvation determines the number of chromosomes upon arrest. Nucleoids of these cells are decondensed; in the absence of the ability to synthesize ppGpp, nucleoids become highly condensed, similar to that seen after treatment with the translational inhibitor chloramphenicol. After induction of the stringent response, while regions corresponding to the origins of replication segregate, the termini remain colocalized in wild-type cells. In contrast, cells arrested by rifampicin and cephalexin do not show colocalized termini, suggesting that the stringent response arrests chromosome segregation at a specific point. Release from starvation causes rapid nucleoid reorganization, chromosome segregation, and resumption of replication. Arrest of replication and inhibition of colony formation by ppGpp accumulation is relieved in seqA and dam mutants, although other aspects of the stringent response appear to be intact. We propose that DNA methylation and SeqA binding to non-origin loci is necessary to enforce a full stringent arrest, affecting both initiation of replication and chromosome segregation. This is the first indication that bacterial chromosome segregation, whose mechanism is not understood, is a step that may be regulated in response to environmental conditions.

  8. Assessing the functional properties of high-density lipoproteins : an emerging concept in cardiovascular research

    NARCIS (Netherlands)

    Triolo, Michela; Annema, Wijtske; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    2013-01-01

    Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL cholest

  9. High Density Lipoproteins and Arteriosclerosis: Role of Cholesterol Efflux and Reverse Cholesterol Transport

    National Research Council Canada - National Science Library

    von Eckardstein, Arnold; Nofer, Jerzy Roch; Assmann, Gerd

    2001-01-01

    Abstract—High density lipoprotein (HDL) cholesterol is an important risk factor for coronary heart disease, and HDL exerts various potentially antiatherogenic properties, including the mediation of reverse transport of cholesterol...

  10. Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

    NARCIS (Netherlands)

    Hendriks, H.F.J.; Veenstra, J.; Tol, A. van; Groener, J.E.M.; Schaafsma, G.

    1998-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels

  11. Test of high density UC targets development at Gatchina for neutron rich radioactive beam facilities

    CERN Document Server

    Lhersonneau, G; Lanchais, A; Rizzi, V; Tecchio, L.B; Bajeat, O; Essabaa, S; Lau, C; Cheikh Mhamed, M; Roussière, B; Barzakh, A.E; Fedorov, D.V; lonan, A.M; lvanov, V.S; Mezilev, K.A; Moroz, F.V; Orlov, S.YU; Panteleevc, V.N; Volkovc, YU.M; Dubois, M; Eléon, C; Gaubert, G; Jardin, P; Leroy, R; Saint Laurent, M.G; Villari, A.C.C; Stroe, L; 10.1016/j.nimb.2008.05.033

    2008-01-01

    Production of on-line mass separator neutron rich isotopes using fission induced by 1 GeV protons on high density uranium carbide has been investigate and results compared with the low density targets yields.

  12. Effects of Electron Screening on Electron Capture Rates in High Density Presupernova Core

    Institute of Scientific and Technical Information of China (English)

    蒋广飞; 彭秋和; 邹志刚

    2003-01-01

    Considering that the electron capture rate can be greatly reduced by the electron screening effect in the regime of high temperature and high density, we calculate the effect of electron screening on the electron capture rate for two important elements 56Ni and 55Co in the high density condition of a pre-supernova star. The effect of electron screening is so effective that the electron capture rate may be reduced to about 20%.

  13. Enforcement following 0.08% BAC law change: sex-specific consequences of changing arrest practices?

    Science.gov (United States)

    Schwartz, Jennifer; Davaran, Ardavan

    2013-10-01

    This research evaluated effects of stricter 0.08% BAC drunken driving law on changes in sex-specific DUI arrest rates, controlling for increased law enforcement resources and shifts in DUI-related behaviors. Another main purpose, the study assessed female/male differences in arrest increases due to broader enforcement standards and efforts. Panel data was assembled for 24 states over 1990-2007 on DUI arrests, alcohol policy, law enforcement resources, drinking and drunken driving prevalence. Two-way fixed-effects seemingly unrelated regression models predicted female versus male changes in DUI arrests following implementation of lower legal limits of intoxication, net controls. Findings suggest, first, that a broader legal definition of drunken driving intending to officially sanction less serious offenders (0.08% vs. 0.10% BAC) was associated with increased DUI arrests for both sexes. Second, growth in specialized DUI-enforcement units also was related to increased arrests. Whereas male and female arrest trends were equally affected by the direct net-widening effects of 0.08% BAC alcohol-policy, specialized DUI-enforcement efforts to dig deeper into the offender-pool had stronger arrest-producing effects on females, particularly prior to law change. Specifying how changes in law and enforcement resources affect arrest outcomes is an important pre-cursor to alcohol-policy analyses of effectiveness. A potential unintended consequence, effects of law and enforcement may differ across population segments. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

    Science.gov (United States)

    Lehti, Maarit; Donelan, Elizabeth; Abplanalp, William; Al-Massadi, Omar; Habegger, Kirk M; Weber, Jon; Ress, Chandler; Mansfeld, Johannes; Somvanshi, Sonal; Trivedi, Chitrang; Keuper, Michaela; Ograjsek, Teja; Striese, Cynthia; Cucuruz, Sebastian; Pfluger, Paul T; Krishna, Radhakrishna; Gordon, Scott M; Silva, R A Gangani D; Luquet, Serge; Castel, Julien; Martinez, Sarah; D'Alessio, David; Davidson, W Sean; Hofmann, Susanna M

    2013-11-26

    Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test compared with wild-type mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved glucose tolerance test, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of endurance capacity compared with wild-type mice. Circulating levels of fibroblast growth factor 21, a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high-fat diet-induced impairment of glucose homeostasis. In view of impaired mitochondrial function and decreased HDL levels in type 2 diabetes mellitus, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of type 2 diabetes mellitus beyond cardiovascular disease.

  15. High-density grids for efficient data collection from multiple crystals

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Elizabeth L.; Aguila, Laura; Alonso-Mori, Roberto; Barnes, Christopher O.; Bonagura, Christopher A.; Brehmer, Winnie; Brunger, Axel T.; Calero, Guillermo; Caradoc-Davies, Tom T.; Chatterjee, Ruchira; Degrado, William F.; Fraser, James S.; Ibrahim, Mohamed; Kern, Jan; Kobilka, Brian K.; Kruse, Andrew C.; Larsson, Karl M.; Lemke, Heinrik T.; Lyubimov, Artem Y.; Manglik, Aashish; McPhillips, Scott E.; Norgren, Erik; Pang, Siew S.; Soltis, S. M.; Song, Jinhu; Thomaston, Jessica; Tsai, Yingssu; Weis, William I.; Woldeyes, Rahel A.; Yachandra, Vittal; Yano, Junko; Zouni, Athina; Cohen, Aina E.

    2016-01-01

    Higher throughput methods to mount and collect data from multiple small and radiation-sensitive crystals are important to support challenging structural investigations using microfocus synchrotron beamlines. Furthermore, efficient sample-delivery methods are essential to carry out productive femtosecond crystallography experiments at X-ray free-electron laser (XFEL) sources such as the Linac Coherent Light Source (LCLS). To address these needs, a high-density sample grid useful as a scaffold for both crystal growth and diffraction data collection has been developed and utilized for efficient goniometer-based sample delivery at synchrotron and XFEL sources. A single grid contains 75 mounting ports and fits inside an SSRL cassette or uni-puck storage container. The use of grids with an SSRL cassette expands the cassette capacity up to 7200 samples. Grids may also be covered with a polymer film or sleeve for efficient room-temperature data collection from multiple samples. New automated routines have been incorporated into theBlu-Ice/DCSSexperimental control system to support grids, including semi-automated grid alignment, fully automated positioning of grid ports, rastering and automated data collection. Specialized tools have been developed to support crystallization experiments on grids, including a universal adaptor, which allows grids to be filled by commercial liquid-handling robots, as well as incubation chambers, which support vapor-diffusion and lipidic cubic phase crystallization experiments. Experiments in which crystals were loaded into grids or grown on grids using liquid-handling robots and incubation chambers are described. Crystals were screened at LCLS-XPP and SSRL BL12-2 at room temperature and cryogenic temperatures.

  16. Microstructural characterization and chemical compatibility of pulsed laser deposited yttria coatings on high density graphite

    Energy Technology Data Exchange (ETDEWEB)

    Sure, Jagadeesh [Corrosion Science and Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam — 603 102 (India); Mishra, Maneesha [Physical Metallurgy Group, Indira Gandhi Centre for Atomic Research, Kalpakkam-603 102 (India); Tarini, M. [SRM University, Kattankulathur-603 203 (India); Shankar, A. Ravi; Krishna, Nanda Gopala [Corrosion Science and Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam — 603 102 (India); Kuppusami, P. [Physical Metallurgy Group, Indira Gandhi Centre for Atomic Research, Kalpakkam-603 102 (India); Mallika, C. [Corrosion Science and Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam — 603 102 (India); Mudali, U. Kamachi, E-mail: kamachi@igcar.gov.in [Corrosion Science and Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam — 603 102 (India)

    2013-10-01

    Yttria coatings were deposited on high density (HD) graphite substrate by pulsed laser deposition method and subsequently annealing in vacuum at 1373 K was carried out to evaluate the thermal stability of the coatings. Yttria deposited on HD graphite samples were exposed to molten LiCl–KCl salt at 873 K for 3 h to evaluate the corrosion behavior of the coating for the purpose of pyrochemical reprocessing applications. The microstructure and the corrosion behavior of the yttria coating deposited on HD graphite in molten LiCl–KCl salt were evaluated by several characterization techniques. X-ray diffraction and Laser Raman patterns confirmed the presence of cubic phase of yttria in the coating. The surface morphology of yttria coating on HD graphite examined by scanning electron microscope and atomic force microscopy revealed the agglomeration of oxide particles and formation of clusters. After annealing at 1373 K, no appreciable grain growth of yttria particles could be observed. X-ray photoelectron spectroscopy analysis was carried out for elemental analysis before and after chemical compatibility test of the coated samples in molten LiCl–KCl salt to identify the corrosive elements present on the yttria coatings. The chemical compatibility and thermal stability of the yttria coating on HD graphite in molten LiCl–KCl salt medium have been established. - Highlights: • Y{sub 2}O{sub 3} coating was deposited on graphite by pulsed laser deposition method. • Chemical compatibility of Y{sub 2}O{sub 3} coating in LiCl–KCl salt at 873 K was studied. • Gibbs free energy change was positive for Y{sub 2}O{sub 3} reaction with Cl{sub 2}, U and UCl{sub 3}. • Y{sub 2}O{sub 3} coating exhibited better corrosion performance in molten LiCl–KCl salt.

  17. 超声对宫内胚胎停止发育诊断的应用观察%Application of ultrasound in the diagnosis of intrauterine embryo growth arrest

    Institute of Scientific and Technical Information of China (English)

    侯树新

    2015-01-01

    Objective: To analyze the characteristics of intrauterine embryo growth arrest, stop the application effect observa-tion of ultrasound in the diagnosis of intrauterine embryo development.Methods:From 2013 to 2014 in our hospital for treat-ment of 30 cases of diagnosed intrauterine embryos stop development of ultrasonic testing images were analyzed retrospectively. Results: 30 cases of embryonic images with different characteristics, in the ultrasonic observation, air sac type 11 cases, accounting for 24.4%, in the ultrasonic observation, no echo area inside the uterus appears irregular oval sacs, and the pregnancy pregnant sac is larger, the size of gestational sac size is 3~4cm. With favorable pregnancy pregnancy, the inner wall of uterus of pregnant women was clear, and the wall of the uterus pregnancy pregnant sac some separation. Pregnancy pregnant sac deformation type is 5 cases, accounting for 11%, patients with intrauterine pregnancies were more irregular shape, with a flat, C, and presents the bleak rough pregnancy pregnant sac state, no embryo. Light spot, wide type in 12 cases, accounting for 26.6%, in the acoustic observation, showed a light or facula echo obvious.Conclusion:Ultrasonic observation on development has a direct, accurate, rapid for intra-uterine embryo stops, miscarriage prevention and treatment of pregnant women without meaning, providing the reliable basis for the clinical treatment of.%目的:分析宫内胚胎停止发育的特点,观察超声在宫内胚胎停止发育诊断中的应用效果。方法选取2013到2014年在本院治疗的30例被诊断为宫内胚胎停止发育的患者的超声检测图片进行回顾分析。结果30例胚胎停止发育的图片各有特点,在超声观察下,空囊型的为11例,占36.6%,在超声观测下,子宫内部呈现出来的椭圆形的不规则囊状物无回声区,而且它的孕娠囊较大,妊娠囊大小为3~4cm,妊娠大小基本与怀孕周期一致,孕妇的

  18. 14 CFR 1203b.103 - Arrest authority.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Arrest authority. 1203b.103 Section 1203b.103 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SECURITY PROGRAMS; ARREST AUTHORITY AND USE OF FORCE BY NASA SECURITY FORCE PERSONNEL § 1203b.103 Arrest authority. (a) NASA...

