14 CFR 25.809 - Emergency exit arrangement.

Science.gov (United States)

2010-01-01

... moveable door or hatch in the external walls of the fuselage, allowing an unobstructed opening to the... event of failure of the primary system. Manual operation of the exit (after failure of the primary... during flight. (i) Each emergency exit must have a means to retain the exit in the open position, once...

DNA replication initiator Cdc6 also regulates ribosomal DNA transcription initiation.

Science.gov (United States)

Huang, Shijiao; Xu, Xiaowei; Wang, Guopeng; Lu, Guoliang; Xie, Wenbing; Tao, Wei; Zhang, Hongyin; Jiang, Qing; Zhang, Chuanmao

2016-04-01

RNA-polymerase-I-dependent ribosomal DNA (rDNA) transcription is fundamental to rRNA processing, ribosome assembly and protein synthesis. However, how this process is initiated during the cell cycle is not fully understood. By performing a proteomic analysis of transcription factors that bind RNA polymerase I during rDNA transcription initiation, we identified that the DNA replication initiator Cdc6 interacts with RNA polymerase I and its co-factors, and promotes rDNA transcription in G1 phase in an ATPase-activity-dependent manner. We further showed that Cdc6 is targeted to the nucleolus during late mitosis and G1 phase in a manner that is dependent on B23 (also known as nucleophosmin, NPM1), and preferentially binds to the rDNA promoter through its ATP-binding domain. Overexpression of Cdc6 increases rDNA transcription, whereas knockdown of Cdc6 results in a decreased association of both RNA polymerase I and the RNA polymerase I transcription factor RRN3 with rDNA, and a reduction of rDNA transcription. Furthermore, depletion of Cdc6 impairs the interaction between RRN3 and RNA polymerase I. Taken together, our data demonstrate that Cdc6 also serves as a regulator of rDNA transcription initiation, and indicate a mechanism by which initiation of rDNA transcription and DNA replication can be coordinated in cells. © 2016. Published by The Company of Biologists Ltd.

Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

DEFF Research Database (Denmark)

Burbage, Marianne; Keppler, Selina J; Gasparrini, Francesca

2015-01-01

The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-de...

Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

International Nuclear Information System (INIS)

Wan, Qiaoqiao; Cho, Eunhye; Yokota, Hiroki; Na, Sungsoo

2013-01-01

Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm 2 ) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate

Rac1 and Cdc42 GTPases regulate shear stress-driven β-catenin signaling in osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Wan, Qiaoqiao; Cho, Eunhye [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Yokota, Hiroki [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Na, Sungsoo, E-mail: sungna@iupui.edu [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States)

2013-04-19

Highlights: •Shear stress increased TCF/LEF activity and stimulated β-catenin nuclear localization. •Rac1, Cdc42, and RhoA displayed distinct dynamic activity patterns under flow. •Rac1 and Cdc42, but not RhoA, regulate shear stress-driven TCF/LEF activation. •Cytoskeleton did not significantly affect shear stress-induced TCF/LEF activation. -- Abstract: Beta-catenin-dependent TCF/LEF (T-cell factor/lymphocyte enhancing factor) is known to be mechanosensitive and an important regulator for promoting bone formation. However, the functional connection between TCF/LEF activity and Rho family GTPases is not well understood in osteoblasts. Herein we investigated the molecular mechanisms underlying oscillatory shear stress-induced TCF/LEF activity in MC3T3-E1 osteoblast cells using live cell imaging. We employed fluorescence resonance energy transfer (FRET)-based and green fluorescent protein (GFP)-based biosensors, which allowed us to monitor signal transduction in living cells in real time. Oscillatory (1 Hz) shear stress (10 dynes/cm{sup 2}) increased TCF/LEF activity and stimulated translocation of β-catenin to the nucleus with the distinct activity patterns of Rac1 and Cdc42. The shear stress-induced TCF/LEF activity was blocked by the inhibition of Rac1 and Cdc42 with their dominant negative mutants or selective drugs, but not by a dominant negative mutant of RhoA. In contrast, constitutively active Rac1 and Cdc42 mutants caused a significant enhancement of TCF/LEF activity. Moreover, activation of Rac1 and Cdc42 increased the basal level of TCF/LEF activity, while their inhibition decreased the basal level. Interestingly, disruption of cytoskeletal structures or inhibition of myosin activity did not significantly affect shear stress-induced TCF/LEF activity. Although Rac1 is reported to be involved in β-catenin in cancer cells, the involvement of Cdc42 in β-catenin signaling in osteoblasts has not been identified. Our findings in this study demonstrate

Inhibition of the mitotic exit network in response to damaged telomeres.

Directory of Open Access Journals (Sweden)

Mauricio Valerio-Santiago

Full Text Available When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN, in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression.

Regulation of the vertebrate cell cycle by the cdc2 protein kinase

International Nuclear Information System (INIS)

Draetta, G.; Brizuela, L.; Moran, B.; Beach, D.

1988-01-01

A homolog of the cdc2/CDC28 protein kinase of yeast is found in all vertebrate species that have been investigated. Human cdc2 exists as a complex with a 13-kD protein that is homologous to the suc1 gene product of fission yeast. In both human and fission yeast cells, the protein kinase also exists in a complex with a 62-kD polypeptide that has not been identified genetically but acts as a substrate in vitro. The authors have studied the properties of the protein kinase in rat and human cells, as well as in Xenopus eggs. They find that in baby rat kidney (BRK) cells, which are quiescent in cell culture, the cdc2 protein is not synthesized. However, synthesis is rapidly induced in response to proliferative activation by infection with adenovirus. In human HeLa cells, the protein kinase is present continuously. It behaves as a cell-cycle oscillator that is inactive in G 1 but displays maximal enzymatic activity during mitotic metaphase. These observations indicate that in a wide variety of vertebrate cells, the cdc2 protein kinase is involved in regulating mitosis. The authors' approach taken toward study of the cdc2 protein kinase highlights the possibilities that now exist for combining the advantages of ascomycete genetics with the cell-free systems of Xenopus and the biochemical advantages of tissue culture cells to investigate fundamental problems of the cell cycle

Exit from contract

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Oren Bar-Gill

2016-01-01

Full Text Available Objective to study the procedure of exiting the contract its costs and benefits. Methods statistical method comparative analysis. Results free exit from contract is one of the most powerful tools for the consumer rights protection. The procedure frees consumers from bad deals and keeps businesses honest. Yet consumers often choose transactions with lockin provisions trading off exit rights for other perks. This article examines the costs and benefits of free exit as compared to the lockin alternative. According to the authors the present regulation of exit penalties in the USA is poorly tailored to address concerns about lockin particularly in light of increasingly ubiquitous marketbased solutions. The article also calls regulatory attention to loyalty rewards which are shown to be as powerful as exit penalties and equally detrimental. Scientific novelty the article reveals a paradoxical state of the law exit regulations in the USA are used most where they are needed least. Termination penalties present an obvishyous target for regulatory intervention while loyalty programs seem benign not warranting any regulatory attention. Practical significance the article is of interest for the Russian juridical science and lawmaking authorities as in Russia the issue of exiting the contract is as topical as in the USA and requires solution which would impair neither the rights of consumers nor the rights of the sellers ofnbspproducts and services. nbsp

A balance of FGF and BMP signals regulates cell cycle exit and Equarin expression in lens cells

Science.gov (United States)

Jarrin, Miguel; Pandit, Tanushree; Gunhaga, Lena

2012-01-01

In embryonic and adult lenses, a balance of cell proliferation, cell cycle exit, and differentiation is necessary to maintain physical function. The molecular mechanisms regulating the transition of proliferating lens epithelial cells to differentiated primary lens fiber cells are poorly characterized. To investigate this question, we used gain- and loss-of-function analyses to modulate fibroblast growth factor (FGF) and/or bone morphogenetic protein (BMP) signals in chick lens/retina explants. Here we show that FGF activity plays a key role for proliferation independent of BMP signals. Moreover, a balance of FGF and BMP signals regulates cell cycle exit and the expression of Ccdc80 (also called Equarin), which is expressed at sites where differentiation of lens fiber cells occurs. BMP activity promotes cell cycle exit and induces Equarin expression in an FGF-dependent manner. In contrast, FGF activity is required but not sufficient to induce cell cycle exit or Equarin expression. Furthermore, our results show that in the absence of BMP activity, lens cells have increased cell cycle length or are arrested in the cell cycle, which leads to decreased cell cycle exit. Taken together, these findings suggest that proliferation, cell cycle exit, and early differentiation of primary lens fiber cells are regulated by counterbalancing BMP and FGF signals. PMID:22718906

The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

Directory of Open Access Journals (Sweden)

Anna Kirjavainen

2015-03-01

Full Text Available Hair cells of the organ of Corti (OC of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC, a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.

Airport exit and entry screening for Ebola--August-November 10, 2014.

Science.gov (United States)

Brown, Clive M; Aranas, Aaron E; Benenson, Gabrielle A; Brunette, Gary; Cetron, Marty; Chen, Tai-Ho; Cohen, Nicole J; Diaz, Pam; Haber, Yonat; Hale, Christa R; Holton, Kelly; Kohl, Katrin; Le, Amanda W; Palumbo, Gabriel J; Pearson, Kate; Phares, Christina R; Alvarado-Ramy, Francisco; Roohi, Shah; Rotz, Lisa D; Tappero, Jordan; Washburn, Faith M; Watkins, James; Pesik, Nicki

2014-12-12

In response to the largest recognized Ebola virus disease epidemic now occurring in West Africa, the governments of affected countries, CDC, the World Health Organization (WHO), and other international organizations have collaborated to implement strategies to control spread of the virus. One strategy recommended by WHO calls for countries with Ebola transmission to screen all persons exiting the country for "unexplained febrile illness consistent with potential Ebola infection." Exit screening at points of departure is intended to reduce the likelihood of international spread of the virus. To initiate this strategy, CDC, WHO, and other global partners were invited by the ministries of health of Guinea, Liberia, and Sierra Leone to assist them in developing and implementing exit screening procedures. Since the program began in August 2014, an estimated 80,000 travelers, of whom approximately 12,000 were en route to the United States, have departed by air from the three countries with Ebola transmission. Procedures were implemented to deny boarding to ill travelers and persons who reported a high risk for exposure to Ebola; no international air traveler from these countries has been reported as symptomatic with Ebola during travel since these procedures were implemented.

The RNA-binding protein Spo5 promotes meiosis II by regulating cyclin Cdc13 in fission yeast.

Science.gov (United States)

Arata, Mayumi; Sato, Masamitsu; Yamashita, Akira; Yamamoto, Masayuki

2014-03-01

Meiosis comprises two consecutive nuclear divisions, meiosis I and II. Despite this unique progression through the cell cycle, little is known about the mechanisms controlling the sequential divisions. In this study, we carried out a genetic screen to identify factors that regulate the initiation of meiosis II in the fission yeast Schizosaccharomyces pombe. We identified mutants deficient in meiosis II progression and repeatedly isolated mutants defective in spo5, which encodes an RNA-binding protein. Using fluorescence microscopy to visualize YFP-tagged protein, we found that spo5 mutant cells precociously lost Cdc13, the major B-type cyclin in fission yeast, before meiosis II. Importantly, the defect in meiosis II was rescued by increasing CDK activity. In wild-type cells, cdc13 transcripts increased during meiosis II, but this increase in cdc13 expression was weaker in spo5 mutants. Thus, Spo5 is a novel regulator of meiosis II that controls the level of cdc13 expression and promotes de novo synthesis of Cdc13. We previously reported that inhibition of Cdc13 degradation is necessary to initiate meiosis II; together with the previous information, the current findings indicate that the dual control of Cdc13 by de novo synthesis and suppression of proteolysis ensures the progression of meiosis II. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Repressive histone methylation regulates cardiac myocyte cell cycle exit.

Science.gov (United States)

El-Nachef, Danny; Oyama, Kyohei; Wu, Yun-Yu; Freeman, Miles; Zhang, Yiqiang; Robb MacLellan, W

2018-05-22

Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D. Although H3K9me3 is found across the genome, its loss in CMs preferentially disrupts cell cycle gene silencing. KDM4D binds directly to cell cycle genes and reduces H3K9me3 levels at these promotors. Loss of H3K9me3 preferentially leads to increased cell cycle gene expression resulting in enhanced CM cycling. Heart mass was increased in KDM4D overexpressing mice by postnatal day 14 (P14) and continued to increase until 9-weeks of age. ACM number, but not size, was significantly increased in KDM4D expressing hearts, suggesting CM hyperplasia accounts for the increased heart mass. Inducing KDM4D after normal development specifically in ACMs resulted in increased cell cycle gene expression and cycling. We demonstrated that H3K9me3 is required for CM cell cycle exit and terminal differentiation in ACMs. Depletion of H3K9me3 in adult hearts prevents and reverses permanent cell cycle exit and allows hyperplastic growth in adult hearts in vivo. Copyright © 2017. Published by Elsevier Ltd.

Sequence Classification: 890890 [

Lifescience Database Archive (English)

Full Text Available lar protein of unknown function, positive regulator of exit from mitosis; involved in regulating the release of Cdc14p from the nucle...olus in early anaphase; proposed to play similar role in meiosis; Spo12p || http://www.ncbi.nlm.nih.gov/protein/6321946 ...

Fission Yeast Apc15 Stabilizes MCC-Cdc20-APC/C Complexes, Ensuring Efficient Cdc20 Ubiquitination and Checkpoint Arrest.

Science.gov (United States)

May, Karen M; Paldi, Flora; Hardwick, Kevin G

2017-04-24

During mitosis, cells must segregate the replicated copies of their genome to their daughter cells with extremely high fidelity. Segregation errors lead to an abnormal chromosome number (aneuploidy), which typically results in disease or cell death [1]. Chromosome segregation and anaphase onset are initiated through the action of the multi-subunit E3 ubiquitin ligase known as the anaphase-promoting complex or cyclosome (APC/C [2]). The APC/C is inhibited by the spindle checkpoint in the presence of kinetochore attachment defects [3, 4]. Here we demonstrate that two non-essential APC/C subunits (Apc14 and Apc15) regulate association of spindle checkpoint proteins, in the form of the mitotic checkpoint complex (MCC), with the APC/C. apc14Δ mutants display increased MCC association with the APC/C and are unable to silence the checkpoint efficiently. Conversely, apc15Δ mutants display reduced association between the MCC and APC/C, are defective in poly-ubiquitination of Cdc20, and are checkpoint defective. In vitro reconstitution studies have shown that human MCC-APC/C can contain two molecules of Cdc20 [5-7]. Using a yeast strain expressing two Cdc20 genes with different epitope tags, we show by co-immunoprecipitation that this is true in vivo. MCC binding to the second molecule of Cdc20 is mediated via the C-terminal KEN box in Mad3. Somewhat surprisingly, complexes containing both molecules of Cdc20 accumulate in apc15Δ cells, and the implications of this observation are discussed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

29 CFR 1917.122 - Employee exits.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Employee exits. 1917.122 Section 1917.122 Labor Regulations...) MARINE TERMINALS Terminal Facilities § 1917.122 Employee exits. (a) Employee exits shall be clearly marked. (b) If an employee exit is not visible from employees' work stations, directional signs...

Synapse Formation in Monosynaptic Sensory–Motor Connections Is Regulated by Presynaptic Rho GTPase Cdc42

Science.gov (United States)

Imai, Fumiyasu; Ladle, David R.; Leslie, Jennifer R.; Duan, Xin; Rizvi, Tilat A.; Ciraolo, Georgianne M.; Zheng, Yi

2016-01-01

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic sensory–motor circuits in these mutants. Temporally targeted deletion of Cdc42 in sensory neurons after sensory–motor circuit establishment reveals that Cdc42 does not affect synaptic transmission. Furthermore, addition of the synaptic organizers, neuroligins, induces presynaptic differentiation of wild-type, but not Cdc42-deficient, proprioceptive sensory neurons in vitro. Together, our findings demonstrate that Cdc42 in presynaptic neurons is required for synapse formation in monosynaptic sensory–motor circuits. SIGNIFICANCE STATEMENT Group Ia proprioceptive sensory neurons form direct synapses with motor neurons, but the molecular mechanisms underlying synapse formation in these monosynaptic sensory–motor connections are unknown. We show that deleting Cdc42 in sensory neurons does not affect proprioceptive sensory axon targeting because axons reach the ventral spinal cord appropriately, but these neurons form significantly fewer presynaptic terminals on motor neurons. Electrophysiological analysis further shows that EPSPs are decreased in these mice. Finally, we demonstrate that Cdc42 is involved in neuroligin-dependent presynaptic differentiation of proprioceptive sensory neurons in vitro

Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

OpenAIRE

Wang, Zhihui; Trope, Claes G; Fl?renes, Vivi Ann; Suo, Zhenhe; Nesland, Jahn M; Holm, Ruth

2010-01-01

Background CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined. ...

The Hsk1(Cdc7) Replication Kinase Regulates Origin Efficiency

OpenAIRE

Patel, Prasanta K.; Kommajosyula, Naveen; Rosebrock, Adam; Bensimon, Aaron; Leatherwood, Janet; Bechhoefer, John; Rhind, Nicholas

2008-01-01

Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or ...

The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis.

Science.gov (United States)

Lee, Sun Joo; Rodriguez-Bravo, Veronica; Kim, Hyunjung; Datta, Sutirtha; Foley, Emily A

2017-05-15

PP2A comprising B56 regulatory subunit isoforms (PP2A B56 ) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2A B56 both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing APC/C (APC/C Cdc20 ), which is an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/C Cdc20 inhibitor formed at unattached kinetochores through SAC signaling. In contrast to this prediction, we show that depletion of B56 subunits does not increase the amount or stability of the MCC. Rather, delays in APC/C Cdc20 activation in B56-depleted cells correlate with impaired Cdc20 binding to APC/C. Stimulation of APC/C Cdc20 assembly does not require binding between PP2A B56 and BubR1, and thus this contribution of PP2A B56 towards mitotic exit is distinct from its functions at kinetochores. PP2A B56 associates with APC/C constitutively in a BubR1-independent manner. A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2A B56 , modulates APC/C Cdc20 assembly. These results elucidate the contributions of PP2A B56 towards completion of mitosis. © 2017. Published by The Company of Biologists Ltd.

Estrogen and Resveratrol Regulate Rac and Cdc42 Signaling to the Actin Cytoskeleton of Metastatic Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Nicolas G. Azios

2007-02-01

Full Text Available Estrogen and structurally related molecules play critical roles in breast cancer. We reported that resveratrol (50 µM, an estrogen-like phytosterol from grapes, acts in an antiestrogenic manner in breast cancer cells to reduce cell migration and to induce a global and sustained extension of actin structures called filopodia. Herein, we report that resveratrol-induced filopodia formation is time-dependent and concentration-dependent. In contrast to resveratrol at 50 µM, resveratrol at 5 µM acts in a manner similar to estrogen by increasing lamellipodia, as well as cell migration and invasion. Because Rho GTPases regulate the extension of actin structures, we investigated a role for Rac and Cdc42 in estrogen and resveratrol signaling. Our results demonstrate that 50 µM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 µM resveratrol increase Rac activity in breast cancer cells. MDA-MB-231 cells expressing dominant-negative Cdc42 or dominantnegative Rac retain filopodia response to 50 µM resveratrol. Lamellipodia response to 5 µM resveratrol, estrogen, or epidermal growth factor is inhibited in cells expressing dominant-negative Rac, indicating that Rac regulates estrogen and resveratrol (5 µM signaling to the actin cytoskeleton. These results indicate that signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42.

14 CFR 135.129 - Exit seating.

Science.gov (United States)

2010-01-01

... emergency evacuation provided by the certificate holder in printed or graphic form or the ability to... accordance with this section. (d) Each certificate holder shall include on passenger information cards.... (e) Each certificate holder shall include on passenger information cards, at each exit seat— (1) In...

14 CFR 121.585 - Exit seating.

Science.gov (United States)

2010-01-01

... section and related to emergency evacuation provided by the certificate holder in printed or graphic form... include on passenger information cards, presented in the language in which briefings and oral commands are... passenger information cards, at each exit seat— (1) In the primary language in which emergency commands are...

cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior

Directory of Open Access Journals (Sweden)

Sangmi Oh

2016-12-01

Full Text Available Cell division cycle 25 (cdc25 is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells.

Cdc7 kinase - a new target for drug development.

Science.gov (United States)

Swords, Ronan; Mahalingam, Devalingam; O'Dwyer, Michael; Santocanale, Corrado; Kelly, Kevin; Carew, Jennifer; Giles, Francis

2010-01-01

The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.

The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis

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Hartley Rebecca S

2010-01-01

Full Text Available Abstract Background The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Results Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4α and xCdc4β. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. Conclusions We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.

14 CFR 23.805 - Flightcrew emergency exits.

Science.gov (United States)

2010-01-01

... emergency exit must be located to allow rapid evacuation of the crew and have a size and shape of at least a... than six feet from the ground, an assisting means must be provided. The assisting means may be a rope...

Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

Directory of Open Access Journals (Sweden)

Kelly E Roney

Full Text Available Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/- macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/- macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.

Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216 in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

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Flørenes Vivi

2010-05-01

Full Text Available Abstract Background CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined. Methods Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho-CDC25C (Ser216 were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies. Results High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216 expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216. In univariate analysis, high expression of phospho-CDC25C (Ser216 was correlated with poor disease-specific survival (p = 0.04. However, such an association was annulled in multivariate analysis. Conclusions Our results suggest that CDC25C and phospho-CDC25C (Ser216 play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216 were associated with

Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

International Nuclear Information System (INIS)

Wang, Zhihui; Trope, Claes G; Flørenes, Vivi Ann; Suo, Zhenhe; Nesland, Jahn M; Holm, Ruth

2010-01-01

CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined. Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho)-CDC25C (Ser216) were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies. High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216) expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216). In univariate analysis, high expression of phospho-CDC25C (Ser216) was correlated with poor disease-specific survival (p = 0.04). However, such an association was annulled in multivariate analysis. Our results suggest that CDC25C and phospho-CDC25C (Ser216) play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216) were associated with malignant features and aggressive cancer phenotypes. However, the

Role of AtCDC48 & the AtCDC48 Regulatory Protein Family, PUX, in Plant Cell Morphogenesis

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Bednarek, Sebastian, Y.

2009-11-08

The long-term objective of this work is to understand the molecular events and mechanisms involved in secretory membrane trafficking and organelle biogenesis, which are crucial for normal plant growth and development. Our studies have suggested a vital role for the cytosolic chaperone Cdc48p/p97 during cytokinesis and cell expansion which are highly dependent upon secretory membrane trafficking. Localization studies have shown that the plant Cdc48p/p97, AtCDC48, and the Arabidopsis ortholog of the ER- and Golgi-associated SNARE, syntaxin 5, (referred to as SYP31) are targeted to the division plane during cytokinesis. In addition, AtCDC48 and SYP31 were shown to interact in vitro and in vivo. To characterize further the function of AtCDC48 and SYP31 we have utilized affinity chromatography and MALDI-MS to identify several plant-specific proteins that interact with SYP31 and/or modulate the activity of AtCDC48 including two UBX (i.e. ubiquitin-like) domain containing proteins, PUX1 and PUX2 (Proteins containing UBX domain). These proteins define a plant protein family consisting of 15 uncharacterized members that we postulate interact with AtCDC48. Biochemical studies have demonstrated that PUX2 is a novel membrane adapter for AtCDC48 that mediates AtCDC48/SYP31 interaction and is likely to control AtCDC48-dependent membrane fusion. In contrast, PUX1 negatively regulates AtCDC48 by inhibiting its ATPase activity and by promoting the disassembly of the active hexamer. These findings provide the first evidence that the assembly and disassembly of the CDC48/p97complex is actually a dynamic process. This new unexpected level of regulation for CDC48/p97 was demonstrated to be critical in vivo as pux1 loss-of-function mutants grow faster than wild-type plants. These studies suggest a role for AtCDC48 in plant cell cycle progression including cytokinesis and/or cell expansion. The proposed studies are designed to: 1) characterize further the localization and function of AtCDC

Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism

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Foe, Ian T.; Foster, Scott A.; Cheung, Stephanie K.; DeLuca, Steven Z.; Morgan, David O.; Toczyski, David P.

2012-01-01

SUMMARY Background Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the Anaphase Promoting Complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood. Results Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule, but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20’s C-box. Cdc20 turnover by this intramolecular mechanism is cell cycle-regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination. Conclusion We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle. PMID:22079111

Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin

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Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine

2006-01-01

for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of beta-catenin. In the absence of Cdc42, degradation of beta-catenin was increased corresponding to a decreased phosphorylation of GSK3beta at Ser 9 and an increased phosphorylation of axin, which is known to be required...... for binding of beta-catenin to the degradation machinery. Cdc42-mediated regulation of beta-catenin turnover was completely dependent on PKCzeta, which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of beta-catenin turnover is important for terminal differentiation of HF...

A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis.

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Takashi K Ito

Full Text Available Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-κB signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-κB suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses.

The Hsk1(Cdc7) replication kinase regulates origin efficiency.

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Patel, Prasanta K; Kommajosyula, Naveen; Rosebrock, Adam; Bensimon, Aaron; Leatherwood, Janet; Bechhoefer, John; Rhind, Nicholas

2008-12-01

Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency.

The Hsk1(Cdc7) Replication Kinase Regulates Origin Efficiency

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Patel, Prasanta K.; Kommajosyula, Naveen; Rosebrock, Adam; Bensimon, Aaron; Leatherwood, Janet; Bechhoefer, John

2008-01-01

Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or decreasing Hsk1-Dfp1 levels correspondingly increases or decreases origin efficiency. Furthermore, tethering Hsk1-Dfp1 near an origin increases the efficiency of that origin, suggesting that the effective local concentration of Hsk1-Dfp1 regulates origin firing. Using photobleaching, we show that Hsk1-Dfp1 is freely diffusible in the nucleus. These results support a model in which the accessibility of replication origins to Hsk1-Dfp1 regulates origin efficiency and provides a potential mechanistic link between chromatin structure and replication timing. By manipulating Hsk1-Dfp1 levels, we show that increasing or decreasing origin firing rates leads to an increase in genomic instability, demonstrating the biological importance of appropriate origin efficiency. PMID:18799612

Cell cycle sibling rivalry: Cdc2 vs. Cdk2.