  19. 33 CFR 154.822 - Detonation arresters, flame arresters, and flame screens.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Detonation arresters, flame arresters, and flame screens. 154.822 Section 154.822 Navigation and Navigable Waters COAST GUARD... BULK Vapor Control Systems § 154.822 Detonation arresters, flame arresters, and flame screens. (a)...

  20. Construction of a High-Density Genetic Map and Quantitative Trait Locus Mapping in the Sea Cucumber Apostichopus japonicus.

    Science.gov (United States)

    Tian, Meilin; Li, Yangping; Jing, Jing; Mu, Chuang; Du, Huixia; Dou, Jinzhuang; Mao, Junxia; Li, Xue; Jiao, Wenqian; Wang, Yangfan; Hu, Xiaoli; Wang, Shi; Wang, Ruijia; Bao, Zhenmin

    2015-10-06

    Genetic linkage maps are critical and indispensable tools in a wide range of genetic and genomic research. With the advancement of genotyping-by-sequencing (GBS) methods, the construction of a high-density and high-resolution linkage maps has become achievable in marine organisms lacking sufficient genomic resources, such as echinoderms. In this study, high-density, high-resolution genetic map was constructed for a sea cucumber species, Apostichopus japonicus, utilizing the 2b-restriction site-associated DNA (2b-RAD) method. A total of 7839 markers were anchored to the linkage map with the map coverage of 99.57%, to our knowledge, this is the highest marker density among echinoderm species. QTL mapping and association analysis consistently captured one growth-related QTL located in a 5 cM region of linkage group (LG) 5. An annotated candidate gene, retinoblastoma-binding protein 5 (RbBP5), which has been reported to be an important regulator of cell proliferation, was recognized in the QTL region. This linkage map represents a powerful tool for research involving both fine-scale QTL mapping and marker assisted selection (MAS), and will facilitate chromosome assignment and improve the whole-genome assembly of sea cucumber in the future.

  1. Evaluation of the transfer of Listeria monocytogenes from stainless steel and high-density polyethylene to Bologna and American cheese.

    Science.gov (United States)

    Rodríguez, Andrés; McLandsborough, Lynne A

    2007-03-01

    The objective of this study was to determine the factors involved in the transfer of Listeria monocytogenes from surfaces to foods. We evaluated the influence of surface type (stainless steel and high-density polyethylene), inoculation method (biofilm growth and attached cells), hydration level (visibly dry and wet), and food type (bologna and American cheese). Each experiment included all 16 combinations and was repeated 11 times. A four-strain cocktail of L. monocytogenes was used to inoculate stainless steel and high-density polyethylene either as growing biofilms or attached cells. Slides were placed on a universal testing machine and brought into contact with food at a constant pressure (45 kPa) and time (30 s). Food slices were blended, the number of transferred cells was determined by plating, and the efficiency of transfer (EOT) was calculated. The results strongly suggest that stainless steel surfaces transferred more L. monocytogenes to foods than did polyethylene (P = 0.05). Independent of the surface, biofilms tended to transfer more L. monocytogenes to foods (EOT = 0.57) than did attached cells (EOT = 0.16). Among foods, L. monocytogenes was transferred to bologna more easily than to cheese (P 0.05). We hypothesize that drying weakens cell-to-cell interactions in biofilms and cell-to-surface interactions of biofilms and thus allows increased transfer of cells to food products.

  2. Replicatively senescent cells are arrested in G1 and G2 phases

    Science.gov (United States)

    Mao, Zhiyong; Ke, Zhonghe; Gorbunova, Vera; Seluanov, Andrei

    2012-01-01

    Most human somatic cells do not divide indefinitely but enter a terminal growth arrest termed replicative senescence. Replicatively senescent cells are generally believed to arrest in G1 or G0 stage of the cell cycle. While doing cell cycle analysis on three different lines of normal human fibroblasts we observed that 36-60% of the replicatively senescent cells had 4N DNA content. Only up to 5% of senescent cells had more than one nucleus ruling out the possibility that the 4N cell population were G1-arrested bi-nucleated cells. Furthermore, it is unlikely that the 4N cells are tetraploids, because actively dividing pre-senescent cultures lacked the 8N tetraploid G2 population. Collectively these results suggest that the 4N population consists of G2 arrested cells. The notion that a large fraction of senescent cell population is arrested in G2 is important for understanding the biology of replicative senescence. PMID:22745179

  3. Polarization dependence of the quasi-Talbot effect of the high-density grating.

    Science.gov (United States)

    Teng, Shuyun; Guo, Wenzhen; Cheng, Chuanfu

    2010-03-01

    Diffractions by the one-dimensional high-density grating in the near field with TM and TE polarization illuminations are studied, and the diffraction intensity distributions are calculated with the finite-difference time-domain technique. The calculation results show that the diffractions of the high-density grating with different polarization illuminations are different. The quasi-Talbot image of the grating depends on the polarization of the incident wave, and the existence condition of the quasi-Talbot image of the grating in the near field also changes with the polarization of the incident wave. We present explanations based on the vector distribution of the energy flow density. These studies on the polarization dependence of the quasi-Talbot imaging of the high-density grating are helpful for the application of the grating to near-field photolithography.

  4. Neurologic management following cardiac arrest.

    Science.gov (United States)

    Bircher, N G

    1989-10-01

    Optimal neurologic outcome after cardiac arrest requires careful attention to the details of both intracranial and extracranial homeostasis. A high index of suspicion regarding the potential causes and complications of cardiac arrest facilitates discovery and treatment of problems before they adversely affect neurologic outcome. The future is bright for resuscitation research: Our fundamental understanding of cerebral ischemia and its consequences has dramatically improved, and this knowledge can hopefully be transferred to clinical useful modes of therapy. However, the transition from a promising, therapeutically effective intervention in animals to the demonstration that treatment is effective following cardiac arrest in humans is an important and difficult step. The patient population is heterogeneous before the insult, the duration and severity of the insult are variable, and the effectiveness of cardiopulmonary resuscitation varies among institutions. Therefore, the only means of demonstrating clinical efficacy is the performance of a large clinical trial. The Resuscitation Research Center at the University of Pittsburgh has developed and coordinated a multicenter, multinational team of investigators who have completed one definitive trial of postarrest barbiturate therapy and are currently completing a similar trial using a calcium entry blocker. Despite the formidable obstacles posed by such comprehensive efforts, they provide the mechanism for determining whether the cost of a new treatment modality is justified by the likelihood of improved mortality or morbidity.

  5. Non-equilibrium theory of arrested spinodal decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Olais-Govea, José Manuel; López-Flores, Leticia; Medina-Noyola, Magdaleno [Instituto de Física “Manuel Sandoval Vallarta,” Universidad Autónoma de San Luis Potosí, Álvaro Obregón 64, 78000 San Luis Potosí, SLP (Mexico)

    2015-11-07

    The non-equilibrium self-consistent generalized Langevin equation theory of irreversible relaxation [P. E. Ramŕez-González and M. Medina-Noyola, Phys. Rev. E 82, 061503 (2010); 82, 061504 (2010)] is applied to the description of the non-equilibrium processes involved in the spinodal decomposition of suddenly and deeply quenched simple liquids. For model liquids with hard-sphere plus attractive (Yukawa or square well) pair potential, the theory predicts that the spinodal curve, besides being the threshold of the thermodynamic stability of homogeneous states, is also the borderline between the regions of ergodic and non-ergodic homogeneous states. It also predicts that the high-density liquid-glass transition line, whose high-temperature limit corresponds to the well-known hard-sphere glass transition, at lower temperature intersects the spinodal curve and continues inside the spinodal region as a glass-glass transition line. Within the region bounded from below by this low-temperature glass-glass transition and from above by the spinodal dynamic arrest line, we can recognize two distinct domains with qualitatively different temperature dependence of various physical properties. We interpret these two domains as corresponding to full gas-liquid phase separation conditions and to the formation of physical gels by arrested spinodal decomposition. The resulting theoretical scenario is consistent with the corresponding experimental observations in a specific colloidal model system.

  6. High-Density Chemical Intercalation of Zero-Valent Copper into Bi 2 Se 3 Nanoribbons

    KAUST Repository

    Koski, Kristie J.

    2012-05-09

    A major goal of intercalation chemistry is to intercalate high densities of guest species without disrupting the host lattice. Many intercalant concentrations, however, are limited by the charge of the guest species. Here we have developed a general solution-based chemical method for intercalating extraordinarily high densities of zero-valent copper metal into layered Bi 2Se 3 nanoribbons. Up to 60 atom % copper (Cu 7.5Bi 2Se 3) can be intercalated with no disruption to the host lattice using a solution disproportionation redox reaction. © 2012 American Chemical Society.

  7. LTE Micro-cell Deployment for High-Density Railway Areas

    DEFF Research Database (Denmark)

    Sniady, Aleksander; Kassab, Mohamed; Soler, José

    2014-01-01

    Long Term Evolution (LTE) is a serious candidate for the future releases of the European Rail Traffic Management System (ERTMS). LTE offers more capacity and supports new communication-based applications and services for railways. Nevertheless, even with this technology, the classical macro......-cell radio deployments reach overload, especially in high-density areas, such as major train stations. In this paper, an LTE micro-cell deployment is investigated in high-density railway areas. Copenhagen Main Station is considered as a realistic deployment study case, with a set of relevant railway...

  8. Demonstration of resonant backward Raman amplification in high-density gas-jet plasma

    Science.gov (United States)

    Wu, Z. H.; Zhou, K. N.; Zheng, X. M.; Wei, X. F.; Zhu, Q. H.; Su, J. Q.; Xie, N.; Jiao, Z. H.; Peng, H.; Wang, X. D.; Sun, L.; Li, Q.; Huang, Z.; Zuo, Y. L.

    2016-10-01

    Backward Raman amplification was observed in a 0.7 mm-long high-density gas jet plasma. The 800 nm 30 fs seed pulse was amplified by a factor  ∼28, with an output energy of 2.8 mJ. The output spectra showed that the waveband around 800 nm was significantly amplified. The experimental result demonstrated that the resonant Raman amplification can be realized in high-density plasma against strong plasma instability.

  9. Interplay between spin polarization and color superconductivity in high density quark matter

    DEFF Research Database (Denmark)

    Tsue, Yasuhiko; da Providência, João; Providência, Constança;

    2013-01-01

    Here, it is suggested that a four-point interaction of the tensor type may lead to spin polarization in quark matter at high density. It is found that the two-flavor superconducting phase and the spin polarized phase correspond to distinct local minima of a certain generalized thermodynamical...... potential. It follows that a transition from one to the other phase occurs, passing through true minima with both a spin polarization and a color superconducting gap. It is shown that the quark spin polarized phase is realized at rather high density, while the two-flavor color superconducting phase...

  10. Programmed cell cycle arrest is required for infection of corn plants by the fungus Ustilago maydis.

    Science.gov (United States)

    Castanheira, Sónia; Mielnichuk, Natalia; Pérez-Martín, José

    2014-12-01

    Ustilago maydis is a plant pathogen that requires a specific structure called infective filament to penetrate the plant tissue. Although able to grow, this filament is cell cycle arrested on the plant surface. This cell cycle arrest is released once the filament penetrates the plant tissue. The reasons and mechanisms for this cell cycle arrest are unknown. Here, we have tried to address these questions. We reached three conclusions from our studies. First, the observed cell cycle arrest is the result of the cooperation of at least two distinct mechanisms: one involving the activation of the DNA damage response (DDR) cascade; and the other relying on the transcriptional downregulation of Hsl1, a kinase that modulates the G2/M transition. Second, a sustained cell cycle arrest during the infective filament step is necessary for the virulence in U. maydis, as a strain unable to arrest the cell cycle was severely impaired in its ability to infect corn plants. Third, production of the appressorium, a structure required for plant penetration, is incompatible with an active cell cycle. The inability to infect plants by strains defective in cell cycle arrest seems to be caused by their failure to induce the appressorium formation process. In summary, our findings uncover genetic circuits to arrest the cell cycle during the growth of this fungus on the plant surface, thus allowing the penetration into plant tissue.

  11. DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest.

    Science.gov (United States)

    Baugh, L Ryan; Sternberg, Paul W

    2006-04-18

    Development is typically studied as a continuous process under laboratory conditions, but wild animals often develop in variable and stressful environments. C. elegans larvae hatch in a developmentally arrested state (L1 arrest) and initiate post-embryonic development only in the presence of food (E. coli in lab). In contrast to the well-studied dauer arrest, L1 arrest occurs without morphological modification, although larvae in L1 arrest are more resistant to environmental stress than developing larvae . Consistent with its role in dauer formation and aging, we show that insulin/insulin-like growth factor (IGF) signaling regulates L1 arrest. daf-2 insulin/IGF receptor mutants have a constitutive-L1-arrest phenotype when fed and extended survival of L1 arrest when starved. Conversely, daf-16/FOXO mutants have a defective-arrest phenotype, failing to arrest development and dying rapidly when starved. We show that DAF-16 is required for transcription of the cyclin-dependent kinase inhibitor cki-1 in stem cells in response to starvation, accounting for the failure of daf-16/FOXO mutants to arrest cell division during L1 arrest. Other developmental events such as cell migration, cell fusion, and expression of the microRNA lin-4, a temporal regulator of post-embryonic development, are also observed in starved daf-16/FOXO mutants. These results suggest that DAF-16/FOXO promotes developmental arrest via transcriptional regulation of numerous target genes that control various aspects of development.