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Kaldis, Philipp; Aleem, Eiman

2005-11-01

It has been long believed that the cyclin-dependent kinase 2 (Cdk2) binds to cyclin E or cyclin A and exclusively promotes the G1/S phase transition and that Cdc2/cyclin B complexes play a major role in mitosis. We now provide evidence that Cdc2 binds to cyclin E (in addition to cyclin A and B) and is able to promote the G1/S transition. This new concept indicates that both Cdk2 and/or Cdc2 can drive cells through G1/S phase in parallel. In this review we discuss the classic cell cycle model and how results from knockout mice provide new evidence that refute this model. We focus on the roles of Cdc2 and p27 in regulating the mammalian cell cycle and propose a new model for cell cycle regulation that accommodates these novel findings.

Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

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Schulz, Anna M; Stutte, Susanne; Hogl, Sebastian

2015-01-01

Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 defici...

miRNA-497 Negatively Regulates the Growth and Motility of Chondrosarcoma Cells by Targeting Cdc25A.

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Lu, Yandong; Li, Fangguo; Xu, Tao; Sun, Jie

2016-01-01

Chondrosarcoma (CHS) is the second most common malignant bone sarcoma with increased risk of invasion and metastasis. However, the regulatory mechanisms of CHS tumorigenesis remain unknown. Here we investigated the novel role of miR-497 in regulating chondrosarcoma cell growth and cell cycle arrest. RT-PCR analysis showed that the expression of miR-497 is aberrantly downregulated in human chondrosarcoma samples and cells. After transfection with miR-497 mimic or antagomir, the proliferation and apoptosis of JJ012 and OUMS-27 chondrosarcoma cells were determined by CCK-8 assay and flow cytometric analysis, respectively. Results showed that the proliferation capacity of JJ012 and OUMS-27 cells was significantly decreased by miR-497 overexpression but increased by miR-497 repression. Apoptosis in both cell types was remarkably enhanced by miR-497 mimic but inhibited by miR-497 antagomir. By bioinformatics and luciferase reporter analysis, Cdc25A was proven to be a direct target of miR-497 in chondrosarcoma cells. Further studies indicated that miR-497 modulates the growth of chondrosarcoma cells by targeting Cdc25A, in which the cell cycle inhibitor p21 is involved through a p53-independent pathway. In conclusion, we demonstrated that miR-497 represents a potential tumor suppressor in human chondrosarcoma that regulates the growth of chondrosarcoma cells by targeting Cdc25A. This may provide a novel therapeutic target for chondrosarcoma.

SU-F-T-675: Down-Regulating the Expression of Cdc42 and Inhibition of Migration of A549 with Combined Treatment of Ionizing Radiation and Sevoflurane

International Nuclear Information System (INIS)

Feng, Y; Feng, J; Huang, Z

2016-01-01

Purpose: Cdc42 is involved in cell transformation, proliferation, invasion and metastasis of human cancer cells. Cdc42 overexpression has been reported in several types of cancers. This study investigated the combined treatment effects of ionizing radiation and sevoflurane on down-regulating Cdc42 expression and suppressing migration of human adenocarcinoma cell line A549. Methods: Samples of A549 cells with Cdc42 overexpression were created and Cdc42 expression was determined by Western blotting. Increase of migration speed by Cdc42-HA overexpression was confirmed with an initial in-vitro scratch assay. The cells grown in culture media were separated into 2 groups of 6 samples: one for the control and the other was treated with 4% sevoflurane for 5hrs prior to a single-fraction radiation of 4Gy using a 6MV beam. Cell migration speeds of the 2 groups were measured with an initial in-vitro scratch assay. The scratch was created with a pipette tip immediately after treatment and images at 4 post-treatment time points (0h, 3h, 6h, 12h) were acquired. The distance between the two separated sides at 0h was used as reference and subsequent changes of the distance over time was defined as the cell migration speed. Image processing and measurement were performed with an in-house software. The experiment was repeated three times independently to evaluate the repeatability and reliability. Statistical analysis was performed with SPSS 19.0. Results: Western blotting showed the treatment down-regulated Cdc42 overexpression. Quantitative analysis and two-tailed t-test showed that cell migration speed of the treated group was higher than the control group at all time points after treatment (p < 0.02). Conclusion: Combined treatment of 6MV photon and sevoflurane can cause the effects of down-regulating Cdc42 overexpression and decrease of migration speed of A549 cells which provides potential of clinical benefit for the cancer therapy. More investigation is needed to further

SU-F-T-675: Down-Regulating the Expression of Cdc42 and Inhibition of Migration of A549 with Combined Treatment of Ionizing Radiation and Sevoflurane

Energy Technology Data Exchange (ETDEWEB)

Feng, Y [East Carolina University, Greenville, NC (United States); Feng, J [Tianjin University, Tianjin (China); Huang, Z [East Carolina University, Greenville, NC (United States)

2016-06-15

Purpose: Cdc42 is involved in cell transformation, proliferation, invasion and metastasis of human cancer cells. Cdc42 overexpression has been reported in several types of cancers. This study investigated the combined treatment effects of ionizing radiation and sevoflurane on down-regulating Cdc42 expression and suppressing migration of human adenocarcinoma cell line A549. Methods: Samples of A549 cells with Cdc42 overexpression were created and Cdc42 expression was determined by Western blotting. Increase of migration speed by Cdc42-HA overexpression was confirmed with an initial in-vitro scratch assay. The cells grown in culture media were separated into 2 groups of 6 samples: one for the control and the other was treated with 4% sevoflurane for 5hrs prior to a single-fraction radiation of 4Gy using a 6MV beam. Cell migration speeds of the 2 groups were measured with an initial in-vitro scratch assay. The scratch was created with a pipette tip immediately after treatment and images at 4 post-treatment time points (0h, 3h, 6h, 12h) were acquired. The distance between the two separated sides at 0h was used as reference and subsequent changes of the distance over time was defined as the cell migration speed. Image processing and measurement were performed with an in-house software. The experiment was repeated three times independently to evaluate the repeatability and reliability. Statistical analysis was performed with SPSS 19.0. Results: Western blotting showed the treatment down-regulated Cdc42 overexpression. Quantitative analysis and two-tailed t-test showed that cell migration speed of the treated group was higher than the control group at all time points after treatment (p < 0.02). Conclusion: Combined treatment of 6MV photon and sevoflurane can cause the effects of down-regulating Cdc42 overexpression and decrease of migration speed of A549 cells which provides potential of clinical benefit for the cancer therapy. More investigation is needed to further

Cdc42 regulates cofilin during the establishment of neuronal polarity

DEFF Research Database (Denmark)

Garvalov, Boyan K; Flynn, Kevin C; Neukirchen, Dorothee

2007-01-01

suppressed ability to form axons both in vivo and in culture. This was accompanied by disrupted cytoskeletal organization, enlargement of the growth cones, and inhibition of filopodial dynamics. Axon formation in the knock-out neurons was rescued by manipulation of the actin cytoskeleton, indicating...... that the effects of Cdc42 ablation are exerted through modulation of actin dynamics. In addition, the knock-outs showed a specific increase in the phosphorylation (inactivation) of the Cdc42 effector cofilin. Furthermore, the active, nonphosphorylated form of cofilin was enriched in the axonal growth cones of wild...

Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas.

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Butz, Henriett; Németh, Kinga; Czenke, Dóra; Likó, István; Czirják, Sándor; Zivkovic, Vladimir; Baghy, Kornélia; Korbonits, Márta; Kovalszky, Ilona; Igaz, Péter; Rácz, Károly; Patócs, Attila

2017-07-01

Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/M transition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement. Totally, 80 NFPA and 14 normal pituitary (NP) tissues were examined. Expression of 46 genes encoding members of the G2/M transition was profiled on 34 NFPA and 10 NP samples on TaqMan Low Density Array. Expression of CDC25A and two miRNAs targeting CDC25A were validated by individual quantitative real time PCR using TaqMan assays. Protein expression of CDC25A, CDC25C, CDK1 and phospho-CDK1 (Tyr-15) was investigated on tissue microarray and immunohistochemistry. Several genes' expression alteration were observed in NFPA compared to normal tissues by transcription profiling. On protein level CDC25A and both the total and the phospho-CDK1 were overexpressed in adenoma tissues. CDC25A correlated with nuclear localized CDK1 (nCDK1) and with tumor size and nCDK1 with Ki-67 index. Comparing primary vs. recurrent adenomas we found that Ki-67 proliferation index was higher and phospho-CDK1 (inactive form) was downregulated in recurrent tumors compared to primary adenomas. Investigating the potential causes behind CDC25A overexpression we could not find copy number variation at the coding region nor expression alteration of CDC25A regulating transcription factors however CDC25A targeting miRNAs were downregulated in NFPA and negatively correlated with CDC25A expression. Our results suggest that among alterations of G2/M transition of the cell cycle, overexpression of the CDK1 and CDC25A may have a role in the pathogenesis of the NFPA and that CDC25A is potentially

ORACLS- OPTIMAL REGULATOR ALGORITHMS FOR THE CONTROL OF LINEAR SYSTEMS (CDC VERSION)

Science.gov (United States)

Armstrong, E. S.

1994-01-01

This control theory design package, called Optimal Regulator Algorithms for the Control of Linear Systems (ORACLS), was developed to aid in the design of controllers and optimal filters for systems which can be modeled by linear, time-invariant differential and difference equations. Optimal linear quadratic regulator theory, currently referred to as the Linear-Quadratic-Gaussian (LQG) problem, has become the most widely accepted method of determining optimal control policy. Within this theory, the infinite duration time-invariant problems, which lead to constant gain feedback control laws and constant Kalman-Bucy filter gains for reconstruction of the system state, exhibit high tractability and potential ease of implementation. A variety of new and efficient methods in the field of numerical linear algebra have been combined into the ORACLS program, which provides for the solution to time-invariant continuous or discrete LQG problems. The ORACLS package is particularly attractive to the control system designer because it provides a rigorous tool for dealing with multi-input and multi-output dynamic systems in both continuous and discrete form. The ORACLS programming system is a collection of subroutines which can be used to formulate, manipulate, and solve various LQG design problems. The ORACLS program is constructed in a manner which permits the user to maintain considerable flexibility at each operational state. This flexibility is accomplished by providing primary operations, analysis of linear time-invariant systems, and control synthesis based on LQG methodology. The input-output routines handle the reading and writing of numerical matrices, printing heading information, and accumulating output information. The basic vector-matrix operations include addition, subtraction, multiplication, equation, norm construction, tracing, transposition, scaling, juxtaposition, and construction of null and identity matrices. The analysis routines provide for the following

Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice

DEFF Research Database (Denmark)

Yuan, Haixin; Zhang, Hong; Wu, Xunwei

2009-01-01

Cdc42, a member of the Rho guanosine triphosphatase (GTPase) family, plays important roles in the regulation of the cytoskeleton, cell proliferation, cell polarity, and cellular transport, but little is known about its specific function in mammalian liver. We investigated the function of Cdc42...... in regulating liver regeneration. Using a mouse model with liver-specific knockout of Cdc42 (Cdc42LK), we studied liver regeneration after partial hepatectomy. Histological analysis, immunostaining, and western blot analysis were performed to characterize Cdc42LK livers and to explore the role of Cdc42 in liver...... regeneration. In control mouse livers, Cdc42 became activated between 3 and 24 hours after partial hepatectomy. Loss of Cdc42 led to a significant delay of liver recovery after partial hepatectomy, which was associated with reduced and delayed DNA synthesis indicated by 5-bromo-2'-deoxyuridine staining...

Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis

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Moore Finola E

2009-07-01

Full Text Available Abstract The execution of the mitotic program with high fidelity is dependent upon precise spatiotemporal regulation of posttranslational protein modifications. For example, the timely polyubiquitination of critical mitotic regulators by Anaphase Promoting Complex/Cyclosome (APC/C is essential for the metaphase to anaphase transition and mitotic exit. The spindle assembly checkpoint prevents unscheduled activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of kinetochores to mitotic spindle and facilitating equal segregation of sister chromatids. The critical effector of the spindle checkpoint, Mitotic arrest deficient 2 (Mad2, is recruited to unattached kinetochores forming a complex with other regulatory proteins to efficiently and cooperatively inhibit APC/C-Cdc20. A weakened and/or dysfunctional spindle checkpoint has been linked to the development of genomic instability in both cell culture and animal models, and evidence suggests that aberrant regulation of the spindle checkpoint plays a critical role in human carcinogenesis. Recent studies have illuminated a network of both degradative and non-degradative ubiquitination events that regulate the metaphase to anaphase transition and mitotic exit. Within this context, our recent work showed that the HECT (Homologous to E6-AP C-terminus-family E3 ligase Smurf2 (Smad specific ubiquitin regulatory factor 2, known as a negative regulator of transforming growth factor-beta (TGF-β signaling, is required for a functional spindle checkpoint by promoting the functional localization and stability of Mad2. Here we discuss putative models explaining the role of Smurf2 as a new regulator in the spindle checkpoint. The dynamic mitotic localization of Smurf2 to the centrosome and other critical mitotic structures provides implications about mitotic checkpoint control dependent on various ubiquitination events. Finally, deregulated Smurf2 activity may contribute to carcinogenesis by

Two Cdc2 Kinase Genes with Distinct Functions in Vegetative and Infectious Hyphae in Fusarium graminearum.

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Huiquan Liu

2015-06-01

Full Text Available Eukaryotic cell cycle involves a number of protein kinases important for the onset and progression through mitosis, most of which are well characterized in the budding and fission yeasts and conserved in other fungi. However, unlike the model yeast and filamentous fungi that have a single Cdc2 essential for cell cycle progression, the wheat scab fungus Fusarium graminearum contains two CDC2 orthologs. The cdc2A and cdc2B mutants had no obvious defects in growth rate and conidiation but deletion of both of them is lethal, indicating that these two CDC2 orthologs have redundant functions during vegetative growth and asexual reproduction. However, whereas the cdc2B mutant was normal, the cdc2A mutant was significantly reduced in virulence and rarely produced ascospores. Although deletion of CDC2A had no obvious effect on the formation of penetration branches or hyphopodia, the cdc2A mutant was limited in the differentiation and growth of infectious growth in wheat tissues. Therefore, CDC2A plays stage-specific roles in cell cycle regulation during infectious growth and sexual reproduction. Both CDC2A and CDC2B are constitutively expressed but only CDC2A was up-regulated during plant infection and ascosporogenesis. Localization of Cdc2A- GFP to the nucleus but not Cdc2B-GFP was observed in vegetative hyphae, ascospores, and infectious hyphae. Complementation assays with chimeric fusion constructs showed that both the N- and C-terminal regions of Cdc2A are important for its functions in pathogenesis and ascosporogenesis but only the N-terminal region is important for its subcellular localization. Among the Sordariomycetes, only three Fusarium species closely related to F. graminearum have two CDC2 genes. Furthermore, F. graminearum uniquely has two Aurora kinase genes and one additional putative cyclin gene, and its orthologs of CAK1 and other four essential mitotic kinases in the budding yeast are dispensable for viability. Overall, our data

Two Cdc2 Kinase Genes with Distinct Functions in Vegetative and Infectious Hyphae in Fusarium graminearum.

Science.gov (United States)

Liu, Huiquan; Zhang, Shijie; Ma, Jiwen; Dai, Yafeng; Li, Chaohui; Lyu, Xueliang; Wang, Chenfang; Xu, Jin-Rong

2015-06-01

Eukaryotic cell cycle involves a number of protein kinases important for the onset and progression through mitosis, most of which are well characterized in the budding and fission yeasts and conserved in other fungi. However, unlike the model yeast and filamentous fungi that have a single Cdc2 essential for cell cycle progression, the wheat scab fungus Fusarium graminearum contains two CDC2 orthologs. The cdc2A and cdc2B mutants had no obvious defects in growth rate and conidiation but deletion of both of them is lethal, indicating that these two CDC2 orthologs have redundant functions during vegetative growth and asexual reproduction. However, whereas the cdc2B mutant was normal, the cdc2A mutant was significantly reduced in virulence and rarely produced ascospores. Although deletion of CDC2A had no obvious effect on the formation of penetration branches or hyphopodia, the cdc2A mutant was limited in the differentiation and growth of infectious growth in wheat tissues. Therefore, CDC2A plays stage-specific roles in cell cycle regulation during infectious growth and sexual reproduction. Both CDC2A and CDC2B are constitutively expressed but only CDC2A was up-regulated during plant infection and ascosporogenesis. Localization of Cdc2A- GFP to the nucleus but not Cdc2B-GFP was observed in vegetative hyphae, ascospores, and infectious hyphae. Complementation assays with chimeric fusion constructs showed that both the N- and C-terminal regions of Cdc2A are important for its functions in pathogenesis and ascosporogenesis but only the N-terminal region is important for its subcellular localization. Among the Sordariomycetes, only three Fusarium species closely related to F. graminearum have two CDC2 genes. Furthermore, F. graminearum uniquely has two Aurora kinase genes and one additional putative cyclin gene, and its orthologs of CAK1 and other four essential mitotic kinases in the budding yeast are dispensable for viability. Overall, our data indicate that cell cycle

Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

International Nuclear Information System (INIS)

Kaellstroem, Helena; Lindqvist, Arne; Pospisil, Vitek; Lundgren, Andreas; Karlsson Rosenthal, Christina

2005-01-01

The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm

Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

Energy Technology Data Exchange (ETDEWEB)

Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

2015-06-15

Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

International Nuclear Information System (INIS)

Peng, Ting; Wang, Wei-Na; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

2015-01-01

Highlights: • Cd 2+ induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd 2+ . • DsRNA-suppression of LvCdc42 and MAPKs during Cd 2+ stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd 2+ stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd 2+ . They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses

Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.

Science.gov (United States)

Zeng, Canjun; Goodluck, Helen; Qin, Xuezhong; Liu, Bo; Mohan, Subburaman; Xing, Weirong

2016-10-01

Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment. Overexpression of constitutively active Q61L RAC1 partially rescued the resorptive function of Lrrk1-deficient osteoclasts. Furthermore, lack of Lrrk1 in osteoclasts led to reduced autophosphorylation of p21 protein-activated kinase-1 at Ser 144 , catalyzed by RAC1/Cdc42 binding and activation. Our data indicate that Lrrk1 regulates osteoclast function by directly modulating phosphorylation and activation of small GTPase RAC1/Cdc42 and that its function depends on ANK, ROC, WD40, and kinase domains. Copyright © 2016 the American Physiological Society.

Exit selection strategy in pedestrian evacuation simulation with multi-exits

International Nuclear Information System (INIS)

Yue Hao; Zhang Bin-Ya; Shao Chun-Fu; Xing Yan

2014-01-01

A mixed strategy of the exit selection in a pedestrian evacuation simulation with multi-exits is constructed by fusing the distance-based and time-based strategies through a cognitive coefficient, in order to reduce the evacuation imbalance caused by the asymmetry of exits or pedestrian layout, to find a critical density to distinguish whether the strategy of exit selection takes effect or not, and to analyze the exit selection results with different cognitive coefficients. The strategy of exit selection is embedded in the computation of the shortest estimated distance in a dynamic parameter model, in which the concept of a jam area layer and the procedure of step-by-step expending are introduced. Simulation results indicate the characteristics of evacuation time gradually varying against cognitive coefficient and the effectiveness of reducing evacuation imbalance caused by the asymmetry of pedestrian or exit layout. It is found that there is a critical density to distinguish whether a pedestrian jam occurs in the evacuation and whether an exit selection strategy is in effect. It is also shown that the strategy of exit selection has no effect on the evacuation process in the no-effect phase with a low density, and that evacuation time and exit selection are dependent on the cognitive coefficient and pedestrian initial density in the in-effect phase with a high density. (general)

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

Energy Technology Data Exchange (ETDEWEB)

Nagahama, Ryo [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Tanaka, Junichi [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aizawa, Ryo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Kassai, Hidetoshi [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Mishima, Kenji [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aiba, Atsu [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Maki, Koutaro [Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan)

2016-02-19

Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation.

Directory of Open Access Journals (Sweden)

Huzoor Akbar

Full Text Available Cdc42 and Rac1, members of the Rho family of small GTPases, play critical roles in actin cytoskeleton regulation. We have shown previously that Rac1 is involved in regulation of platelet secretion and aggregation. However, the role of Cdc42 in platelet activation remains controversial. This study was undertaken to better understand the role of Cdc42 in platelet activation.We utilized the Mx-cre;Cdc42(lox/lox inducible mice with transient Cdc42 deletion to investigate the involvement of Cdc42 in platelet function. The Cdc42-deficient mice exhibited a significantly reduced platelet count than the matching Cdc42(+/+ mice. Platelets isolated from Cdc42(-/-, as compared to Cdc42(+/+, mice exhibited (a diminished phosphorylation of PAK1/2, an effector molecule of Cdc42, (b inhibition of filopodia formation on immobilized CRP or fibrinogen, (c inhibition of CRP- or thrombin-induced secretion of ATP and release of P-selectin, (d inhibition of CRP, collagen or thrombin induced platelet aggregation, and (e minimal phosphorylation of Akt upon stimulation with CRP or thrombin. The bleeding times were significantly prolonged in Cdc42(-/- mice compared with Cdc42(+/+ mice.Our data demonstrate that Cdc42 is required for platelet filopodia formation, secretion and aggregation and therefore plays a critical role in platelet mediated hemostasis and thrombosis.

Raptor is phosphorylated by cdc2 during mitosis.

Directory of Open Access Journals (Sweden)

Dana M Gwinn

2010-02-01

Full Text Available The appropriate control of mitotic entry and exit is reliant on a series of interlocking signaling events that coordinately drive the biological processes required for accurate cell division. Overlaid onto these signals that promote orchestrated cell division are checkpoints that ensure appropriate mitotic spindle formation, a lack of DNA damage, kinetochore attachment, and that each daughter cell has the appropriate complement of DNA. We recently discovered that AMP-activated protein kinase (AMPK modulates the G2/M phase of cell cycle progression in part through its suppression of mammalian target of rapamycin (mTOR signaling. AMPK directly phosphorylates the critical mTOR binding partner raptor inhibiting mTORC1 (mTOR-raptor rapamycin sensitive mTOR kinase complex 1. As mTOR has been previously tied to mitotic control, we examined further how raptor may contribute to this process.We have discovered that raptor becomes highly phosphorylated in cells in mitosis. Utilizing tandem mass spectrometry, we identified a number of novel phosphorylation sites in raptor, and using phospho-specific antibodies demonstrated that raptor becomes phosphorylated on phospho-serine/threonine-proline sites in mitosis. A combination of site-directed mutagenesis in a tagged raptor cDNA and analysis with a series of new phospho-specific antibodies generated against different sites in raptor revealed that Serine 696 and Threonine 706 represent two key sites in raptor phosphorylated in mitosis. We demonstrate that the mitotic cyclin-dependent kinase cdc2/CDK1 is the kinase responsible for phosphorylating these sites, and its mitotic partner Cyclin B efficiently coimmunoprecipitates with raptor in mitotic cells.This study demonstrates that the key mTOR binding partner raptor is directly phosphorylated during mitosis by cdc2. This reinforces previous studies suggesting that mTOR activity is highly regulated and important for mitotic progression, and points to a direct

Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1

DEFF Research Database (Denmark)

Petersen, B O; Wagener, C; Marinoni, F

2000-01-01

is targeted for ubiquitin-mediated proteolysis by the anaphase promoting complex (APC)/cyclosome in G(1). A combination of point mutations in the destruction box and KEN-box motifs in CDC6 stabilizes the protein in G(1) and in quiescent cells. Furthermore, APC, in association with CDH1, ubiquitinates CDC6...... in vitro, and both APC and CDH1 are required and limiting for CDC6 proteolysis in vivo. Although a stable mutant of CDC6 is biologically active, overexpression of this mutant or wild-type CDC6 is not sufficient to induce multiple rounds of DNA replication in the same cell cycle. The APC-CDH1-dependent...

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

International Nuclear Information System (INIS)

Nagahama, Ryo; Yamada, Atsushi; Tanaka, Junichi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Yamamoto, Matsuo; Mishima, Kenji; Aiba, Atsu; Maki, Koutaro; Kamijo, Ryutaro

2016-01-01

Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 "f"l"/"f"l; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 "f"l"/"f"l) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

Cdc7-Dbf4 Regulates NDT80 Transcription as Well as Reductional Segregation during Budding Yeast Meiosis

OpenAIRE

Lo, Hsiao-Chi; Wan, Lihong; Rosebrock, Adam; Futcher, Bruce; Hollingsworth, Nancy M.

2008-01-01

In budding yeast, as in other eukaryotes, the Cdc7 protein kinase is important for initiation of DNA synthesis in vegetative cells. In addition, Cdc7 has crucial meiotic functions: it facilitates premeiotic DNA replication, and it is essential for the initiation of recombination. This work uses a chemical genetic approach to demonstrate that Cdc7 kinase has additional roles in meiosis. First, Cdc7 allows expression of NDT80, a meiosis-specific transcriptional activator required for the induct...

Characterization of cyclin-dependent kinases and Cdc2/Cdc28 kinase subunits in Trichomonas vaginalis.

Science.gov (United States)

Amador, Erick; López-Pacheco, Karla; Morales, Nataly; Coria, Roberto; López-Villaseñor, Imelda

2017-04-01

Cyclin-dependent kinases (CDKs) have important roles in regulating key checkpoints between stages of the cell cycle. Their activity is tightly regulated through a variety of mechanisms, including through binding with cyclin proteins and the Cdc2/Cdc28 kinase subunit (CKS), and their phosphorylation at specific amino acids. Studies of the components involved in cell cycle control in parasitic protozoa are limited. Trichomonas vaginalis is the causative agent of trichomoniasis in humans and is therefore important in public health; however, some of the basic biological processes used by this organism have not been defined. Here, we characterized proteins potentially involved in cell cycle regulation in T. vaginalis. Three genes encoding protein kinases were identified in the T. vaginalis genome, and the corresponding recombinant proteins (TvCRK1, TvCRK2, TvCRK5) were studied. These proteins displayed similar sequence features to CDKs. Two genes encoding CKSs were also identified, and the corresponding recombinant proteins were found to interact with TvCRK1 and TvCRK2 by a yeast two-hybrid system. One putative cyclin B protein from T. vaginalis was found to bind to and activate the kinase activities of TvCRK1 and TvCRK5, but not TvCRK2. This work is the first characterization of proteins involved in cell cycle control in T. vaginalis.