  12. High-density EEG coherence analysis using functional units applied to mental fatigue

    NARCIS (Netherlands)

    Caat, Michael ten; Lorist, Monicque M.; Bezdan, Eniko; Roerdink, Jos B.T.M.; Maurits, Natasha M.

    2008-01-01

    Electroencephalography (EEG) coherence provides a quantitative measure of functional brain connectivity which is calculated between pairs of signals as a function of frequency. Without hypotheses, traditional coherence analysis would be cumbersome for high-density EEG which employs a large number of

  13. Increased Antioxidant Quality Versus Lower Quantity Of High Density Lipoprotein In Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Aydin Ozgur

    2015-10-01

    Full Text Available Background: Oxidative stress may be involved in the pathogenesis of every human disease. To understand its possible role in benign prostatic hyperplasia (BPH, we measured the overall oxidative status of patients with BPH and the serum activity of the high density lipoprotein (HDL-related antioxidant enzymes paraoxonase 1 (PON1 and arylesterase (ARE.

  14. Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?

    NARCIS (Netherlands)

    J.S. Rana; S.M. Boekholdt

    2010-01-01

    Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the

  15. Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

    NARCIS (Netherlands)

    Hendriks, H.F.J.; Veenstra, J.; Tol, A. van; Groener, J.E.M.; Schaafsma, G.

    1998-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels we

  16. High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans

    NARCIS (Netherlands)

    Birjmohun, Rakesh S; van Leuven, Sander I; Levels, Johannes H M; van 't Veer, Cornelis; Kuivenhoven, Jan Albert; Meijers, Joost C M; Levi, Marcel; Kastelein, John J P; van der Poll, Tom; Stroes, Erik S G

    2007-01-01

    OBJECTIVE: Low high-density lipoprotein (HDL) cholesterol is a strong independent cardiovascular risk factor, which has been attributed to its role in reverse cholesterol transport. Whereas HDL also has potent antiinflammatory effects, the relevance of this property remains to be established in huma

  17. 77 FR 19076 - High Density Traffic Airports; Notice of Determination Regarding Low Demand Periods at Ronald...

    Science.gov (United States)

    2012-03-30

    ...\\ 33 FR 17896 (Dec. 3, 1968). In 1985, the FAA issued part 93 subpart S (the ``Buy/Sell Rule'').\\2\\ As... the 0600 hour is not a low demand period.\\3\\ \\2\\ 50 FR 52195 (Dec. 20, 1985). \\3\\ 76 FR 58393 (Sept... Federal Aviation Administration 14 CFR Part 93 High Density Traffic Airports; Notice of...

  18. Comparing high density LIDAR and medium resolution GPS generated elevation data for predicting yield stability

    Science.gov (United States)

    High density light detection and ranging (LIDAR) imaging has been shown to be able to define yield stability areas of a field for multi-cropping. Since LIDAR imaging is expensive and not widely available, we hypothesized that medium resolution GPS elevation data which is commonly collected with var...

  19. Amorphous silicon rich silicon nitride optical waveguides for high density integrated optics

    DEFF Research Database (Denmark)

    Philipp, Hugh T.; Andersen, Karin Nordström; Svendsen, Winnie Edith

    2004-01-01

    Amorphous silicon rich silicon nitride optical waveguides clad in silica are presented as a high-index contrast platform for high density integrated optics. Performance of different cross-sectional geometries have been measured and are presented with regards to bending loss and insertion loss...

  20. THE GRAFTING OF MALEIC-ANHYDRIDE ON HIGH-DENSITY POLYETHYLENE IN AN EXTRUDER

    NARCIS (Netherlands)

    GANZEVELD, KJ; JANSSEN, LPBM

    The grafting of maleic anhydride (MAH) on high density polyethylene in a counter-rotating twin screw extruder has been studied. As the reaction kinetics appear to be affected by mass transfer, good micro mixing in the extruder is important. Due to the competing mechanisms of increasing mixing and

  1. How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

    DEFF Research Database (Denmark)

    Karilainen, Topi; Vuorela, Timo; Vattulainen, Ilpo

    2015-01-01

    We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect on ...

  2. Assessing the feasibility of high-density subsurface heat extraction in urban areas

    Science.gov (United States)

    Abesser, Corinna; Busby, Jonathan

    2017-04-01

    The subsurface is increasingly utilized as a heat source (sink) for use in heating (and cooling) applications. This is driven by the need to increase the amount of heat generated from renewable sources to meet the EU renewable energy target of 12% by 2020. This study explores the feasibility, performance and long-term sustainability of high density, closed-loop GSHP installations in urban areas. Specifically, it employs a 2D, finite element, heat transport model to assess the impact of high density heat extraction in a residential area in Reading. A block of semi-detached houses is modelled, assuming that separate GSHP systems are installed in every property. The model considers conductive and advective heat transport. Uncertainties are explored through varying thermal properties and groundwater gradients across the site. Different heat demand scenarios are evaluated and the impact on the subsurface temperature distribution and on heat pump efficiency is assessed. The scenarios are selected to represent variations in inter-annual weather pattern, heating pattern and building insulation standards. Results indicate that high density heat extraction for domestic heating can be sustainable over the lifespan expected for GSHP systems (of around 20 years), in particular where heat demand is reduced by home improvement measures. Based on the results, recommendations are being presented for the sustainable deployment of high density GSHP installation in urban areas.

  3. Behavior and Preparedness to Fire Hazard in High Density Settlements in Bandung

    Directory of Open Access Journals (Sweden)

    Saut Sagala

    2016-08-01

    Full Text Available Fire is one of the hazards that may affect urban areas with high density settlements. Thus, research on fire mitigation is important to be conducted. This paper examines the behavior and preparedness of occupants in high density settlements towards fire risks in urban area. The case study is located at Kelurahan Sukahaji, Kecamatan Babakan Ciparay, Bandung that has very high density settlement as well as prone to fire hazards. This study assess 232 respondents in the study areas on information related to demography, understanding about fire, behavior and preparedness. The respondents understanding on the types of fire sources are still low. Similarly, the behavior related to the activites using fire are still dangerous because some activities are conducted with other activities which make people less aware of the fire hazards. Nevertheless, their knowledge on how to extinguish fires are quite good. This paper recommends more trainings on knowledge of fire source and behavior to be conducted to occupants living in high density settlements in order to reduce fire disaster risk.

  4. THE GRAFTING OF MALEIC-ANHYDRIDE ON HIGH-DENSITY POLYETHYLENE IN AN EXTRUDER

    NARCIS (Netherlands)

    GANZEVELD, KJ; JANSSEN, LPBM

    1992-01-01

    The grafting of maleic anhydride (MAH) on high density polyethylene in a counter-rotating twin screw extruder has been studied. As the reaction kinetics appear to be affected by mass transfer, good micro mixing in the extruder is important. Due to the competing mechanisms of increasing mixing and de

  5. Deep anisotropic dry etching of silicon microstructures by high-density plasmas

    NARCIS (Netherlands)

    Blauw, M.A.

    2004-01-01

    This thesis deals with the dry etching of deep anisotropic microstructures in monocrystalline silicon by high-density plasmas. High aspect ratio trenches are necessary in the fabrication of sensitive inertial devices such as accellerometers and gyroscopes. The etching of silicon in fluorine-based

  6. Fluidisation and dispersion behaviour of small high density pellicular expanded bed adsorbents

    DEFF Research Database (Denmark)

    Theodossiou, Irini; Elsner, H.D.; Thomas, Owen R. T.;

    2002-01-01

    The fluidisation and dispersion properties of various agarose-based expanded bed matrices-small high density stainless steel cored prototypes and standard commercial types-were studied in I-cm diameter expanded bed contactors in which fluid entering the column base is locally stirred. In all cases...

  7. The HDL hypothesis : does high-density lipoprotein protect from atherosclerosis?

    NARCIS (Netherlands)

    Vergeer, Menno; Holleboom, Adriaan G; Kastelein, John J P; Kuivenhoven, Jan Albert

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  8. Amorphous silicon rich silicon nitride optical waveguides for high density integrated optics

    DEFF Research Database (Denmark)

    Philipp, Hugh T.; Andersen, Karin Nordström; Svendsen, Winnie Edith

    2004-01-01

    Amorphous silicon rich silicon nitride optical waveguides clad in silica are presented as a high-index contrast platform for high density integrated optics. Performance of different cross-sectional geometries have been measured and are presented with regards to bending loss and insertion loss....... A sample double ring add-drop filter is presented....

  9. High-Density Lipoprotein Modulates Glucose Metabolism in Patients With Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Drew, Brian G.; Duffy, Stephen J.; Formosa, Melissa F.; Natoli, Alaina K.; Henstridge, Darren C.; Penfold, Sally A.; Thomas, Walter G.; Mukhamedova, Nigora; de Courten, Barbora; Forbes, Josephine M.; Yap, Felicia Y.; Kaye, David M.; van Hall, Gerrit; Febbraio, Mark A.; Kemp, Bruce E.; Sviridov, Dmitri; Steinberg, Gregory R.; Kingwell, Bronwyn A.

    2009-01-01

    Background-Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activat

  10. Properties of high density polyethylene – Paulownia wood flour composites via injection molding

    Science.gov (United States)

    Paulownia wood (PW) flour is evaluated as a bio-based fiber reinforcement. Composites of high density polyethylene (HDPE), 25% by weight of PW, and either 0% or 5% by weight of maleated polyethylene (MAPE) were produced by twin screw compounding followed by injection molding. Molded test composite...

  11. Carbon transport and escape fraction in a high density plasma beam

    NARCIS (Netherlands)

    van Swaaij, G. A.; Bystrov, K.; Borodin, D.; Kirschner, A.; Zaharia, T.; van der Vegt, L. B.; De Temmerman, G.; W. J. Goedheer,

    2013-01-01

    Hydrocarbon injection experiments on molybdenum targets facing high-density plasmas in Pilot-PSI were simulated with the 3D Monte Carlo impurity transport and PSI code ERO. Impurity transport and calculation of redeposition profiles were decoupled by calculating carbon redistribution matrices with E

  12. The (Anomalous) Hall Magnetometer as an Analysis Tool for High Density Recording Media

    NARCIS (Netherlands)

    Haan, de S.; Lodder, J.C.

    1991-01-01

    In this work an evaluation tool for the characterization of high-density recording thin film media is discussed. The measurement principles are based on the anomalous and the planar Hall effect. We used these Hall effects to characterize ferromagnetic Co-Cr films and Co/Pd multilayers having perpend

  13. Effect of resin variables on the creep behavior of high density hardwood composite panels

    Science.gov (United States)

    R.C. Tang; Jianhua Pu; C.Y Hse

    1993-01-01

    The flexural creep behavior of oriented strandboards (OSB) fabricated with mixed high, density hardwood flakes was investigated. Three types of adhesives, liquid phenolic-formaldehyde (LPF), melamine modified urea-formaldehyde (MUF), and LPF (face)/MUF (core) were chosen in this investigation. The resin contents (RC) used were 3.5 percent and 5.0 percent. The flakes...

  14. Residual gas entering high density hydrogen plasma: rarefaction due to rapid heating

    NARCIS (Netherlands)

    N. den Harder,; D.C. Schram,; W. J. Goedheer,; de Blank, H. J.; M. C. M. van de Sanden,; van Rooij, G. J.

    2015-01-01

    The interaction of background molecular hydrogen with magnetized (0.4 T) high density (1–5 × 10 20  m −3 ) low temperature (∼3 eV) hydrogen plasma was inferred from the Fulcher band emission in the linear plasma generator Pilot-PSI. In the plasma center,

  15. Evaluation of pyrus and quince rootstocks for high density pear orchards

    NARCIS (Netherlands)

    Maas, F.M.