Cdc20 mediates D-box-dependent degradation of Sp100

International Nuclear Information System (INIS)

Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun; Ji, Chao-neng; Chen, Jin-zhong

2011-01-01

Highlights: ► Cdc20 is a co-activator of APC/C complex. ► Cdc20 recruits Sp100 and mediates its degradation. ► The D-box of Sp100 is required for Cdc20-mediated degradation. ► Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination.

Exit-strategies

DEFF Research Database (Denmark)

Mørck, Line Lerche; Palm, Anne-Mette; Sys Møller-Andersen, Camilla

different empirical sources. To develop and extend an "exit-prototype" about conditions of importance for moving beyond a gang/criminal position, we have analyzed documents (from newspapers and books), involved ex-gang members, social workers and experts as co-researchers in interviews, "gang......This paper is about exit-strategies, constructing a theoretical and empirical informed analysis of current societal conditions that influence motor cycle gangs such as Hells Angels or Bandidos and other ‘wild' youth' possibilities and limitations for moving beyond criminal activities. We especially...... focus on the involved communities in the current Danish gang-conflict, which escalated with deadly killings in 2008, and thereby became a so called "gang-war". We will start out presenting different practice notions of exit, and we will extend and discuss understandings of "exit-strategies" by analyzing...

Blastomyces dermatitidis septins CDC3, CDC10, and CDC12 impact the morphology of yeast and hyphae, but are not required for the phase transition.

Science.gov (United States)

Marty, Amber J; Gauthier, Gregory M

2013-01-01

Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.

Control of the mitotic exit network during meiosis

Science.gov (United States)

Attner, Michelle A.; Amon, Angelika

2012-01-01

The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to the timely exit from meiosis II. Consistent with a role for the MEN during meiosis II, we find that the signaling pathway is active only during meiosis II. Our analysis further shows that MEN signaling is modulated during meiosis in several key ways. Whereas binding of MEN components to spindle pole bodies (SPBs) is necessary for MEN signaling during mitosis, during meiosis MEN signaling occurs off SPBs and does not require the SPB recruitment factor Nud1. Furthermore, unlike during mitosis, MEN signaling is controlled through the regulated interaction between the MEN kinase Dbf20 and its activating subunit Mob1. Our data lead to the conclusion that a pathway essential for vegetative growth is largely dispensable for the specialized meiotic divisions and provide insights into how cell cycle regulatory pathways are modulated to accommodate different modes of cell division. PMID:22718910

The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast.

Directory of Open Access Journals (Sweden)

Richard C Silva

Full Text Available The Saccharomyces cerevisiae protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of YIH1 has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 in vivo and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a bona fide Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of YIH1 deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle.

The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

Energy Technology Data Exchange (ETDEWEB)

Sato, Mai [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Kitaguchi, Tetsuya [Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABOIS), Waseda University, 11 Biopolis Way, 05-01/02 Helios, Singapore 138667 (Singapore); Numano, Rika [The Electronics-Inspired Interdisciplinary Research Institute (EIIRIS), Toyohashi University of Technology, 1-1 Hibarigaoka, Tennpaku-cho, Toyohashi, Aichi 441-8580 (Japan); Ikematsu, Kazuya [Forensic Pathology and Science, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kakeyama, Masaki [Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033 (Japan); Murata, Masayuki; Sato, Ken [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan); Tsuboi, Takashi, E-mail: takatsuboi@bio.c.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902 (Japan)

2012-04-06

Highlights: Black-Right-Pointing-Pointer Regulation of exocytosis by Rho GTPase Cdc42. Black-Right-Pointing-Pointer Cdc42 increases the number of fusion events from newly recruited vesicles. Black-Right-Pointing-Pointer Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott-Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

International Nuclear Information System (INIS)

Sato, Mai; Kitaguchi, Tetsuya; Numano, Rika; Ikematsu, Kazuya; Kakeyama, Masaki; Murata, Masayuki; Sato, Ken; Tsuboi, Takashi

2012-01-01

Highlights: ► Regulation of exocytosis by Rho GTPase Cdc42. ► Cdc42 increases the number of fusion events from newly recruited vesicles. ► Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott–Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

Cdc20 mediates D-box-dependent degradation of Sp100

Energy Technology Data Exchange (ETDEWEB)

Wang, Ran; Li, Ke-min; Zhou, Cai-hong; Xue, Jing-lun [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Ji, Chao-neng, E-mail: Chnji@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China); Chen, Jin-zhong, E-mail: kingbellchen@fudan.edu.cn [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai (China)

2011-12-02

Highlights: Black-Right-Pointing-Pointer Cdc20 is a co-activator of APC/C complex. Black-Right-Pointing-Pointer Cdc20 recruits Sp100 and mediates its degradation. Black-Right-Pointing-Pointer The D-box of Sp100 is required for Cdc20-mediated degradation. Black-Right-Pointing-Pointer Sp100 expresses consistently at both the mRNA and protein levels in cell cycle. -- Abstract: Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand

C/EBP{delta} targets cyclin D1 for proteasome-mediated degradation via induction of CDC27/APC3 expression.

Science.gov (United States)

Pawar, Snehalata A; Sarkar, Tapasree Roy; Balamurugan, Kuppusamy; Sharan, Shikha; Wang, Jun; Zhang, Youhong; Dowdy, Steven F; Huang, A-Mei; Sterneck, Esta

2010-05-18

The transcription factor CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD, NFIL-6beta) has tumor suppressor function; however, the molecular mechanism(s) by which C/EBPdelta exerts its effect are largely unknown. Here, we report that C/EBPdelta induces expression of the Cdc27 (APC3) subunit of the anaphase promoting complex/cyclosome (APC/C), which results in the polyubiquitination and degradation of the prooncogenic cell cycle regulator cyclin D1, and also down-regulates cyclin B1, Skp2, and Plk-1. In C/EBPdelta knockout mouse embryo fibroblasts (MEF) Cdc27 levels were reduced, whereas cyclin D1 levels were increased even in the presence of activated GSK-3beta. Silencing of C/EBPdelta, Cdc27, or the APC/C coactivator Cdh1 (FZR1) in MCF-10A breast epithelial cells increased cyclin D1 protein expression. Like C/EBPdelta, and in contrast to cyclin D1, Cdc27 was down-regulated in several breast cancer cell lines, suggesting that Cdc27 itself may be a tumor suppressor. Cyclin D1 is a known substrate of polyubiquitination complex SKP1/CUL1/F-box (SCF), and our studies show that Cdc27 directs cyclin D1 to alternative degradation by APC/C. These findings shed light on the role and regulation of APC/C, which is critical for most cellular processes.

Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16/FoxO exit dauer.

Directory of Open Access Journals (Sweden)

Verena Gelmedin

Full Text Available Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3 in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370;daf-16(mu86 mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.

CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma.

Science.gov (United States)

Korpi-Hyövälti, Eeva; Cranston, Treena; Ryhänen, Eeva; Arola, Johanna; Aittomäki, Kristiina; Sane, Timo; Thakker, Rajesh V; Schalin-Jäntti, Camilla

2014-09-01

CDC73 mutations frequently underlie the hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. It has also been suggested that CDC73 deletion analysis should be performed in those patients without CDC73 mutations. To investigate for CDC73 deletion in a family with FIHP previously reported not to have CDC73 mutations. Eleven members (six affected with primary hyperparathyroidism and five unaffected) were ascertained from the family, and multiplex ligation-dependent probe amplification was performed to detect CDC73 deletion using leukocyte DNA. A previously unreported deletion of CDC73 involving exons 1-10 was detected in five affected members and two unaffected members who were 26 and 39 years of age. Two affected members had parathyroid carcinomas at the ages of 18 and 32 years, and they had Ki-67 proliferation indices of 5 and 14.5% and did not express parafibromin, encoded by CDC73. Primary hyperparathyroidism in the other affected members was due to adenomas and atypical adenomas, and none had jaw tumors. Two affected members had thoracic aortic aneurysms, which in one member occurred with parathyroid carcinoma and renal cysts. A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas. In addition, two affected males had thoracic aortic aneurysms, which may represent another associated clinical feature of this disorder.

Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts

International Nuclear Information System (INIS)

Appledorn, Daniel M; Dao, Kim-Hien T; O'Reilly, Sandra; Maher, Veronica M; McCormick, J Justin

2010-01-01

The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain. Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays. Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes, uPA and VEGF was further validated in both normoxic and hypoxic conditions. The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas transformed human cells, including their ability to form tumors in athymic

Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts

Directory of Open Access Journals (Sweden)

Dao Kim-Hien T

2010-01-01

Full Text Available Abstract Background The activities of Rac1 and Cdc42 are essential for HRas-induced transformation of rodent fibroblasts. What is more, expression of constitutively activated mutants of Rac1 and/or Cdc42 is sufficient for their malignant transformation. The role for these two Rho GTPases in HRas-mediated transformation of human fibroblasts has not been studied. Here we evaluated the contribution of Rac1 and Cdc42 to maintaining HRas-induced transformation of human fibroblasts, and determined the ability of constitutively activated mutants of Rac1 or Cdc42 to induce malignant transformation of a human fibroblast cell strain. Methods Under the control of a tetracycline regulatable promoter, dominant negative mutants of Rac1 and Cdc42 were expressed in a human HRas-transformed, tumor derived fibroblast cell line. These cells were used to determine the roles of Rac1 and/or Cdc42 proteins in maintaining HRas-induced transformed phenotypes. Similarly, constitutively active mutants were expressed in a non-transformed human fibroblast cell strain to evaluate their potential to induce malignant transformation. Affymetrix GeneChip arrays were used for transcriptome analyses, and observed expression differences were subsequently validated using protein assays. Results Expression of dominant negative Rac1 and/or Cdc42 significantly altered transformed phenotypes of HRas malignantly transformed human fibroblasts. In contrast, expression of constitutively active mutants of Rac1 or Cdc42 was not sufficient to induce malignant transformation. Microarray analysis revealed that the expression of 29 genes was dependent on Rac1 and Cdc42, many of which are known to play a role in cancer. The dependence of two such genes, uPA and VEGF was further validated in both normoxic and hypoxic conditions. Conclusion(s The results presented here indicate that expression of both Rac1 and Cdc42 is necessary for maintaining several transformed phenotypes in oncogenic HRas

Exit Prostitution

DEFF Research Database (Denmark)

Henriksen, Theresa Dyrvig; Aslaug Kjær, Agnete; Christensen, Gunvor

2015-01-01

Dette midtvejsnotat omhandler projektet ”Exit prostitution”. Exit-projektet blev påbegyndt i april 2012 og løber til udgangen af 2015 og befinder sig i øjeblikket midtvejs i projektets afprøvningsfase. I projektet anvendes metoden Critical Time Intervention (CTI), der er en evidensbaseret...... til det. Exit-projektet er dermed en central socialpolitisk indsats overfor borgere i prostitution i det danske samfund. I dette notat belyser vi midtvejsresultater for, hvordan udviklingen er for de borgere, der er nået halvt igennem et CTI-forløb. I den afsluttende evaluering af projektet i 2015 vil...

PPM1K Regulates Hematopoiesis and Leukemogenesis through CDC20-Mediated Ubiquitination of MEIS1 and p21

Directory of Open Access Journals (Sweden)

Xiaoye Liu

2018-05-01

Full Text Available Summary: In addition to acting as building blocks for biosynthesis, amino acids might serve as signaling regulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs. By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs, we could monitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20. PPM1K deficiency led to a notable decrease in MEIS1/p21 signaling to reduce the glycolysis and quiescence of HSCs, followed by a severe impairment in repopulation activities. Moreover, the deletion of Ppm1k dramatically extended survival in a murine leukemia model. These findings will enhance the current understanding of nutrient signaling in metabolism and function of stem cells. : Liu et al. show that the dynamics of BCAA metabolism in hematopoietic stem cells (HSCs and leukemia-initiating cells (LICs can be monitored by a genetically encoded fluorescent sensor. PPM1K promotes BCAA catabolism and maintains the glycolysis and quiescence of HSCs/LICs through the downregulation of CDC20-mediated ubiquitination of MEIS1 and p21. Keywords: branched-chain amino acids, PPM1K, ubiquitination, CDC20, MEIS1/p21, hematopoietic stem cells, leukemia-initiating cells

Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry

DEFF Research Database (Denmark)

Hein, Jamin B; Nilsson, Jakob

2016-01-01

Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during...... this window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2......, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation...

Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.

Science.gov (United States)

Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

2017-03-01

Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp ( Marsupenaeus japonicus ) and named it Mj Cdc42. Mj Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of Mj Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that Mj Cdc42 interacted with an arginine kinase ( Mj AK). By analyzing the binding activity and enzyme activity of Mj AK and its mutant, Δ Mj AK, we found that Mj AK could enhance the replication of WSSV in shrimp. Mj AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of Mj AK in WSSV replication. Further study demonstrated that the binding of Mj Cdc42 and Mj AK depends on Cys 271 of Mj AK and suppresses the WSSV replication-promoting effect of Mj AK. By interacting with the active site of Mj AK and suppressing its enzyme activity, Mj Cdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. Copyright © 2017 American Society for Microbiology.