    2008-01-01

    High density planting systems are a prerequisite to economise the use of land and labour costs of orchards. Dwarfing rootstocks controlling the vigour of the scion cultivars form the basis for such orchards (Wertheim and Webster, 2005). In the Netherlands, rootstock research is limited to and focuss

  16. Analysis of renal cyst of high density containing proteinaceous fluid: report of 6 cases

    Institute of Scientific and Technical Information of China (English)

    Jin Wen; Han zhong Li; He Xiao

    2008-01-01

    Objective:To investigate clinical features and imageology of renal cysts of high density, containing proteinaceous fluid and increase the diagnosis and treatment level of this special type renal cyst. Methods:Six cases were proven to be renal cysts of high density(pathologically) from 2002 to 2007 were reviewed. Among 6 cases, 1 was in the upper pole of kidney, 4 were medial and 1 was located in the anus perineum. All were 2-5 cm in size. Ultrasonography(US) excretory unognaphy, multiphase CT and renal angiography DSA imaging was performed for preoperative diagnosis. The preoperative diagnosis found renal neoplasms in 4 and renal cysts in 2. All of them were operated by partial nephrectomy. Results:All of the 6 renal high density renal masses were reseoted surgically, which were proved pathologically to be renal cysts; high density present. All of them contained proteinaceous fluid with benign cyst walls on histologic examination. No recurrence was seen in any of these cases during a long follow-up. Conclusion:CT and B-US have a higher diagnostic value, which can show the internal shape and character better. B-US or CT guided puncturing biopsy can be better applied to atypical renal cysts. Once the correct diagnosis is acquired, laparoscopic surgical treatment should be carried out.

  17. Lower Salinomycin Concentration Increases Apoptotic Detachment in High-Density Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sungpil Yoon

    2012-10-01

    Full Text Available The present study identified a novel salinomycin (Sal sensitization mechanism in cancer. We tested whether Sal reduced proliferation in a high-density population by counting attached cell numbers after Sal treatment. Sal reduced proliferation in high-density cell populations. Longer exposure to Sal further reduced proliferation. Sal concentrations of 0.1 and 5 μM had similar sensitization effects, suggesting that Sal toxicity was minimal with longer exposure to a high-density cell population. The results suggest that Sal can be applied at a relatively low concentration for a longer time to overcome drug-resistant solid tumors. The 0.5 μM Sal treatment resulted in fewer attached cells than that of the 5 μM Sal treatment with a longer exposure. The lower Sal concentration mainly increased the number of easily detachable cells on the surface. In particular, 0.5 μM Sal increased cellular detachment of newly produced daughter cells. The easily-detachable cells were undergoing apoptosis. It seems that the 0.5 μM Sal treatment also increased cellular toxicity. These novel findings may contribute to the development of Sal-based therapy for patients with drug-resistant cancer or a high-density solid tumor.

  18. The HDL hypothesis : does high-density lipoprotein protect from atherosclerosis?

    NARCIS (Netherlands)

    Vergeer, Menno; Holleboom, Adriaan G; Kastelein, John J P; Kuivenhoven, Jan Albert

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  19. High-density lipoproteins and coronary artery disease: a single-center cohort study

    NARCIS (Netherlands)

    Schaffer, A.; Verdoia, M.; Barbieri, L.; Aprami, T.M.; Suryapranata, H.; Marino, P.; Luca, G.D.

    2014-01-01

    Our goal was to estimate the role of high-density lipoprotein cholesterol (HDL-C) in predicting the prevalence and extent of coronary artery disease (CAD) in 3280 patients undergoing coronary angiography. Predictors of lower HDL levels (<32 mg/dL) were male gender (P < .001), diabetes mellitus

  20. Mechanical properties of high density polyethylene--pennycress press cake composites

    Science.gov (United States)

    Pennycress press cake (PPC) is evaluated as a bio-based fiber reinforcement. PPC is a by-product of crop seed oil extraction. Composites with a high density polyethylene (HDPE) matrix are created by twin screw compounding of 25% by weight of PPC and either 0% or 5% by weight of maleated polyethyle...

  1. High-density EEG coherence analysis using functional units applied to mental fatigue

    NARCIS (Netherlands)

    Caat, Michael ten; Lorist, Monicque M.; Bezdan, Eniko; Roerdink, Jos B.T.M.; Maurits, Natasha M.

    2008-01-01

    Electroencephalography (EEG) coherence provides a quantitative measure of functional brain connectivity which is calculated between pairs of signals as a function of frequency. Without hypotheses, traditional coherence analysis would be cumbersome for high-density EEG which employs a large number of

  2. Some considerations of organic materials for high density optical disk data storage

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The application possibilities of organic materials for high density optical disk data storage are discussed.Several points,such as physical and chemical stabilities,wavelength match and reversible property changes,which should be taken into consideration,are presented.

  3. Uniqueness of the Infinite Open Cluster for High-density Percolation on Lattice Sierpinski Carpet

    Institute of Scientific and Technical Information of China (English)

    Xian Yuan WU

    2001-01-01

    We prove the uniqueness of infinite open cluster for high-density bond percolation on latticeSierpinski Carpet; forthermorc, an alternative proof of the existence of phase transition of the modelis given. A rescaling technique is developed and used as the main tool of our proofs.

  4. Principle and application of high density spatial sampling in seismic migration

    Science.gov (United States)

    Li, Zi-Shun

    2012-06-01

    To avoid spatial aliasing problems in broad band high resolution seismic sections, I present a high density migration processing solution. I first analyze the spatial aliasing definition for stack and migration seismic sections and point out the differences between the two. We recognize that migration sections more often show spatial aliasing than stacked sections. Second, from wave propagation theory, I know that migration output is a new spatial sampling process and seismic prestack time migration can provide the high density sampling to prevent spatial aliasing on high resolution migration sections. Using a 2D seismic forward modeling analysis, I have found that seismic spatial aliasing noise can be eliminated by high density spatial sampling in prestack migration. In a 3D seismic data study for Daqing Oilfield in the Songliao Basin, I have also found that seismic sections obtained by high-density spatial sampling (10 × 10 m) in prestack migration have less spatial aliasing noise than those obtained by conventional low density spatial sampling (20 × 40 m) in prestack migration.

  5. Carbamazepine induces mitotic arrest in mammalian Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Perez Martin, J.M.; Fernandez Freire, P.; Labrador, V. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Hazen, M.J. [Departamento de Biologia, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)], E-mail: mariajose.hazen@uam.es

    2008-01-01

    We reported recently that the anticonvulsant drug carbamazepine, at supratherapeutic concentrations, exerts antiproliferative effects in mammalian Vero cells, but the underlying mechanism has not been elucidated. This motivates us to examine rigorously whether growth arrest was associated with structural changes in cellular organization during mitosis. In the present work, we found that exposure of the cells to carbamazepine led to an increase in mitotic index, mainly due to the sustained block at the metaphase/anaphase boundary, with the consequent inhibition of cell proliferation. Indirect immunofluorescence, using antibodies directed against spindle apparatus proteins, revealed that mitotic arrest was associated with formation of monopolar spindles, caused by impairment of centrosome separation. The final consequence of the spindle defects induced by carbamazepine, depended on the duration of cell cycle arrest. Following the time course of accumulation of metaphase and apoptotic cells during carbamazepine treatments, we observed a causative relationship between mitotic arrest and induction of cell death. Conversely, cells released from the block of metaphase by removal of the drug, continued to progress through mitosis and resume normal proliferation. Our results show that carbamazepine shares a common antiproliferative mechanism with spindle-targeted drugs and contribute to a better understanding of the cytostatic activity previously described in Vero cells. Additional studies are in progress to extend these initial findings that define a novel mode of action of carbamazepine in cultured mammalian cells.

  6. A palmitoyl conjugate of insect pentapeptide Yamamarin arrests cell proliferation and respiration.

    Science.gov (United States)

    Sato, Yosinori; Yang, Ping; An, Ying; Matsukawa, Kazushige; Ito, Kikukatsu; Imanishi, Shigeo; Matsuda, Hirokazu; Uchiyama, Yusuke; Imai, Kunio; Ito, Shigeki; Ishida, Yoji; Suzuki, Koichi

    2010-05-01

    A palmitoyl conjugate of an insect pentapeptide that occurs in diapausing insects causes a reversible cell-cycle arrest and suppresses mitochondrial respiration. This peptide compound also causes growth arrest in murine leukemic cell line expressing human gene Bcr/Abl and a farnesoyl peptide induces embryonic diapause in Bombyx mori. These results demonstrate that the insect peptide compounds can lead to the understanding of a common pathway in developmental arrest in animals and may provide a new peptidominetic analog in the development of biopharmaceuticals and pest management.

  7. Ent-11α-Hydroxy-15-oxo-kaur-16-en-19-oic-acid Inhibits Growth of Human Lung Cancer A549 Cells by Arresting Cell Cycle and Triggering Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Li Li; George G Chen; Ying-nian Lu; Yi Liu; Ke-feng Wu; Xian-ling Gong; Zhan-ping Gou; Ming-yue Li; Nian-ci Liang

    2012-01-01

    Objective:To examine the apoptotic effect of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F),a compound isolated from Pteris semipinnata L(PsL),in human lung cancer A549 cells.Methods:A549 cells were treated with 5F (0-80 μg/ml) for different time periods.Cytotoxicity was examined using a MTT method.Cell cycle was examined using propidium iodide staining.Apoptosis was examined using Hoechst 33258 staining,enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis.Expression of representative apoptosis-related proteins was evaluated by Western blot analysis.Reactive oxygen species (ROS) level was measured using standard protocols.Potential interaction of 5F with cisplatin was also examined.Results:5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner.5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase.Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis.The expression of p21 was increased.5F exposure also increased Bax expression,release of cytochrome c and apoptosis inducing factor (AIF),and activation of caspase-3.5F significantly sensitized the cells to cisplatin toxicity Interestingly,treatment with 5F did not increase ROS,but reduced ROS production induced by cisplatin.Conclusion:SF could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis.

  8. Cholera toxin, a typical protein kinase A activator, induces G1 phase growth arrest in human bladder transitional cell carcinoma cells via inhibiting the c-Raf/MEK/ERK signaling pathway.

    Science.gov (United States)

    Zheng, Xiaoke; Ou, Yanqiu; Shu, Minfeng; Wang, Youqiong; Zhou, Yuxi; Su, Xingwen; Zhu, Wenbo; Yin, Wei; Li, Shifeng; Qiu, Pengxin; Yan, Guangmei; Zhang, Jingxia; Hu, Jun; Xu, Dong

    2014-05-01

    The biotoxin cholera toxin has been demonstrated to have anti-tumor activity in numerous types of cancer, including glioma. However, the role of cholera toxin in the tumorigenesis of transitional cell carcinoma (TCC), the most common malignant tumor of the bladder, remains to be elucidated. To address this, in the present study, two TCC cell lines, T24 and UM-UC-3, were treated with cholera toxin [protein kinase A (PKA) activator] and KT5720 (PKA inhibitor). Cell survival and proliferation, cell cycle alterations and apoptosis were analyzed using Hoechst staining, the MTT assay, fluorescence microscopy and flow cytometry. Western blot analysis was used to detect the expression of proteins involved in cell cycle regulation. The results revealed that cholera toxin significantly induced G1 arrest and downregulated the expression of cyclin D1 and cyclin-dependent kinase 4/6 in the TCC cell lines, and this was rescued by KT5720. Furthermore, it was demonstrated that cholera toxin downregulated the activation of the c-Raf/Mek/Erk cascade, an important mediator of tumor cell proliferation, via the PKA-dependent c-Raf phosphorylation at Ser-43. Furthermore, inhibition of Mek activity with UO126 mimicked the effects of cholera toxin. In conclusion, these results confirmed that cholera toxin specifically inhibited proliferation and induced G1 phase arrest in human bladder TCC cells. This effect was due to PKA-dependent inactivation of the c-Raf/Mek/Erk pathway. This suggested that cholera toxin may be a viable therapeutic treatment against tumorigenesis and proliferation in bladder cancer.

  9. Synthetic phosphoethanolamine a precursor of membrane phospholipids reduce tumor growth in mice bearing melanoma B16-F10 and in vitro induce apoptosis and arrest in G2/M phase.

    Science.gov (United States)

    Ferreira, Adilson Kleber; Meneguelo, Renato; Marques, Fabio Luiz Navarro; Radin, Adriano; Filho, Otaviano Mendonça R; Neto, Salvador Claro; Chierice, Gilberto Orivaldo; Maria, Durvanei Augusto

    2012-10-01

    Phosphoethanolamine (Pho-s) is a compound involved in phospholipid turnover, acting as a substrate for many phospholipids of the cell membranes, especially phosphatidylcholine. We recently reported that synthetic Pho-s has potent effects on a wide variety of tumor cells. To determine if Pho-s has a potential antitumor activity, in this study we evaluated the activity of Pho-s against the B16-F10 melanoma both in vitro and in mice bearing a dorsal tumor. The treatment of B16F10 cells with Pho-s resulted in a dose-dependent inhibition of cell proliferation. At low concentrations, this activity appears to be involved in the arrest of the cell cycle at G2/M, while at high concentrations Pho-s induces apoptosis. In accordance with these results, the loss of mitochondrial potential and increased caspase-3 activity suggest that Pho-s has dual antitumor effects; i.e. it induces apoptosis at high concentrations and modulates the cell cycle at lower concentrations. In vivo, we evaluated the effect of Pho-s in mice bearing B16-F10 melanoma. The results show that Pho-s reduces the tumoral volume increasing survival rate. Furthermore, the tumor doubling time and tumor delays were substantially reduced when compared with untreated mice. Histological analyses reveal that Pho-s induces changes in cell morphology, typical characteristics of apoptosis, in addition the large areas of necrosis correlating with a reduction of tumor size. The results presented here support the hypothesis that Pho-s has antitumor effects by the induction of apoptosis as well as the inhibition of cell proliferation by arrest at G2/M. Thus, Pho-s can be regarded as a promising agent for the treatment of melanoma. Published by Elsevier SAS.

  10. Cognitive impairment after sudden cardiac arrest

    OpenAIRE

    Jaszke-Psonka, Magdalena; Piegza, Magdalena; Ścisło, Piotr; Pudlo, Robert; Piegza, Jacek; Badura-Brzoza, Karina; Leksowska, Aleksandra; Hese, Robert T.; Gorczyca, Piotr W.

    2016-01-01

    Aim To evaluate the incidence and severity of the impairment of selected cognitive functions in patients after sudden cardiac arrest (SCA) in comparison to patients after myocardial infarction without SCA and healthy subjects and to analyze the influence of sociodemographic and clinical parameters and the duration of cardiac arrest on the presence and severity of the described disorders. Material and methods The study group comprised 30 cardiac arrest survivors, the reference group comprised ...

  11. Arresting relaxation in Pickering Emulsions

    Science.gov (United States)

    Atherton, Tim; Burke, Chris

    2015-03-01

    Pickering emulsions consist of droplets of one fluid dispersed in a host fluid and stabilized by colloidal particles absorbed at the fluid-fluid interface. Everyday materials such as crude oil and food products like salad dressing are examples of these materials. Particles can stabilize non spherical droplet shapes in these emulsions through the following sequence: first, an isolated droplet is deformed, e.g. by an electric field, increasing the surface area above the equilibrium value; additional particles are then adsorbed to the interface reducing the surface tension. The droplet is then allowed to relax toward a sphere. If more particles were adsorbed than can be accommodated by the surface area of the spherical ground state, relaxation of the droplet is arrested at some non-spherical shape. Because the energetic cost of removing adsorbed colloids exceeds the interfacial driving force, these configurations can remain stable over long timescales. In this presentation, we present a computational study of the ordering present in anisotropic droplets produced through the mechanism of arrested relaxation and discuss the interplay between the geometry of the droplet, the dynamical process that produced it, and the structure of the defects observed.

  12. High-density 3D graphene-based monolith and related materials, methods, and devices

    Energy Technology Data Exchange (ETDEWEB)

    Worsley, Marcus A.; Baumann, Theodore F.; Biener, Juergen; Charnvanichborikarn, Supakit; Kucheyev, Sergei; Montalvo, Elizabeth; Shin, Swanee; Tylski, Elijah

    2017-03-21

    A composition comprising at least one high-density graphene-based monolith, said monolith comprising a three-dimensional structure of graphene sheets crosslinked by covalent carbon bonds and having a density of at least 0.1 g/cm.sup.3. Also provided is a method comprising: preparing a reaction mixture comprising a suspension and at least one catalyst, said suspension selected from a graphene oxide (GO) suspension and a carbon nanotube suspension; curing the reaction mixture to produce a wet gel; drying the wet gel to produce a dry gel, said drying step is substantially free of supercritical drying and freeze drying; and pyrolyzing the dry gel to produce a high-density graphene-based monolith. Exceptional combinations of properties are achieved including high conductive and mechanical properties.

  13. The use of high-density concretes in radiotherapy treatment room design.

    Science.gov (United States)

    Facure, A; Silva, A X

    2007-09-01

    With the modernization of radiotherapic centers, medical linear accelerators are largely replacing (60)Co teletherapy units. In many cases, the same vault housing the (60)Co teletherapy unit is reused for the linear accelerator and, when space is at a premium, high-density concrete (3.0-5.0 g/cm(3)) is employed to provide shielding against the primary, scatter and leakage radiation. This work presents a study based on Monte Carlo simulations of transmission of some clinical photon spectra (of 4-10 MV accelerators) through some types of high-density concretes, normally used in the construction of radiotherapy bunkers. From the simulations, the initial and subsequent tenth-value layers (TVL) for these materials, taking into account realistic clinical photon spectra, are presented, for primary radiation.

  14. A complete life cycle assessment of high density polyethylene plastic bottle

    Science.gov (United States)

    Treenate, P.; Limphitakphong, N.; Chavalparit, O.

    2017-07-01

    This study was aimed to determine environmental performances of a lubricant oil bottle made from high density polyethylene and to develop potential measures for reducing its impacts. A complete life cycle assessment was carried out to understand a whole effect on the environment from acquiring, processing, using, and disposing the product. Two scenarios of disposal phase; recycle and incineration: were examined to quantify a lesser degree on environmental impact. The results illustrated that major impacts of the two scenarios were at the same categories with the highest contributor of raw material acquisition and pre-processing. However, all impacts in case of recycling provided a lower point than that in case of incineration, except mineral extraction. Finally, feasible measures for reducing the environmental impact of high density polyethylene plastic bottle were proposed in accordance with 3Rs concept.

  15. Design and performance of ultra-high-density optical fiber cable with rollable optical fiber ribbons

    Science.gov (United States)

    Hogari, Kazuo; Yamada, Yusuke; Toge, Kunihiro

    2010-08-01

    This paper proposes a novel ultra-high-density optical fiber cable that employs rollable optical fiber ribbons. The cable has great advantages in terms of cable weight and diameter, and fiber splicing workability. Moreover, it will be easy to install in a small space in underground ducts and on residential and business premises. The structural design of the rollable optical fiber ribbon is evaluated theoretically and experimentally, and an optimum adhesion pitch P in the longitudinal direction is obtained. In addition, we examined the performance of ultra-high-density cables with a small diameter that employ rollable optical fiber ribbons and bending-loss insensitive optical fibers. The transmission, mechanical and mid-span access performance of these cables was confirmed to be excellent.

  16. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

    Science.gov (United States)

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

  17. High density lipoproteins as indicators of endothelial dysfunction in children with diadetes type I

    Directory of Open Access Journals (Sweden)

    Lobanova S.M.

    2011-12-01

    Full Text Available The aim of the investigation was to study the level of blood high density lipoproteins (HDL in the groups of children with different course of diadetes type I in order to find out the dependence of course and complications of diabetes on that level. Materials and methods: Blood high density lipoprotein (HDL levels were investigated in children and adolescents with diadetes type I, depending on the duration of diadetes type I, age, stage of sexual development, the stage of diabetic nephropathy and levels of plasma endothelin-1 (E-1. Results: Decrease in HDL level with increasing duration of diadetes type I in prepubertate patients, higher indices of HDL cholesterol were determined in girls, especially with impaired puberty. HDL cholesterol was higher in diabetic nephropathy at the stage of proteinuria and high level of blood endothelin-1. Conclusion: The revealed changes were considered to cause deregulation of vascular endothelium as a manifestation of the initial stages of endothelial dysfunction

  18. High-density 3D graphene-based monolith and related materials, methods, and devices

    Science.gov (United States)

    Worsley, Marcus A.; Baumann, Theodore F.; Biener, Juergen; Charnvanichborikarn, Supakit; Kucheyev, Sergei; Montalvo, Elizabeth; Shin, Swanee; Tylski, Elijah

    2017-03-21

    A composition comprising at least one high-density graphene-based monolith, said monolith comprising a three-dimensional structure of graphene sheets crosslinked by covalent carbon bonds and having a density of at least 0.1 g/cm.sup.3. Also provided is a method comprising: preparing a reaction mixture comprising a suspension and at least one catalyst, said suspension selected from a graphene oxide (GO) suspension and a carbon nanotube suspension; curing the reaction mixture to produce a wet gel; drying the wet gel to produce a dry gel, said drying step is substantially free of supercritical drying and freeze drying; and pyrolyzing the dry gel to produce a high-density graphene-based monolith. Exceptional combinations of properties are achieved including high conductive and mechanical properties.

  19. High-density localization of active molecules using Structured Sparse Model and Bayesian Information Criterion.

    Science.gov (United States)

    Quan, Tingwei; Zhu, Hongyu; Liu, Xiaomao; Liu, Yongfeng; Ding, Jiuping; Zeng, Shaoqun; Huang, Zhen-Li

    2011-08-29

    Localization-based super-resolution microscopy (or called localization microscopy) rely on repeated imaging and localization of active molecules, and the spatial resolution enhancement of localization microscopy is built upon the sacrifice of its temporal resolution. Developing algorithms for high-density localization of active molecules is a promising approach to increase the speed of localization microscopy. Here we present a new algorithm called SSM_BIC for such purpose. The SSM_BIC combines the advantages of the Structured Sparse Model (SSM) and the Bayesian Information Criterion (BIC). Through simulation and experimental studies, we evaluate systematically the performance between the SSM_BIC and the conventional Sparse algorithm in high-density localization of active molecules. We show that the SSM_BIC is superior in processing single molecule images with weak signal embedded in strong background.

  20. Study on fracture characteristic of welded high-density polyethylene pipe

    Institute of Scientific and Technical Information of China (English)

    齐芳娟; 霍立兴; 张玉凤; 荆洪阳; 杨新岐

    2002-01-01

    Crack opening displacement(COD) was applied to characterize the fracture initiation of the tough high density polyethylene. Normal single side notched three-point bend specimens and silica rubber replica techniques were used to study the characteristic COD of high-density polyethylene pipe and its butt-fusion joints including the weld fusion zone and heat affected zone at different temperature from -78℃ to 20℃ . Testing results show that the characteristic COD appears to depend on the structural features that are determined by welding process and the testing temperature. As the temperature is lowered, the characteristic COD of all zones studied decreases. Because the welding process significantly changes some structural feature of the material, characteristic COD of the weld fusion zone is the smallest one among those of the three zones. The results can be used for the engineering design and failure analysis of HDPE pipe.

  1. Forced canonical thermalization in a hadronic transport approach at high density

    Science.gov (United States)

    Oliinychenko, Dmytro; Petersen, Hannah

    2017-03-01

    Hadronic transport approaches based on an effective solution of the relativistic Boltzmann equation are widely applied for the dynamical description of heavy ion reactions at low beam energies. At high densities, the assumption of binary interactions often used in hadronic transport approaches may not be applicable anymore. Therefore, we effectively simulate the high-density regime using the local forced canonical thermalization. This framework provides the opportunity to interpolate in a dynamical way between two different limits of kinetic theory: the dilute gas approximation and the ideal fluid case. This approach will be important for studies of the dynamical evolution of heavy ion collisions at low and intermediate energies as experimentally investigated at the beam energy scan program at RHIC, and in the future at FAIR and NICA. On the other hand, this new way of modeling hot and dense strongly interacting matter might be relevant for small systems at high energies (LHC and RHIC) as well.

  2. High-Density Physical Random Number Generator Using Spin Signals in Multidomain Ferromagnetic Layer

    Directory of Open Access Journals (Sweden)

    Sungwoo Chun

    2015-01-01

    Full Text Available A high-density random number generator (RNG based on spin signals in a multidomain ferromagnetic layer in a magnetic tunnel junction (MTJ is proposed and fabricated. Unlike conventional spin-based RNGs, the proposed method does not require one to control an applied current, leading to a time delay in the system. RNG demonstrations are performed at room temperature. The randomness of the bit sequences generated by the proposed RNG is verified using the FIPS 140-2 statistical test suite provided by the NIST. The test results validate the effectiveness of the proposed RNGs. Our results suggest that we can obtain high-density, ultrafast RNGs if we can achieve high integration on the chip.

  3. ChemicalVia: a CERN-patented technology for use in high-density circuits

    CERN Multimedia

    Patrice Loïez

    2003-01-01

    High-density multilayer printed circuits such as those pictured here are found in miniaturized modern equipment from video cameras to mobile phones. Adjacent layers in these circuits are electrically connected by microvias, consisting of a small-diameter hole (usually 50 µm) with a thin metal-deposited surface covering their cylindrical walls to ensure local conductivity between the two layers. ChemicalVia is a new method, patented by CERN, to make microvias on high-density multilayer printed circuits using chemicals rather than complex laser, plasma or photoimaging technology. The process is compatible with all standard printed-circuit assembly lines, and has the advantages of low initial investment and reduced manufacturing costs. http://www.cern.ch/ttdatabase

  4. Thermal Experimental Analysis for Dielectric Characterization of High Density Polyethylene Nanocomposites

    Directory of Open Access Journals (Sweden)

    Ahmed Thabet Mohamed

    2016-01-01

    Full Text Available The importance of nanoparticles in controlling physical properties of polymeric nanocomposite materials leads us to study effects of these nanoparticles on electric and dielectric properties of polymers in industry In this research, the dielectric behaviour of High-Density Polyethylene (HDPE nanocomposites materials that filled with nanoparticles of clay or fumed silica has been investigated at various frequencies (10 Hz-1 kHz and temperatures (20-60°C. Dielectric spectroscopy has been used to characterize ionic conduction, then, the effects of nanoparticles concentration on the dielectric losses and capacitive charge of the new nanocomposites can be stated. Capacitive charge and loss tangent in high density polyethylene nanocomposites are measured by dielectric spectroscopy. Different dielectric behaviour has been observed depending on type and concentration of nanoparticles under variant thermal conditions.