A New Genetically Encoded Single-Chain Biosensor for Cdc42 Based on FRET, Useful for Live-Cell Imaging

Science.gov (United States)

Cox, Dianne; Hodgson, Louis

2014-01-01

Cdc42 is critical in a myriad of cellular morphogenic processes, requiring precisely regulated activation dynamics to affect specific cellular events. To facilitate direct observations of Cdc42 activation in live cells, we developed and validated a new biosensor of Cdc42 activation. The biosensor is genetically encoded, of single-chain design and capable of correctly localizing to membrane compartments as well as interacting with its upstream regulators including the guanine nucleotide dissociation inhibitor. We characterized this new biosensor in motile mouse embryonic fibroblasts and observed robust activation dynamics at leading edge protrusions, similar to those previously observed for endogenous Cdc42 using the organic dye-based biosensor system. We then extended our validations and observations of Cdc42 activity to macrophages, and show that this new biosensor is able to detect differential activation patterns during phagocytosis and cytokine stimulation. Furthermore, we observe for the first time, a highly transient and localized activation of Cdc42 during podosome formation in macrophages, which was previously hypothesized but never directly visualized. PMID:24798463

Conserved CDC20 cell cycle functions are carried out by two of the five isoforms in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Zoltán Kevei

Full Text Available The CDC20 and Cdh1/CCS52 proteins are substrate determinants and activators of the Anaphase Promoting Complex/Cyclosome (APC/C E3 ubiquitin ligase and as such they control the mitotic cell cycle by targeting the degradation of various cell cycle regulators. In yeasts and animals the main CDC20 function is the destruction of securin and mitotic cyclins. Plants have multiple CDC20 gene copies whose functions have not been explored yet. In Arabidopsis thaliana there are five CDC20 isoforms and here we aimed at defining their contribution to cell cycle regulation, substrate selectivity and plant development.Studying the gene structure and phylogeny of plant CDC20s, the expression of the five AtCDC20 gene copies and their interactions with the APC/C subunit APC10, the CCS52 proteins, components of the mitotic checkpoint complex (MCC and mitotic cyclin substrates, conserved CDC20 functions could be assigned for AtCDC20.1 and AtCDC20.2. The other three intron-less genes were silent and specific for Arabidopsis. We show that AtCDC20.1 and AtCDC20.2 are components of the MCC and interact with mitotic cyclins with unexpected specificity. AtCDC20.1 and AtCDC20.2 are expressed in meristems, organ primordia and AtCDC20.1 also in pollen grains and developing seeds. Knocking down both genes simultaneously by RNAi resulted in severe delay in plant development and male sterility. In these lines, the meristem size was reduced while the cell size and ploidy levels were unaffected indicating that the lower cell number and likely slowdown of the cell cycle are the cause of reduced plant growth.The intron-containing CDC20 gene copies provide conserved and redundant functions for cell cycle progression in plants and are required for meristem maintenance, plant growth and male gametophyte formation. The Arabidopsis-specific intron-less genes are possibly "retrogenes" and have hitherto undefined functions or are pseudogenes.

Phosphatidylserine and GTPase activation control Cdc42 nanoclustering to counter dissipative diffusion.

Science.gov (United States)

Sartorel, Elodie; Ünlü, Caner; Jose, Mini; Massoni-Laporte, Aurélie; Meca, Julien; Sibarita, Jean-Baptiste; McCusker, Derek

2018-04-18

The anisotropic organization of plasma membrane constituents is indicative of mechanisms that drive the membrane away from equilibrium. However, defining these mechanisms is challenging due to the short spatio-temporal scales at which diffusion operates. Here, we use high-density single protein tracking combined with photoactivation localization microscopy (sptPALM) to monitor Cdc42 in budding yeast, a system in which Cdc42 exhibits anisotropic organization. Cdc42 exhibited reduced mobility at the cell pole, where it was organized in nanoclusters. The Cdc42 nanoclusters were larger at the cell pole than those observed elsewhere in the cell. These features were exacerbated in cells expressing Cdc42-GTP, and were dependent on the scaffold Bem1, which contributed to the range of mobility and nanocluster size exhibited by Cdc42. The lipid environment, in particular phosphatidylserine levels, also played a role in regulating Cdc42 nanoclustering. These studies reveal how the mobility of a Rho GTPase is controlled to counter the depletive effects of diffusion, thus stabilizing Cdc42 on the plasma membrane and sustaining cell polarity. Movie S1 Movie S1 sptPALM imaging of live yeast expressing Pil1-mEOS expressed at the genomic locus. Pil1-mEOS was simultaneously photo-converted with a 405 nm laser and imaged with a 561 nm laser using HiLo illumination. Images were acquired at 20 ms intervals, of which 300 frames are shown at 7 frames per second.

Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal

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Pfeifer Aleksandra

2009-06-01

Full Text Available Abstract Background The molecular mechanisms of cell cycle exit are poorly understood. Studies on lymphocytes at cell cycle exit after growth factor deprivation have predominantly focused on the initiation of apoptosis. We aimed to study gene expression profile of primary and immortalised IL-2-dependent human T cells forced to exit the cell cycle by growth factor withdrawal, before apoptosis could be evidenced. Results By the Affymetrix microarrays HG-U133 2.0 Plus, 53 genes were distinguished as differentially expressed before and soon after IL-2 deprivation. Among those, PIM1, BCL2, IL-8, HBEGF, DUSP6, OSM, CISH, SOCS2, SOCS3, LIF and IL13 were down-regulated and RPS24, SQSTM1, TMEM1, LRRC8D, ECOP, YY1AP1, C1orf63, ASAH1, SLC25A46 and MIA3 were up-regulated. Genes linked to transcription, cell cycle, cell growth, proliferation and differentiation, cell adhesion, and immune functions were found to be overrepresented within the set of the differentially expressed genes. Conclusion Cell cycle exit of the growth factor-deprived T lymphocytes is characterised by a signature of differentially expressed genes. A coordinate repression of a set of genes known to be induced during T cell activation is observed. However, growth arrest following exit from the cell cycle is actively controlled by several up-regulated genes that enforce the non-dividing state. The identification of genes involved in cell cycle exit and quiescence provides new hints for further studies on the molecular mechanisms regulating the non-dividing state of a cell, the mechanisms closely related to cancer development and to many biological processes.

PUBG; purex solvent extraction process model. [IBM3033; CDC CYBER175; FORTRAN IV

Energy Technology Data Exchange (ETDEWEB)

Geldard, J.F.; Beyerlein, A.L.

PUBG is a chemical model of the Purex solvent extraction system, by which plutonium and uranium are recovered from spent nuclear fuel rods. The system comprises a number of mixer-settler banks. This discrete stage structure is the basis of the algorithms used in PUBG. The stages are connected to provide for countercurrent flow of the aqueous and organic phases. PUBG uses the common convention that has the aqueous phase enter at the lowest numbered stage and exit at the highest one; the organic phase flows oppositely. The volumes of the mixers are smaller than those of the settlers. The mixers generate a fine dispersion of one phase in the other. The high interfacial area is intended to provide for rapid mass transfer of the plutonium and uranium from one phase to the other. The separation of this dispersion back into the two phases occurs in the settlers. The species considered by PUBG are Hydrogen (1+), Plutonium (4+), Uranyl Oxide (2+), Plutonium (3+), Nitrate Anion, and reductant in the aqueous phase and Hydrogen (1+), Uranyl Oxide (2+), Plutonium (4+), and TBP (tri-n-butylphosphate) in the organic phase. The reductant used in the Purex process is either Uranium (4+) or HAN (hydroxylamine nitrate).IBM3033;CDC CYBER175; FORTRAN IV; OS/MVS or OS/MVT (IBM3033), NOS 1.3 (CDC CYBER175); The IBM3033 version requires 150K bytes of memory for execution; 62,000 (octal) words are required by the CDC CYBER175 version..

Parkin Regulates Mitosis and Genomic Stability through Cdc20/Cdh1

NARCIS (Netherlands)

Lee, S.B.; Kim, J.J.; Nam, H.J.; Gao, B.; Yin, P.; Qin, B.; Yi, S.Y.; Ham, H.; Evans, D.; Kim, S.H.; Zhang, J.; Deng, M.; Liu, T.; Zhang, H.; Billadeau, D.D.; Wang, L.; Giaime, E.; Shen, J.; Pang, Y.P.; Jen, J.; Deursen, J.M.A. van; Lou, Z.

2015-01-01

Mutations in the E3 ubiquitin ligase Parkin have been linked to familial Parkinson's disease. Parkin has also been implicated in mitosis through mechanisms that are unclear. Here we show that Parkin interacts with anaphase promoting complex/cyclosome (APC/C) coactivators Cdc20 and Cdh1 to mediate

Archaeal orthologs of Cdc45 and GINS form a stable complex that stimulates the helicase activity of MCM.

Science.gov (United States)

Xu, Yuli; Gristwood, Tamzin; Hodgson, Ben; Trinidad, Jonathan C; Albers, Sonja-Verena; Bell, Stephen D

2016-11-22

The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome.

CDC Disease Detective Camp

Centers for Disease Control (CDC) Podcasts

2010-08-02

The CDC Disease Detective Camp gives rising high school juniors and seniors exposure to key aspects of the CDC, including basic epidemiology, infectious and chronic disease tracking, public health law, and outbreak investigations. The camp also helps students explore careers in public health.  Created: 8/2/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/2/2010.

The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse

DEFF Research Database (Denmark)

Vasyutina, Elena; Martarelli, Benedetta; Brakebusch, Cord

2009-01-01

Rac1 and Cdc42 are small G-proteins that regulate actin dynamics and affect plasma membrane protrusion and vesicle traffic. We used conditional mutagenesis in mice to demonstrate that Rac1 and Cdc42 are essential for myoblast fusion in vivo and in vitro. The deficit in fusion of Rac1 or Cdc42 mut...... genetic analysis demonstrates thus that the function of Rac in myoblast fusion is evolutionarily conserved from insects to mammals and that Cdc42, a molecule hitherto not implicated in myoblast fusion, is essential for the fusion of murine myoblasts....

Exit prostitution

DEFF Research Database (Denmark)

Mehlsen, Line; Aslaug Kjær, Agnete; Amilon, Anna

2016-01-01

Dette statusnotat for projektet ”Exit Prostitution” belyser de foreløbige resultater og tendenser for projektet. Exit Prostitution løb oprindeligt fra april 2012 til udgangen af 2015, men med en nylig forlængelse løber projektet til udgangen af 2016. Projektet befinder sig således i slutningen af...... afprøvet med succes i forhold til hjemløshed både nationalt og internationalt. Målet med anvendelsen af metoden i forhold til målgruppen for Exit Prostitution er, at borgere med prostitutionserfaring, som ønsker at ophøre med salg af seksuelle ydelser eller ønsker at opleve en forbedring af deres...

A novel functional polymorphism in the Cdc6 promoter is associated with the risk for hepatocellular carcinoma

International Nuclear Information System (INIS)

Xiong Xingdong; Fang Jianhong; Qiu Fuen; Zhao Jing; Cheng Jiasen; Yuan Yunfei; Li Shengping; Zhuang Shimei

2008-01-01

Cdc6 is essential for DNA replication and its deregulation is involved in carcinogenesis. To date, the biological significance of the polymorphism in Cdc6 promoter is still unknown. In this study, we aimed to evaluate the influence of the Cdc6 -515A>G polymorphism (rs4134994) on the individual's susceptibility to cancer and on the function of Cdc6. The Cdc6 -515A>G polymorphism was genotyped in 387 hepatocellular carcinoma (HCC) and 389 age- and sex-matched healthy subjects. The association between the genotypes and the risk for HCC was then estimated by unconditional logistic regression analysis with adjustment for age, sex and HBV status. Compared with the AA homozygotes, the homozygous GG genotype (adjusted OR = 0.36, 95% confidence interval (CI) = 0.18-0.72, P = 0.004) or the combined AG/GG genotypes (adjusted OR = 0.56, 95% CI = 0.36-0.86, P = 0.008) were statistically significantly associated with the reduced risk for HCC. Moreover, the analysis using luciferase reporter system showed that the G-allelic Cdc6 promoter displayed a decreased transcriptional activity compared with the A-allelic one. These results indicate that the individuals with G allele may have reduced Cdc6 expression and are therefore in reduced risk for HCC. Further investigation using electrophoretic mobility shift assay (EMSA) revealed that the G allele had a stronger binding strength to nuclear protein(s) which might function as negative regulator(s) for Cdc6 transcription. Our findings suggest that the -515A>G polymorphism may affect the Cdc6 promoter binding affinity with nuclear protein(s) and in turn the Cdc6 expression, which consequently modulates the individual's susceptibility to HCC

Binding of Cdc42 to phospholipase D1 is important in neurite outgrowth of neural stem cells

International Nuclear Information System (INIS)

Yoon, Mee-Sup; Cho, Chan Ho; Lee, Ki Sung; Han, Joong-Soo

2006-01-01

We previously demonstrated that phospholipase D (PLD) expression and PLD activity are upregulated during neuronal differentiation. In the present study, employing neural stem cells from the brain cortex of E14 rat embryos, we investigated the role of Rho family GTPases in PLD activation and in neurite outgrowth of neural stem cells during differentiation. As neuronal differentiation progressed, the expression levels of Cdc42 and RhoA increased. Furthermore, Cdc42 and PLD1 were mainly localized in neurite, whereas RhoA was localized in cytosol. Co-immunoprecipitation revealed that Cdc42 was bound to PLD1 during differentiation, whereas RhoA was associated with PLD1 during both proliferation and differentiation. These results indicate that the association between Cdc42 and PLD1 is related to neuronal differentiation. To examine the effect of Cdc42 on PLD activation and neurite outgrowth, we transfected dominant negative Cdc42 (Cdc42N17) and constitutively active Cdc42 (Cdc42V12) into neural stem cells, respectively. Overexpression of Cdc42N17 decreased both PLD activity and neurite outgrowth, whereas co-transfection with Cdc42N17 and PLD1 restored them. On the other hand, Cdc42V12 increased both PLD activity and neurite outgrowth, suggesting that active state of Cdc42 is important in upregulation of PLD activity which is responsible for the increase of neurite outgrowth

Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation.