  5. Curaua fiber reinforced high-density polyethylene composites: effect of impact modifier and fiber loading

    OpenAIRE

    Jaqueline Albano de Morais; Renan Gadioli; Marco-Aurelio De Paoli

    2016-01-01

    Abstract Short fibers are used in thermoplastic composites to increase their tensile and flexural resistance; however, it often decreases impact resistance. Composites with short vegetal fibers are not an exception to this behavior. The purpose of this work is to produce a vegetal fiber reinforced composite with improved tensile and impact resistance in relation to the polymer matrix. We used poly(ethylene-co-vinyl acetate), EVA, to recover the impact resistance of high density polyethylene, ...

  6. Spatiotemporal neural dynamics of moral judgment: A high-density ERP study

    OpenAIRE

    Yoder, Keith J.; Decety, Jean

    2014-01-01

    Morality is a pervasive aspect of human nature across all cultures, and neuroscience investigations are necessary for identifying what computational mechanisms underpin moral cognition. The current study used high-density ERPs to examine how moral evaluations are mediated by automatic and controlled processes as well as how quickly information and causal-intentional representations can be extracted when viewing morally laden behavior. The study also explored the extent to which individual dis...

  7. Compatibility and Decontamination of High-Density Polyethylene Exposed to Sulfur Mustard

    Science.gov (United States)

    2014-05-01

    and taken through the entire decontamination procedure. ***For coupons 11–20, the water temperature was ~65 oC when added. In all subsequent trials...the water temperature was ~ 95 oC. NA, not applicable. 11 Table 3. Decontamination Data–Pretreated Coupons Coupon Name and Number...COMPATIBILITY AND DECONTAMINATION OF HIGH-DENSITY POLYETHYLENE EXPOSED TO SULFUR MUSTARD ECBC-TR-1235

  8. Evidence for low high-density lipoprotein cholesterol levels in Australian indigenous peoples: a systematic review

    OpenAIRE

    Lyons, Jasmine G.; O’Dea, Kerin; Karen Z Walker

    2014-01-01

    Background Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia’s Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors...

  9. Association of lipase lipoprotein polymorphisms with high-density lipoprotein and triglycerides in elderly men

    OpenAIRE

    Araujo,Lara Miguel Quirino; Cendoroglo, Maysa Seabra [UNIFESP; Gigek, Carolina de Oliveira; Chen, Elizabeth Suchi; Smith, Maria de Arruda Cardoso [UNIFESP

    2010-01-01

    Lipoprotein lipase is essential for triglyceride hydrolysis. the polymorphisms S447X in exon 9 and HindIII in intron 8 have been associated with lower triglyceride levels and lower cardiovascular risk in adult men. We examined the association of these lipoprotein lipase polymorphisms with high-density lipoprotein (HDL) and triglyceride levels in elderly men. Blood samples were obtained from 87 elderly men, 48 of whom had cardiovascular disease and 39 (controls) had no history of cardiovascula...

  10. A relation between high-density-lipoprotein cholesterol and bile cholesterol saturation.

    OpenAIRE

    Thornton, J R; Heaton, K W; Macfarlane, D.G.

    1981-01-01

    The association of cholesterol gall stones with coronary artery disease is controversial. To investigate this possible relation at the biochemical level, bile cholesterol saturation and the plasma concentrations of triglycerides, total cholesterol, and high-density-lipoprotein cholesterol (HDL cholesterol) were measured in 25 healthy, middle-aged women. Bile cholesterol saturation index was negatively correlated with HDL cholesterol. It was positively correlated with plasma triglycerides and ...

  11. Second Approximation Model for Optical Head in Super High Density Storage Technology

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The paper presents second approximation model for optical head in super high-density storage technology firstly and it is an important part for three grades approximate model of ultra-small-size quantum well corn-shaped laser and simulative calculations. It supplies the important and useful results for the NFOD optical head design with ultra thin active layer and ultra small spot laser.

  12. High-density polyethylene-based composites with pressure-treated wood fibers

    OpenAIRE

    Lu Shang; Guangping Han,; Fangzheng Zhu; Jiansheng Ding; Todd Shupe; Qingwen Wang; Qinglin Wu

    2012-01-01

    High-Density Polyethylene (HDPE)-based composites with alkaline copper quaternary (ACQ)- and micronized copper quaternary (MCQ)-treated wood fibers were manufactured through injection molding. The mechanical properties, water absorption, and biological resistance properties of the fabricated composites with different coupling treatments were investigated. Composites with ACQ- and MCQ-treated wood had mechanical properties comparable with those made of untreated wood. The different coupling ag...

  13. X-ray CT high-density artefact suppression in the presence of bones

    Energy Technology Data Exchange (ETDEWEB)

    Wei Jikun [School of Health Sciences, 550 Stadium Mall Drive, West Lafayette, IN 47907-2051 (United States); Chen Laigao [BioImaging Center of Emphasis, Pfizer Global Research and Development, 2800 Plymouth RD, Ann Arbor, MI 48105 (United States); Sandison, George A [School of Health Sciences, 550 Stadium Mall Drive, West Lafayette, IN 47907-2051 (United States); Liang Yun [Department of Radiology, Indiana University Medical School, Indianapolis, IN 46202 (United States); Xu, Lisa X [School of Mechanical Engineering, 585 Purdue Mall, West Lafayette, IN 47907-2040 (United States)

    2004-12-21

    This paper presents a novel method of reducing x-ray CT high-density artefacts generated by metal objects when abundant bone structures are present in the region of interest. This method has an advantage over previously proposed methods since it heavily suppresses the metal artefacts without introducing extra bone artefacts. The method of suppression requires that bone pixels are isolated and segmented by thresholding. Then artificial CT numbers are assigned to the bone pixels so that their projection profiles are smooth and thus can be properly simulated by a polynomial interpolation. The projection profile of the metal object is then removed to fully suppress the artefacts. The resulting processed profile is fed to a reconstruction routine and the previously preserved bone pixels added back. The new method utilizes two important features of the CT image with metal artefacts: (a) metal and bone pixels are not severely affected by the high-density artefacts and (b) the high-density artefacts can be located in specific projection channels in the profile domain, although they are spread out in the image domain. This suppression method solves the problem of CT image artefacts arising from metal objects in the body. It has the potential to greatly improve diagnostic CT imaging in the presence of these objects and treatment planning that utilizes CT for patients with metal applicators (e.g., brachytherapy for cervix cancer and prostate cryotherapy)

  14. High density porous polyethylene material (Medpor) as an unwrapped orbital implant

    Institute of Scientific and Technical Information of China (English)

    CHEN Yan-hong; CUI Hong-guang

    2006-01-01

    Objective: To introduce the clinical effect among patients who received an unwrapped orbital implant with high density porous polyethylene material (Medpor) after enucleation or evisceration. Methods: Retrospective analysis of a series of 302 patients with anophthalmia who underwent placement of an unwrapped high density porous polyethylene orbital implant. We compared the patients (n=180) who accepted primary implant placement with those (n=122) who accepted secondary implant placement. Parameters evaluated included: age at time of surgery, date of surgery, sex, implant type and size, surgery type, the surgical procedure and technique performed, and complications. Results: The time of follow-up ranged from 2.0 to 58.0 months (mean 32.5 months). A total of 5 of 302 (1.66%) cases had documented postoperative complications. The following problems were noted after surgery: implant exposure, 3 patients (0.99%); implant removed due to orbital infection, 1 patient (0.34%); ptosis, 1 patient (0.34%). There were no significant complications observed in other 297 cases and all implants showed good orbital motility. The clinical effect of primary implant placement is better than that of secondary placement. Conclusion: High density porous polyethylene material can be used successfully as an unwrapped orbital implant in anopthalmic socket surgery with minimal complications. The material is well tolerated, nonantigenic and has low rate of infection and migration.

  15. Low-enriched uranium high-density target project. Compendium report

    Energy Technology Data Exchange (ETDEWEB)

    Vandegrift, George; Brown, M. Alex; Jerden, James L.; Gelis, Artem V.; Stepinski, Dominique C.; Wiedmeyer, Stanley; Youker, Amanda; Hebden, Andrew; Solbrekken, G; Allen, C; Robertson., D; El-Gizawy, Sherif; Govindarajan, Srisharan; Hoyer, Annemarie; Makarewicz, Philip; Harris, Jacob; Graybill, Brian; Gunn, Andy; Berlin, James; Bryan, Chris; Sherman, Steven; Hobbs, Randy; Griffin, F. P.; Chandler, David; Hurt, C. J.; Williams, Paul; Creasy, John; Tjader, Barak; McFall, Danielle; Longmire, Hollie

    2016-09-01

    At present, most 99Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassembly of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.

  16. Investigation of photon shielding property changes in curing high density concrete.

    Science.gov (United States)

    Marsh, Matthew B; Peters, Christopher; Rawluk, Nicholas; Schreiner, L John

    2013-10-01

    High density concrete is usually used for radiation shielding around radiotherapy treatment rooms. Because the concrete is specified differently at the design, construction, and verification stages, the relationship between the intended performance and the actual performance of the shielding material might not be entirely clear. In this study, cylindrical samples of high density shielding concrete were taken as each section of a new radiotherapy bunker was poured. The shielding performance of each sample [measured by beam attenuation and tenth-value layers (TVL)] was evaluated for 15 MV and 6 MV x-ray beams and for the 1.25 MeV monoenergetic gamma beam from a Co source. Transmission curves to 3 TVL were mapped for a representative sample. The samples were also imaged and analyzed using Co Cone Beam Computed Tomography (CoCBCT). Results indicate no significant change in the TVL of high density concrete samples as they cure. The minor fluctuations in shielding properties observed are explained by the heterogeneous structure of the samples as indicated in the CoCBCT images.

  17. Novel LLM series high density energy materials: Synthesis, characterization, and thermal stability

    Science.gov (United States)

    Pagoria, Philip; Zhang, Maoxi; Tsyshevskiy, Roman; Kuklja, Maija

    Novel high density energy materials must satisfy specific requirements, such as an increased performance, reliably high stability to external stimuli, cost-efficiency and ease of synthesis, be environmentally benign, and be safe for handling and transportation. During the last decade, the attention of researchers has drifted from widely used nitroester-, nitramine-, and nitroaromatic-based explosives to nitrogen-rich heterocyclic compounds. Good thermal stability, the low melting point, high density, and moderate sensitivity make heterocycle materials attractive candidates for use as oxidizers in rocket propellants and fuels, secondary explosives, and possibly as melt-castable ingredients of high explosive formulations. In this report, the synthesis, characterization, and results of quantum-chemical DFT study of thermal stability of LLM-191, LLM-192 and LLM-200 high density energy materials are presented. Work performed under the auspices of the DOE by the LLNL (Contract DE-AC52-07NA27344). This research is supported in part by ONR (Grant N00014-12-1-0529) and NSF. We used NSF XSEDE (Grant DMR-130077) and DOE NERSC (Contract DE-AC02-05CH11231) resources.

  18. Synthesis of high density aviation fuel with cyclopentanol derived from lignocellulose

    Science.gov (United States)

    Sheng, Xueru; Li, Ning; Li, Guangyi; Wang, Wentao; Yang, Jinfan; Cong, Yu; Wang, Aiqin; Wang, Xiaodong; Zhang, Tao

    2015-03-01

    For the first time, renewable high density aviation fuels were synthesized at high overall yield (95.6%) by the Guerbet reaction of cyclopentanol which can be derived from lignocellulose, followed by the hydrodeoxygenation (HDO). The solvent-free Guerbet reaction of cyclopentanol was carried out under the co-catalysis of solid bases and Raney metals. Among the investigated catalyst systems, the combinations of magnesium-aluminium hydrotalcite (MgAl-HT) and Raney Ni (or Raney Co) exhibited the best performances. Over them, high carbon yield (96.7%) of C10 and C15 oxygenates was achieved. The Guerbet reaction products were further hydrodeoxygenated to bi(cyclopentane) and tri(cyclopentane) over a series of Ni catalysts. These alkanes have high densities (0.86 g mL-1 and 0.91 g mL-1) and can be used as high density aviation fuels or additives to bio-jet fuel. Among the investigated HDO catalysts, the 35 wt.% Ni-SiO2-DP prepared by deposition-precipitation method exhibited the highest activity.

  19. Optimal Thermo-Structural Analysis for High Density Package Mounting on Build-up Board

    Science.gov (United States)

    Nakanishi, Tohru; Hase, Tomohiro

    The importance of the high density packaging technology and mounting technology on the printed wiring build-up board has been increased for the consumer electric products. On the other hand, the chance to use the build-up boards for mounting the high density packages has been increased. However, the understanding that the reliability of the solder connection depends on the structure of the package, the motherboard, and the material properties, is not very high. In this paper, the reliability for high density packaging, mounted on the build-up board, is assessed. The compact numerical analysis model for the reliability assessment is suggested and the most reliable packaging design with optimizing each of the parameters is reported. For introduction to the reliability assessment of the FCA attachment, ceramic and silicon are compared as the inter-poser with the parameter of the solder height. The verification of the numerical analysis results using tests on the actual hardware is also shown. And the established numerical analysis model is applied to the study of influence of the copper balance between the front side and the back side copper layers.

  20. Seismic and structural analysis of high density/consolidated spent fuel storage racks

    Energy Technology Data Exchange (ETDEWEB)

    Shah, S.J.; Biddle, J.R.; Bennett, S.M.; Schechter, C.B. [B and W Fuel Co., Lynchburg, VA (United States); Harstead, G.A. [Harstead Engineering Associates, Inc., Old Tappan, NJ (United States); Kopecky, B. [ATEA/FRAMATOME, Carquefou (France)

    1995-12-31

    In many nuclear power plants, existing storage racks are being replaced with high-density racks to accommodate the increasing inventory of spent fuel. In the hypothetical design considered here, the high-density arrangement of fuel assemblies, or consolidated fuel canisters, is accomplished through the use of borated stainless steel (BSS) plates acting as neutron absorbers. The high-density fuel racks are simply supported by the pool floor with no structural connections to adjacent racks or to the pool walls or floor. Therefore, the racks are free standing and may slide and tip. Several time history, nonlinear, seismic analyses are required to account for variations in the coefficient of friction, rack loading configuration, ad the type of the seismic event. This paper presents several of the mathematical models usually used. The models include features to allow sliding and tipping of the racks and to represent the hydrodynamic coupling which can occur between fuel assemblies and rack cells, between adjacent racks, and between the racks and the reinforced concrete walls. A detailed model representing a single rack is used to evaluate the 3-D loading effects. This model is a controlling case for the stress analysis. A 2-D multi-rack model representing a row of racks between the spent fuel pool walls is used to evaluate the change in gaps between racks. The racks are analyzed for the fuel loading conditions of consolidated, full, empty, and half-loaded with fuel assemblies.

  1. SOL plasma measurements during high density and long duration current drive on TRIAM-1M

    Energy Technology Data Exchange (ETDEWEB)

    Takemura, Takeharu; Kawasaki, Shoji; Jotaki, Eriko; Makino, Ken-ichi; Sakamoto, Mizuki; Nakamura, Kazuo; Nakamura, Yukio; Itoh, Sanae; Itoh, Satoshi [Kyushu Univ., Kasuga, Fukuoka (Japan). Research Inst. for Applied Mechanics

    1997-02-01

    In the superconducting, strong magnetic field tokamak, TRIAM-1M, for the purpose of maintaining high density plasma for long time, the current drive experiment using 8.2 GHz lower hybrid wave has been carried out. For maintaining high density plasma for long time, it is indispensable to control gas puff and recycling from wall, as these are closely related to the structure and characteristics of boundary plasma including scrape-off layer (SOL). In this study, in the high density, long time current drive using 8.2 GHz lower hybrid wave, the electron density and electron temperature of SOL plasma were measured by using double probe, and the z-direction distribution and the toroidal magnetic field dependence of the electron density and electron temperature of SOL plasma were examined and compared with OH discharge. Also the dependence of the electron density of SOL plasma on the phase difference in a adjoining waveguide tubes was examined. The experimental setup and the double probe theory are explained. The experimental results of the change with time lapse, the z-direction distribution and the magnetic field dependence of the electron density and electron temperature of SOL plasma are reported. (K.I.)

  2. Psychopathology in Women Arrested for Domestic Violence

    Science.gov (United States)

    Stuart, Gregory L.; Moore, Todd M.; Gordon, Kristina Coop; Ramsey, Susan E.; Kahler, Christopher W.

    2006-01-01

    This study examined the prevalence of psychopathology among women arrested for violence and whether the experience of intimate partner violence (IPV) was associated with Axis I psychopathology. Women who were arrested for domestic violence perpetration and court referred to violence intervention programs (N=103) completed measures of IPV…

  3. Arrested segregative phase separation in capillary tubes

    NARCIS (Netherlands)

    Tromp, R. Hans; Lindhoud, Saskia

    2006-01-01

    Phase separation in a capillary tube with one of the phases fully wetting the capillary wall is arrested when the typical size of the phase domains reaches the value of the diameter of the tube. The arrested state consists of an alternating sequence of concave-capped and convex-capped cylindrical

  4. Evaluation of an analytic linear Boltzmann transport equation solver for high-density inhomogeneities

    Energy Technology Data Exchange (ETDEWEB)

    Lloyd, S. A. M.; Ansbacher, W. [Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada); Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia V8W 3P6 (Canada) and Department of Medical Physics, British Columbia Cancer Agency-Vancouver Island Centre, Victoria, British Columbia V8R 6V5 (Canada)

    2013-01-15

    Purpose: Acuros external beam (Acuros XB) is a novel dose calculation algorithm implemented through the ECLIPSE treatment planning system. The algorithm finds a deterministic solution to the linear Boltzmann transport equation, the same equation commonly solved stochastically by Monte Carlo methods. This work is an evaluation of Acuros XB, by comparison with Monte Carlo, for dose calculation applications involving high-density materials. Existing non-Monte Carlo clinical dose calculation algorithms, such as the analytic anisotropic algorithm (AAA), do not accurately model dose perturbations due to increased electron scatter within high-density volumes. Methods: Acuros XB, AAA, and EGSnrc based Monte Carlo are used to calculate dose distributions from 18 MV and 6 MV photon beams delivered to a cubic water phantom containing a rectangular high density (4.0-8.0 g/cm{sup 3}) volume at its center. The algorithms are also used to recalculate a clinical prostate treatment plan involving a unilateral hip prosthesis, originally evaluated using AAA. These results are compared graphically and numerically using gamma-index analysis. Radio-chromic film measurements are presented to augment Monte Carlo and Acuros XB dose perturbation data. Results: Using a 2% and 1 mm gamma-analysis, between 91.3% and 96.8% of Acuros XB dose voxels containing greater than 50% the normalized dose were in agreement with Monte Carlo data for virtual phantoms involving 18 MV and 6 MV photons, stainless steel and titanium alloy implants and for on-axis and oblique field delivery. A similar gamma-analysis of AAA against Monte Carlo data showed between 80.8% and 87.3% agreement. Comparing Acuros XB and AAA evaluations of a clinical prostate patient plan involving a unilateral hip prosthesis, Acuros XB showed good overall agreement with Monte Carlo while AAA underestimated dose on the upstream medial surface of the prosthesis due to electron scatter from the high-density material. Film measurements

  5. Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

    Science.gov (United States)

    Barash, N. R.; Nosala, C.; Pham, J. K.; McInally, S. G.; Gourguechon, S.; McCarthy-Sinclair, B.

    2017-01-01

    ABSTRACT Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCE Giardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand

  6. Diabetes Mellitus Is Associated With Reduced High-Density Lipoprotein Sphingosine-1-Phosphate Content and Impaired High-Density Lipoprotein Cardiac Cell Protection.

    Science.gov (United States)

    Brinck, Jonas W; Thomas, Aurélien; Lauer, Estelle; Jornayvaz, François R; Brulhart-Meynet, Marie-Claude; Prost, Jean-Christophe; Pataky, Zoltan; Löfgren, Patrik; Hoffstedt, Johan; Eriksson, Mats; Pramfalk, Camilla; Morel, Sandrine; Kwak, Brenda R; van Eck, Miranda; James, Richard W; Frias, Miguel A

    2016-05-01

    The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise this cardioprotective effect. We used in vitro (cardiomyocytes) and ex vivo (whole heart) models subjected to oxidative stress together with HDL isolated from diabetic patients and nondiabetic HDL glycated in vitro (methylglyoxal). Diabetic and in vitro glycated HDL were less effective (Pdiabetic patients (Pdiabetic HDL were inversely correlated with hemoglobin A1c (Pdiabetic HDL were significantly, positively correlated (both diabetic HDL increased its S1P content and restored its cardioprotective function. Our data demonstrate that glycation can reduce the S1P content of HDL, leading to increased cardiomyocyte cell death because of less effective activation of intracellular survival pathways. It has important implications for the functionality of HDL in diabetes mellitus because HDL-S1P has several beneficial effects on the vasculature. © 2016 American Heart Association, Inc.

  7. Interfacial Crack Arrest in Sandwich Panels with Embedded Crack Stoppers Subjected to Fatigue Loading

    Science.gov (United States)

    Martakos, G.; Andreasen, J. H.; Berggreen, C.; Thomsen, O. T.

    2017-02-01

    A novel crack arresting device has been implemented in sandwich panels and tested using a special rig to apply out-of-plane loading on the sandwich panel face-sheets. Fatigue crack propagation was induced in the face-core interface of the sandwich panels which met the crack arrester. The effect of the embedded crack arresters was evaluated in terms of the achieved enhancement of the damage tolerance of the tested sandwich panels. A finite element (FE) model of the experimental setup was used for predicting propagation rates and direction of the crack growth. The FE simulation was based on the adoption of linear fracture mechanics and a fatigue propagation law (i.e. Paris law) to predict the residual fatigue life-time and behaviour of the test specimens. Finally, a comparison between the experimental results and the numerical simulations was made to validate the numerical predictions as well as the overall performance of the crack arresters.

  8. Interfacial Crack Arrest in Sandwich Panels with Embedded Crack Stoppers Subjected to Fatigue Loading

    Science.gov (United States)

    Martakos, G.; Andreasen, J. H.; Berggreen, C.; Thomsen, O. T.

    2016-08-01

    A novel crack arresting device has been implemented in sandwich panels and tested using a special rig to apply out-of-plane loading on the sandwich panel face-sheets. Fatigue crack propagation was induced in the face-core interface of the sandwich panels which met the crack arrester. The effect of the embedded crack arresters was evaluated in terms of the achieved enhancement of the damage tolerance of the tested sandwich panels. A finite element (FE) model of the experimental setup was used for predicting propagation rates and direction of the crack growth. The FE simulation was based on the adoption of linear fracture mechanics and a fatigue propagation law (i.e. Paris law) to predict the residual fatigue life-time and behaviour of the test specimens. Finally, a comparison between the experimental results and the numerical simulations was made to validate the numerical predictions as well as the overall performance of the crack arresters.

  9. Cell Cycle Arrest in Archaea by the Hypusination Inhibitor N1-Guanyl-1,7-Diaminoheptane

    Science.gov (United States)

    Jansson, B. P. Mattias; Malandrin, Laurence; Johansson, Hans E.

    2000-01-01

    Hypusination is an essential posttranslational modification unique to archaeal and eukaryotic protein synthesis initiation factor 5A (aIF5A and eIF5A, respectively). We have investigated the effect of the efficient hypusination inhibitor N1-guanyl-1,7-diaminoheptane (GC7) on four archaeal and one bacterial species. We found that (i) archaea are sensitive to GC7, whereas the bacterium Escherichia coli is not, (ii) GC7 causes rapid and reversible arrest of growth of the archaeon Sulfolobus acidocaldarius, and (iii) the growth arrest is accompanied by a specific reversible arrest of the cell cycle prior to cell division. Our findings establish a link between hypusination and sustained growth of archaea and thereby provide the framework to study molecular details of archaeal cell cycle in connection with in vivo functions of hypusine and of aIF5A and eIF5A. PMID:10648545

  10. Aqueous Extracts of the Edible Gracilaria tenuistipitata are Protective Against H2O2-Induced DNA Damage, Growth Inhibition, and Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Chi-Chen Yeh

    2012-06-01

    Full Text Available Potential antioxidant properties of an aqueous extract of the edible red seaweed Gracilaria tenuistipitata (AEGT against oxidative DNA damage were evaluated. The AEGT revealed several antioxidant molecules, including phenolics, flavonoids and ascorbic acid. In a cell-free assay, the extract exhibited 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging activity that significantly reduced H2O2-induced plasmid DNA breaks in a dose-response manner (P < 0.001. The AEGT also suppressed H2O2-induced oxidative DNA damage in H1299 cells by reducing the percentage of damaged DNA in a dose-response manner (P < 0.001 as measured by a modified alkaline comet-nuclear extract (comet-NE assay. The MTT assay results showed that AEGT confers significant protection against H2O2-induced cytotoxicity and that AEGT itself is not cytotoxic (P < 0.001. Moreover, H2O2-induced cell cycle G2/M arrest was significantly released when cells were co-treated with different concentrations of AEGT (P < 0.001. Taken together, these findings suggest that edible red algae Gracilaria water extract can prevent H2O2-induced oxidative DNA damage and its related cellular responses.