Science.gov (United States)

Ikehata, Mikiko; Yamada, Atsushi; Fujita, Koji; Yoshida, Yuko; Kato, Tadashi; Sakashita, Akiko; Ogata, Hiroaki; Iijima, Takehiko; Kuroda, Masahiko; Chikazu, Daichi; Kamijo, Ryutaro

2018-04-20

Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1 fl/fl ; Cdc42 fl/fl ; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42 fl/fl ; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1 fl/fl ; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development. Copyright © 2018 Elsevier Inc. All rights reserved.

Cdc25A promotes cell survival by stimulating NF-κB activity through IκB-α phosphorylation and destabilization

International Nuclear Information System (INIS)

Hong, Hey-Young; Choi, Jiyeon; Cho, Young-Wook; Kim, Byung-Chul

2012-01-01

Highlights: ► We examine the antiapoptotic mechanisms of Cdc25A. ► Smad7 decreases the phosphorylation of IκB-alpha at Ser-32. ► Smad7 positively regulates NF-κB activity through IκB-alpha ubiquitination. -- Abstract: Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-κB) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (Iκ-Bα) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-κB. Inhibition of NF-κB activity by chemical inhibitor or overexpression of Iκ-Bα in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-κB activity regulation and it may be an important survival mechanism of cancer cells.

Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

International Nuclear Information System (INIS)

Jiang, Jiahua; Jedinak, Andrej; Sliva, Daniel

2011-01-01

Highlights: ► Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. ► CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. ► GDNT inhibits expression of CDC20 in breast cancer cells. ► GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. ► GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes—ganoderic and lucidenic acids—the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

Energy Technology Data Exchange (ETDEWEB)

Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

Chlamydia - CDC Fact Sheet

Science.gov (United States)

... Archive STDs Home Page Bacterial Vaginosis (BV) Chlamydia Gonorrhea Genital Herpes Hepatitis HIV/AIDS & STDs Human Papillomavirus ( ... sheet Pelvic Inflammatory Disease (PID) – CDC fact sheet Gonorrhea – CDC fact sheet STDs Home Page Bacterial Vaginosis ( ...

Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

Science.gov (United States)

Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

2016-10-01

Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form

The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas

OpenAIRE

Wang, Zhihui; Tropè, Claes G; Suo, Zhenhe; Trøen, Gunhild; Yang, Guanrui; Nesland, Jahn M; Holm, Ruth

2008-01-01

Background 14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown. Methods ...

CDC Disease Detective Camp

Centers for Disease Control (CDC) Podcasts

The CDC Disease Detective Camp gives rising high school juniors and seniors exposure to key aspects of the CDC, including basic epidemiology, infectious and chronic disease tracking, public health law, and outbreak investigations. The camp also helps students explore careers in public health.

Sequencing Analysis of Mutant Allele $cdc$28-$srm$ of Protein Kinase CDC28 and Molecular Dynamics Study of Glycine-Rich Loop in Wild-Type and Mutant Allele G16S of CDK2 as Model

CERN Document Server

Koltovaya, N A; Kholmurodov, Kh T; Kretov, D A

2005-01-01

The central role that cyclin-dependent kinases play in the timing of cell division and the high incidence of genetic alteration of CDKs or deregulation of CDK inhibitors in a number of cancers make CDC28 of the yeast \\textit{Saccharomyces cerevisiae }very attractive model for studies of mechanisms of CDK regulation. Earlier it was found that certain gene mutations including \\textit{cdc28-srm} affect cell cycle progression, maintenance of different genetic structures and increase cell sensitivity to ionizing radiation. A~\\textit{cdc28-srm} mutation is not temperature-sensitive mutation and differs from the known \\textit{cdc28-ts }mutations because it has the evident phenotypic manifestations at 30 $^{\\circ}$C. Sequencing analysis of \\textit{cdc28-srm} revealed a single nucleotide substitution G20S. This is a third glycine in a conserved sequence GxGxxG in the G-rich loop positioned opposite the activation T-loop. Despite its demonstrated importance, the role of the G-loop has remained unclear. The crystal stru...

Cdc42 controls primary mesenchyme cell morphogenesis in the sea urchin embryo.

Science.gov (United States)

Sepúlveda-Ramírez, Silvia P; Toledo-Jacobo, Leslie; Henson, John H; Shuster, Charles B

2018-05-15

In the sea urchin embryo, gastrulation is characterized by the ingression and directed cell migration of primary mesenchyme cells (PMCs), as well as the primary invagination and convergent extension of the endomesoderm. Like all cell shape changes, individual and collective cell motility is orchestrated by Rho family GTPases and their modulation of the actomyosin cytoskeleton. And while endomesoderm specification has been intensively studied in echinoids, much less is known about the proximate regulators driving cell motility. Toward these ends, we employed anti-sense morpholinos, mutant alleles and pharmacological inhibitors to assess the role of Cdc42 during sea urchin gastrulation. While inhibition of Cdc42 expression or activity had only mild effects on PMC ingression, PMC migration, alignment and skeletogenesis were disrupted in the absence of Cdc42, as well as elongation of the archenteron. PMC migration and patterning of the larval skeleton relies on the extension of filopodia, and Cdc42 was required for filopodia in vivo as well as in cultured PMCs. Lastly, filopodial extension required both Arp2/3 and formin actin-nucleating factors, supporting models of filopodial nucleation observed in other systems. Together, these results suggest that Cdc42 plays essential roles during PMC cell motility and organogenesis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Drug design with Cdc7 kinase: a potential novel cancer therapy target

Directory of Open Access Journals (Sweden)

Masaaki Sawa

2008-11-01

Full Text Available Masaaki Sawa1, Hisao Masai21Carna Biosciences, Inc., Kobe, Japan; 2Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAbstract: Identification of novel molecular targets is critical in development of new and efficient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not significantly affect viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC50 of less than 10 nM have been identified, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.Keywords: Cdc7 kinase, cell cycle, replication fork, genome stability, DNA damages, ATP-binding pocket, kinase inhibitor

Hedgehog signaling acts with the temporal cascade to promote neuroblast cell cycle exit.

Directory of Open Access Journals (Sweden)

Phing Chian Chai

Full Text Available In Drosophila postembryonic neuroblasts, transition in gene expression programs of a cascade of transcription factors (also known as the temporal series acts together with the asymmetric division machinery to generate diverse neurons with distinct identities and regulate the end of neuroblast proliferation. However, the underlying mechanism of how this "temporal series" acts during development remains unclear. Here, we show that Hh signaling in the postembryonic brain is temporally regulated; excess (earlier onset of Hh signaling causes premature neuroblast cell cycle exit and under-proliferation, whereas loss of Hh signaling causes delayed cell cycle exit and excess proliferation. Moreover, the Hh pathway functions downstream of Castor but upstream of Grainyhead, two components of the temporal series, to schedule neuroblast cell cycle exit. Interestingly, hh is likely a target of Castor. Hence, Hh signaling provides a link between the temporal series and the asymmetric division machinery in scheduling the end of neurogenesis.

Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

Science.gov (United States)

Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

2017-11-01

In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Histopathological detection of entry and exit holes in human skin wounds caused by firearms.

Science.gov (United States)

Baptista, Marcus Vinícius; d'Ávila, Solange C G P; d'Ávila, Antônio Miguel M P

2014-07-01

The judiciary needs forensic medicine to determine the difference between an entry hole and an exit hole in human skin caused by firearms for civilian use. This important information would be most useful if a practical and accurate method could be done with low-cost and minimal technological resources. Both macroscopic and microscopic analyses were performed on skin lesions caused by firearm projectiles, to establish histological features of 14 entry holes and 14 exit holes. Microscopically, in the abrasion area macroscopically observed, there were signs of burns (sub-epidermal cracks and keratinocyte necrosis) in the entrance holes in all cases. These signs were not found in three exit holes which showed an abrasion collar, nor in other exit holes. Some other microscopic features not found in every case were limited either to entry holes, such as cotton fibres, grease deposits, or tattooing in the dermis, or to exit holes, such as adipose tissue, bone or muscle tissue in the dermis. Coagulative necrosis of keratinocytes and sub-epidermal cracks are characteristic of entry holes. Despite the small sample size, it can be safely inferred that this is an important microscopic finding, among others less consistently found, to define an entry hole in questionable cases. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Cdc25A promotes cell survival by stimulating NF-{kappa}B activity through I{kappa}B-{alpha} phosphorylation and destabilization

Energy Technology Data Exchange (ETDEWEB)

Hong, Hey-Young; Choi, Jiyeon [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of); Cho, Young-Wook [Korea Basic Science Institute, Chuncheon Center, Gangwondaehak-gil 1, Chuncheon 200-701 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of)

2012-04-06

Highlights: Black-Right-Pointing-Pointer We examine the antiapoptotic mechanisms of Cdc25A. Black-Right-Pointing-Pointer Smad7 decreases the phosphorylation of I{kappa}B-alpha at Ser-32. Black-Right-Pointing-Pointer Smad7 positively regulates NF-{kappa}B activity through I{kappa}B-alpha ubiquitination. -- Abstract: Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-{kappa}B) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (I{kappa}-B{alpha}) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-{kappa}B. Inhibition of NF-{kappa}B activity by chemical inhibitor or overexpression of I{kappa}-B{alpha} in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-{kappa}B activity regulation and it may be an important survival mechanism of cancer cells.

Exit Polls and Voter Turnout

DEFF Research Database (Denmark)

Andersen, Asger Lau; Jensen, Thomas

2014-01-01

After the 2009 referendum on a proposed change to the Danish Law of Succession, it was widely claimed that the early publication of exit poll results changed the rate of turnout and eventually the outcome. We investigate this claim and contribute to the wider debate on the implications of exit...... polls by setting up and analyzing a formal model. We find that the introduction of an exit poll influences the incentive to vote both before and after the poll is published, but the signs of the effects are generally ambiguous. The observation that exit polls influence the incentive to vote even before...

MiR-27a Promotes Hemin-Induced Erythroid Differentiation of K562 Cells by Targeting CDC25B

Directory of Open Access Journals (Sweden)

Dongsheng Wang

2018-03-01

Full Text Available Background/Aims: MicroRNAs (miRNAs play a crucial role in erythropoiesis. MiR-23a∼27a∼24-2 clusters have been proven to take part in erythropoiesis via some proteins. CDC25B (cell division control Cdc2 phosphostase B is also the target of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown. Methods: To evaluate the potential role of miR-27a during erythroid differentiation, we performed miR-27a gain- and loss-of-function experiments on hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation at different time points. At the same time, the γ-globin gene also was measured via real-time PCR. According to the results of the chips, we screened the target protein of miR-27a through a dual-luciferase reporter assay and identified it via Western blot analyses. To evaluate the function of CDC25B, benzidine staining and flow cytometry were employed to detect the cell differentiation and cell cycle. Results: We found that miR-27a promotes hemin-induced erythroid differentiation of human K562 cells by targeting cell division cycle 25 B (CDC25B. Overexpression of miR-27a promotes the differentiation of hemin-induced K562 cells, as demonstrated by γ-globin overexpression. The inhibition of miR-27a expression suppresses erythroid differentiation, thus leading to a reduction in the γ-globin gene. CDC25B was identified as a new target of miR-27a during erythroid differentiation. Overexpression of miR-27a led to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B affected erythroid differentiation, as assessed by γ-globin expression. Conclusion: This study is the first report of the interaction between miR-27a and CDC25B, and it improves the understanding of miRNA functions during erythroid differentiation.

CDC Climat - 2011 Sustainable Development Report

International Nuclear Information System (INIS)

2012-08-01

CDC Climat is the Caisse des Depots (CDC) subsidiary that is dedicated to combating climate change. Its activities aim to support the transition towards a low resource and low greenhouse gas emission (GHG) economy, through services that are cutting-edge, pro table, and in line with CDC's public policy goals. Through its corporate purpose, CDC Climat embodies the CDC's commitments in the sustainable development field. CDC Climat supports the implementation of public GHG emission reduction policies, primarily through emission trading schemes at the European and international level. Since it was founded in 2010, and throughout 2011, its strategic priorities have consisted in: - developing a long-term policy for investing in carbon credits generated by environmental initiatives, as part of the project mechanisms set up by the Kyoto Protocol, and used in the European Emission Trading Scheme; - supporting the development of its investments in carbon finance operators, like BlueNext, the European carbon exchange, for instance; - broadening the scope of its research into climate economics, which is supported by CDC and available to everyone, in order to serve the public and private players concerned. Its teams have supported French and European governments, international organisations and the United Nations, and various NGOs in their work and thinking on the future of tools for combating climate change. They have specifically contributed reports based on their research and operational feedback. When it was founded, CDC Climat was closely linked to public policies aimed at combating climate change via allowance and carbon trading mechanisms. The difficulties encountered by international negotiations, together with the effects of the economic and financial downturn in Europe, have resulted in a very pronounced fall in the price of carbon assets on these markets since the summer of 2011, with no prospect of recovery for several years. This environment is calling some of the

Firm Exit, Technological Progress and Trade

DEFF Research Database (Denmark)

Schröder, Philipp; Sørensen, Allan

The dynamics of export market exit and firm closure have found limited attention in the new heterogeneous-firms trade literature. In fact, several of the predictions on firm survival and exit stemming from this new class of models are at odds with the stylized facts. Empirically, higher productiv......The dynamics of export market exit and firm closure have found limited attention in the new heterogeneous-firms trade literature. In fact, several of the predictions on firm survival and exit stemming from this new class of models are at odds with the stylized facts. Empirically, higher...... productivity firms survive longer, most firm closures are young firms, higher productivity exporters are more likely to continue to export compared to less productive exporters and market exits as well as firm closures are typically preceded by periods of contracting market shares. The present paper shows...... liberalization on export market exit and firm closure....