  11. Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP.

    Science.gov (United States)

    Mantena, Sudheer K; Sharma, Som D; Katiyar, Santosh K

    2006-10-01

    Chemotherapeutic approach using non-toxic botanicals may be one of the strategies for the management of the skin cancers. Here we report that in vitro treatment of human epidermoid carcinoma A431 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability (3-77%, P berberine-induced G(1) cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), a simultaneous decrease in Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and enhanced binding of Cdki-Cdk. In additional studies, treatment of A431 cells with berberine (15-75 microM) for 72 h resulted in a significant dose-dependent increase in apoptosis (31-60%, P berberine-treated control (11.7%), which was associated with an increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose) polymerase. Pretreatment of A431 cells with the pan-caspase inhibitor (z-VAD-fmk) significantly blocked the berberine-induced apoptosis in A431 cells confirmed that berberine-induced apoptosis is mediated through activation of caspase 3-dependent pathway. Together, this study for the first time identified berberine as a chemotherapeutic agent against human epidermoid carcinoma A431 cells in vitro, further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of non-melanoma skin cancers.

  12. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne;

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  13. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  14. Pruning for crop regulation in high density guava (Psidium guajava L.) plantation

    Energy Technology Data Exchange (ETDEWEB)

    Thakre, M.; Lal, S.; Uniyal, S.; Goswami, A.K. Prakash. P.

    2016-11-01

    High density management and crop regulation are two important aspects in guava (Psidium guajava L.) production. Therefore, to find out the economic way of managing high density planting and crop regulation, the present work was carried out on 6-year-old guava trees of cv. Pant Prabhat under double-hedge row system of planting during 2009-10 and 2010-11. Seven different forms of pruning [FBT: flower bud thinning by hand, FBTT: flower bud thinning by hand followed by removal of terminal one leaf pair, RLFO: removal of leaves and flower buds by hand, retaining one leaf pair at the top, RLF: removal of all leaves and flowers by hand, OLPS: one leaf pair shoot pruning, FSP: full shoot pruning, OLPF: one leaf pair pruning of fruited shoots only] were studied along with control (C).Minimum annual increase in tree volume (6.764 m3) was recorded with the treatment OLPF, which was 2.31 times less than the control (15.682 m3). Highest yield during winter season (55.30 kg/tree) and total yield (59.87 kg/tree) was obtained from treatment OLPF. One leaf pair pruning of fruited shoots only (OLPF) was also found profitable among other treatments by recording cost:benefit ratio of 1:2.96. This treatment also recorded the highest return distributed in rainy as well as in winter season. On the basis of findings it can be concluded that one leaf pair pruning of fruited shoots only is suitable for profitable high density management as well as crop regulation of guava in farmer friendly manner. (Author)

  15. BioMEA: a versatile high-density 3D microelectrode array system using integrated electronics.

    Science.gov (United States)

    Charvet, Guillaume; Rousseau, Lionel; Billoint, Olivier; Gharbi, Sadok; Rostaing, Jean-Pierre; Joucla, Sébastien; Trevisiol, Michel; Bourgerette, Alain; Chauvet, Philippe; Moulin, Céline; Goy, François; Mercier, Bruno; Colin, Mikael; Spirkovitch, Serge; Fanet, Hervé; Meyrand, Pierre; Guillemaud, Régis; Yvert, Blaise

    2010-04-15

    Microelectrode arrays (MEAs) offer a powerful tool to both record activity and deliver electrical microstimulations to neural networks either in vitro or in vivo. Microelectronics microfabrication technologies now allow building high-density MEAs containing several hundreds of microelectrodes. However, dense arrays of 3D micro-needle electrodes, providing closer contact with the neural tissue than planar electrodes, are not achievable using conventional isotropic etching processes. Moreover, increasing the number of electrodes using conventional electronics is difficult to achieve into compact devices addressing all channels independently for simultaneous recording and stimulation. Here, we present a full modular and versatile 256-channel MEA system based on integrated electronics. First, transparent high-density arrays of 3D-shaped microelectrodes were realized by deep reactive ion etching techniques of a silicon substrate reported on glass. This approach allowed achieving high electrode aspect ratios, and different shapes of tip electrodes. Next, we developed a dedicated analog 64-channel Application Specific Integrated Circuit (ASIC) including one amplification stage and one current generator per channel, and analog output multiplexing. A full modular system, called BIOMEA, has been designed, allowing connecting different types of MEAs (64, 128, or 256 electrodes) to different numbers of ASICs for simultaneous recording and/or stimulation on all channels. Finally, this system has been validated experimentally by recording and electrically eliciting low-amplitude spontaneous rhythmic activity (both LFPs and spikes) in the developing mouse CNS. The availability of high-density MEA systems with integrated electronics will offer new possibilities for both in vitro and in vivo studies of large neural networks.

  16. Genome-wide copy number profiling using high-density SNP array in chickens.

    Science.gov (United States)

    Yi, G; Qu, L; Chen, S; Xu, G; Yang, N

    2015-04-01

    Phenotypic diversity is a direct consequence resulting mainly from the impact of underlying genetic variation, and recent studies have shown that copy number variation (CNV) is emerging as an important contributor to both phenotypic variability and disease susceptibility. Herein, we performed a genome-wide CNV scan in 96 chickens from 12 diversified breeds, benefiting from the high-density Affymetrix 600 K SNP arrays. We identified a total of 231 autosomal CNV regions (CNVRs) encompassing 5.41 Mb of the chicken genome and corresponding to 0.59% of the autosomal sequence. The length of these CNVRs ranged from 2.6 to 586.2 kb with an average of 23.4 kb, including 130 gain, 93 loss and eight both gain and loss events. These CNVRs, especially deletions, had lower GC content and were located particularly in gene deserts. In particular, 102 CNVRs harbored 128 chicken genes, most of which were enriched in immune responses. We obtained 221 autosomal CNVRs after converting probe coordinates to Galgal3, and comparative analysis with previous studies illustrated that 153 of these CNVRs were regarded as novel events. Furthermore, qPCR assays were designed for 11 novel CNVRs, and eight (72.73%) were validated successfully. In this study, we demonstrated that the high-density 600 K SNP array can capture CNVs with higher efficiency and accuracy and highlighted the necessity of integrating multiple technologies and algorithms. Our findings provide a pioneering exploration of chicken CNVs based on a high-density SNP array, which contributes to a more comprehensive understanding of genetic variation in the chicken genome and is beneficial to unearthing potential CNVs underlying important traits of chickens. © 2015 Stichting International Foundation for Animal Genetics.

  17. The Application of High Density Electronic Packaging for Spacecraft Cost and Mass Reduction

    Science.gov (United States)

    Lowry, Lynn E.; Prokop, Jon S.; Sandborn, Peter; Evans, Kristan

    1995-01-01

    It has become clear over the past few years that packaging of spacecraft electronic systems must be improved. Not only have the weight and volume taken up by conventional packaging and interconnect systems become excessive, but active devices have advanced to the point where system performance is often limited by the packaging. Since electronic systems account for up to 30% of the size and weight budgets of a spacecraft, the utilization of high density electronic packaging will be a very important path to overall spacecraft miniaturization. In the late 1970's high density interconnection technologies were being introduced into mainframe computer applications. Subsequently, these technologies have been applied to avionics, telecommunication, biomedical and automotive systems. In each application the driving forces behind the adoption of these technologies were; improved electrical performance, miniaturization, reduced power consumption, increased reliability and reduced manufacturing costs. The application of these technologies to planetary missions could provide significant benefits by way of reduced cost and design time if commercial technology and best commercial manufacturing practices are accepted. A mixed signal telecommunication function has been used as an example to illustrate the potential mass, volume and power reduction achievable with the implementation of high density packaging technologies. The tradeoff analysis which was performed demonstrated that packaging technology selection is application specific, and system level impact must be considered early on in the design process. The results of this study which compare size, performance, cost, risk and system level impact are given. Finally, the technical and cultural obstacles which have inhibited the implementation of these technologies is discussed. Specifically, the issues of space qualified hardware and technology availability is addressed. Space qualification is perceived by industry as being the

  18. Examination of Poststroke Alteration in Motor Unit Firing Behavior Using High-Density Surface EMG Decomposition.

    Science.gov (United States)

    Li, Xiaoyan; Holobar, Ales; Gazzoni, Marco; Merletti, Roberto; Rymer, William Zev; Zhou, Ping

    2015-05-01

    Recent advances in high-density surface electromyogram (EMG) decomposition have made it a feasible task to discriminate single motor unit activity from surface EMG interference patterns, thus providing a noninvasive approach for examination of motor unit control properties. In the current study, we applied high-density surface EMG recording and decomposition techniques to assess motor unit firing behavior alterations poststroke. Surface EMG signals were collected using a 64-channel 2-D electrode array from the paretic and contralateral first dorsal interosseous (FDI) muscles of nine hemiparetic stroke subjects at different isometric discrete contraction levels between 2 to 10 N with a 2 N increment step. Motor unit firing rates were extracted through decomposition of the high-density surface EMG signals and compared between paretic and contralateral muscles. Across the nine tested subjects, paretic FDI muscles showed decreased motor unit firing rates compared with contralateral muscles at different contraction levels. Regression analysis indicated a linear relation between the mean motor unit firing rate and the muscle contraction level for both paretic and contralateral muscles (p < 0.001), with the former demonstrating a lower increment rate (0.32 pulses per second (pps)/N) compared with the latter (0.67 pps/N). The coefficient of variation (averaged over the contraction levels) of the motor unit firing rates for the paretic muscles (0.21 ± 0.012) was significantly higher than for the contralateral muscles (0.17 ± 0.014) (p < 0.05). This study provides direct evidence of motor unit firing behavior alterations poststroke using surface EMG, which can be an important factor contributing to hemiparetic muscle weakness.

  19. Dst prediction for a period of high-density plasmas in magnetic clouds

    Science.gov (United States)

    Adachi, H.; Sakurai, T.

    We examine geomagnetic effects for high-density plasmas in magnetic clouds and their relationship to solar sources. It is well known that Bz component of interplanetary magnetic field plays an important role for estimation of Dst from solar wind parameters (Burton et al.1975). However, magnetic clouds frequently carry high-density plasmas, which are interpreted as the remnants of filament. In order to clarify their geomagnetic effects, we try to estimate Dst by adopting different methods introducing effects of solar wind parameters. In our estimation the most important point is laid on the sense of Dst variation rather than its magnitude. The most suitable estimation is obtained by setting up a threshold for plasma density, in which for a case of plasma density greater than 20 /cc the Fenrich and Luhmann (1998)'s formula should be used, while in the other cases the Burton's formula are adopted. In both estimations the O'Brien and McPherron (2000)'s ring current decay time is employed. Furthermore, we examine the solar origin corresponding to the magnetic clouds and then compared characteristic signatures of the magnetic cloud with those observed on the solar surface. As a result, we confirm that the magnetic structure of interplanetary flux rope is in good agreement with the structures of the magnetic neutral line near disappearing filaments and heliospheric current sheet (HCS). On the basis of these studies, we suggest that for the geomagnetic disturbance forecast, the effect of high-density plasmas carried with magnetic clouds should be taken into account of as well as that of interplanetary magnetic field.

  20. Quark matter at high density based on an extended confined isospin-density-dependent mass model

    Science.gov (United States)

    Qauli, A. I.; Sulaksono, A.

    2016-01-01

    We investigate the effect of the inclusion of relativistic Coulomb terms in a confined-isospin-density-dependent-mass (CIDDM) model of strange quark matter (SQM). We found that if we include the Coulomb term in scalar density form, the SQM equation of state (EOS) at high densities is stiffer but if we include the Coulomb term in vector density form it is softer than that of the standard CIDDM model. We also investigate systematically the role of each term of the extended CIDDM model. Compared with what was reported by Chu and Chen [Astrophys. J. 780, 135 (2014)], we found the stiffness of SQM EOS is controlled by the interplay among the oscillator harmonic, isospin asymmetry and Coulomb contributions depending on the parameter's range of these terms. We have found that the absolute stable condition of SQM and the mass of 2 M⊙ pulsars can constrain the parameter of oscillator harmonic κ1≈0.53 in the case the Coulomb term is excluded. If the Coulomb term is included, for the models with their parameters are consistent with SQM absolute stability condition, the 2.0 M⊙ constraint more prefers the maximum mass prediction of the model with the scalar Coulomb term than that of the model with the vector Coulomb term. On the contrary, the high densities EOS predicted by the model with the vector Coulomb is more compatible with the recent perturbative quantum chromodynamics result [1] than that predicted by the model with the scalar Coulomb. Furthermore, we also observed the quark composition in a very high density region depends quite sensitively on the kind of Coulomb term used.