13 CFR 120.851 - CDC ethical requirements.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their Associates must act ethically and exhibit good character. They must meet all of the ethical requirements of...

Promoting Exit from Violent Extremism

DEFF Research Database (Denmark)

Dalgaard-Nielsen, Anja

2013-01-01

A number of Western countries are currently adding exit programs targeting militant Islamists to their counterterrorism efforts. Drawing on research into voluntary exit from violent extremism, this article identifies themes and issues that seem to cause doubt, leading to exit. It then provides a ...... the influence attempt as subtle as possible, use narratives and self-affirmatory strategies to reduce resistance to persuasion, and consider the possibility to promote attitudinal change via behavioral change as an alternative to seek to influence beliefs directly....

Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of sterol regulatory element-binding protein in fission yeast.

Science.gov (United States)

Burr, Risa; Ribbens, Diedre; Raychaudhuri, Sumana; Stewart, Emerson V; Ho, Jason; Espenshade, Peter J

2017-09-29

Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA + ) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe , generating a list of many previously unknown potential Cdc48-binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes, Cdc48-Ufd1 and Cdc48-Rbd2, are required for SREBP activation and low-oxygen adaptation in S. pombe . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Ufd1-Npl4 Recruit Cdc48 for Disassembly of Ubiquitylated CMG Helicase at the End of Chromosome Replication

Directory of Open Access Journals (Sweden)

Marija Maric

2017-03-01

Full Text Available Disassembly of the Cdc45-MCM-GINS (CMG DNA helicase is the key regulated step during DNA replication termination in eukaryotes, involving ubiquitylation of the Mcm7 helicase subunit, leading to a disassembly process that requires the Cdc48 “segregase”. Here, we employ a screen to identify partners of budding yeast Cdc48 that are important for disassembly of ubiquitylated CMG helicase at the end of chromosome replication. We demonstrate that the ubiquitin-binding Ufd1-Npl4 complex recruits Cdc48 to ubiquitylated CMG. Ubiquitylation of CMG in yeast cell extracts is dependent upon lysine 29 of Mcm7, which is the only detectable site of ubiquitylation both in vitro and in vivo (though in vivo other sites can be modified when K29 is mutated. Mutation of K29 abrogates in vitro recruitment of Ufd1-Npl4-Cdc48 to the CMG helicase, supporting a model whereby Ufd1-Npl4 recruits Cdc48 to ubiquitylated CMG at the end of chromosome replication, thereby driving the disassembly reaction.

FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42

DEFF Research Database (Denmark)

Kage, Frieda; Steffen, Anika; Ellinger, Adolf

2017-01-01

The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly fa...

CDC 7600 Module

CERN Multimedia

1970-01-01

The CDC 7600 has been created by Seymour Cray. It was designed to be compatible with the 6600, which allows for a substantial increase in performance. Furthermore the rise of new technologies has enabled this performance by reducing the minor cycle clock period from 100 ns to 27.5 ns (4 time faster). A very large machine, the 7600 had over 120 miles of hand-wired interconnections. It was the most powerful computer of its time. However, this speed caused a ground-loop problem causing intermittent faults, and eventually requiring all modules to be fitted with sheathed rubber bands. The CDC 7600 was replaced in 1983 by CRAY-1A.

Inhibition of Cdc42 and Rac1 activities in pheochromocytoma, the adrenal medulla tumor.

Science.gov (United States)

Croisé, Pauline; Brunaud, Laurent; Tóth, Petra; Gasman, Stéphane; Ory, Stéphane

2017-04-03

Altered Rho GTPase signaling has been linked to many types of cancer. As many small G proteins, Rho GTPases cycle between an active and inactive state thanks to specific regulators that catalyze exchange of GDP into GTP (Rho-GEF) or hydrolysis of GTP into GDP (Rho-GAP). Recent studies have shown that alteration takes place either at the level of Rho proteins themselves (expression levels, point mutations) or at the level of their regulators, mostly RhoGEFs and RhoGAPs. Most reports describe Rho GTPases gain of function that may participate to the tumorigenesis processes. In contrast, we have recently reported that decreased activities of Cdc42 and Rac1 as well as decreased expression of 2 Rho-GEFs, FARP1 and ARHGEF1, correlate with pheochromocytomas, a tumor developing in the medulla of the adrenal gland (Croisé et al., Endocrine Related Cancer, 2016). Here we highlight the major evidence and further study the correlation between Rho GTPases activities and expression levels of ARHGEF1 and FARP1. Finally we also discuss how the decrease of Cdc42 and Rac1 activities may help human pheochromocytomas to develop and comment the possible relationship between FARP1, ARHGEF1 and the 2 Rho GTPases Cdc42 and Rac1 in tumorigenesis.

CDC25A Protein Stability Represents a Previously Unrecognized Target of HER2 Signaling in Human Breast Cancer: Implication for a Potential Clinical Relevance in Trastuzumab Treatment

Directory of Open Access Journals (Sweden)

Emanuela Brunetto

2013-06-01

Full Text Available The CDC25A-CDK2 pathway has been proposed as critical for the oncogenic action of human epidermal growth factor receptor 2 (HER2 in mammary epithelial cells. In particular, transgenic expression of CDC25A cooperates with HER2 in promoting mammary tumors, whereas CDC25A hemizygous loss attenuates the HER2-induced tumorigenesis penetrance. On the basis of this evidence of a synergism between HER2 and the cell cycle regulator CDC25A in a mouse model of mammary tumorigenesis, we investigated the role of CDC25A in human HER2-positive breast cancer and its possible implications in therapeutic response. HER2 status and CDC25A expression were assessed in 313 breast cancer patients and we found statistically significant correlation between HER2 and CDC25A (P = .007. Moreover, an HER2-positive breast cancer subgroup with high levels of CDC25A and very aggressive phenotype was identified (P = .005. Importantly, our in vitro studies on breast cancer cell lines showed that the HER2 inhibitor efficacy on cell growth and viability relied also on CDC25A expression and that such inhibition induces CDC25A down-regulation through phosphatidylinositol 3-kinase/protein kinase B pathway and DNA damage response activation. In line with this observation, we found a statistical significant association between CDC25A overexpression and trastuzumab-combined therapy response rate in two different HER2-positive cohorts of trastuzumab-treated patients in either metastatic or neoadjuvant setting (P = .018 for the metastatic cohort and P = .021 for the neoadjuvant cohort. Our findings highlight a link between HER2 and CDC25A that positively modulates HER2- targeted therapy response, suggesting that, in HER2-positive breast cancer patients, CDC25A overexpression affects trastuzumab sensitivity.

Regulation of Cellular and Molecular Functions by Protein ...

Indian Academy of Sciences (India)

... a high-energy linkage. The free energy of hydrolysis 1 of protein bound tyrosine phosphate ... protein kinases, cdc2 kinase (which regulates cell division cycle) and related cdc ... residues in response to extracellular signals such as hormones or growth factors. ... involved in regulating glycogen metabolism. The activity of.

Lysine acetylation targets protein complexes and co-regulates major cellular functions

DEFF Research Database (Denmark)

Choudhary, Chuna Ram; Kumar, Chanchal; Gnad, Florian

2009-01-01

Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600......, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other...

The human ubiquitin-conjugating enzyme Cdc34 controls cellular proliferation through regulation of p27Kip1 protein levels

International Nuclear Information System (INIS)

Butz, Nicole; Ruetz, Stephan; Natt, Francois; Hall, Jonathan; Weiler, Jan; Mestan, Juergen; Ducarre, Monique; Grossenbacher, Rita; Hauser, Patrick; Kempf, Dominique; Hofmann, Francesco

2005-01-01

Ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor p27 Kip1 was shown to be required for the activation of key cyclin-dependent kinases, thereby triggering the onset of DNA replication and cell cycle progression. Although the SCF Skp2 ubiquitin ligase has been reported to mediate p27 Kip1 degradation, the nature of the human ubiquitin-conjugating enzyme involved in this process has not yet been determined at the cellular level. Here, we show that antisense oligonucleotides targeting the human ubiquitin-conjugating enzyme Cdc34 downregulate its expression, inhibit the degradation of p27 Kip1 , and prevent cellular proliferation. Elevation of p27 Kip1 protein level is found to be the sole requirement for the inhibition of cellular proliferation induced upon downregulation of Cdc34. Indeed, reducing the expression of p27 Kip1 with a specific antisense oligonucleotide is sufficient to reverse the anti-proliferative phenotype elicited by the Cdc34 antisense. Furthermore, downregulation of Cdc34 is found to specifically increase the abundance of the SCF Skp2 ubiquitin ligase substrate p27 Kip1 , but has no concomitant effect on the level of IkBα and β-catenin, which are known substrates of a closely related SCF ligase

Cdc42 and RhoA reveal different spatio-temporal dynamics upon local stimulation with Semaphorin-3A

Directory of Open Access Journals (Sweden)

Federico eIseppon

2015-08-01

Full Text Available Small RhoGTPases, such as Cdc42 and RhoA, are key players in integrating external cues and intracellular signaling pathways that regulate growth cone (GC motility. Indeed, Cdc42 is involved in actin polymerization and filopodia formation, whereas RhoA induces GC collapse and neurite retraction through actomyosin contraction. In this study we employed Förster Resonance Energy Transfer (FRET microscopy to study the spatio-temporal dynamics of Cdc42 and RhoA in GCs in response to local Semaphorin-3A stimulation obtained with lipid vesicles filled with Semaphorin-3A and positioned near the selected GC using optical tweezers. We found that Cdc42 and RhoA were activated at the leading edge of NG108-15 neuroblastoma cells during spontaneous cycles of protrusion and retraction, respectively. The release of Semaphorin-3A brought to a progressive activation of RhoA within 30 seconds from the stimulus in the central region of the GC that collapsed and retracted. In contrast, the same stimulation evoked waves of Cdc42 activation propagating away from the stimulated region. A more localized stimulation obtained with Sema3A coated beads placed on the GC, led to Cdc42 active waves that propagated in a retrograde manner with a mean period of 70 seconds, and followed by GC retraction. Therefore, Semaphorin-3A activates both Cdc42 and RhoA with a complex and different spatial-temporal dynamics.

Timely Endocytosis of Cytokinetic Enzymes Prevents Premature Spindle Breakage during Mitotic Exit.

Directory of Open Access Journals (Sweden)

Cheen Fei Chin

2016-07-01

Full Text Available Cytokinesis requires the spatio-temporal coordination of membrane deposition and primary septum (PS formation at the division site to drive acto-myosin ring (AMR constriction. It has been demonstrated that AMR constriction invariably occurs only after the mitotic spindle disassembly. It has also been established that Chitin Synthase II (Chs2p neck localization precedes mitotic spindle disassembly during mitotic exit. As AMR constriction depends upon PS formation, the question arises as to how chitin deposition is regulated so as to prevent premature AMR constriction and mitotic spindle breakage. In this study, we propose that cells regulate the coordination between spindle disassembly and AMR constriction via timely endocytosis of cytokinetic enzymes, Chs2p, Chs3p, and Fks1p. Inhibition of endocytosis leads to over accumulation of cytokinetic enzymes during mitotic exit, which accelerates the constriction of the AMR, and causes spindle breakage that eventually could contribute to monopolar spindle formation in the subsequent round of cell division. Intriguingly, the mitotic spindle breakage observed in endocytosis mutants can be rescued either by deleting or inhibiting the activities of, CHS2, CHS3 and FKS1, which are involved in septum formation. The findings from our study highlight the importance of timely endocytosis of cytokinetic enzymes at the division site in safeguarding mitotic spindle integrity during mitotic exit.

Polo-like kinase-1 is a target of the DNA damage checkpoint

NARCIS (Netherlands)

Smits, V.A.J.; Klompmaker, R.; Arnaud, L.; Rijksen, G.; Nigg, E.A.; Medema, R.H.

2000-01-01

Polo-like kinases (PLKs) have an important role in several stages of mitosis. They contribute to the activation of cyclin B/Cdc2 and are involved in centrosome maturation and bipolar spindle formation at the onset of mitosis1, 2. PLKs also control mitotic exit by regulating the anaphase-promoting

CDC Health Disparities and Inequalities Report--U.S. 2013

Science.gov (United States)

... Women's Health Health Literacy Health Equity CDC Health Disparities & Inequalities Report (CHDIR) Recommend on Facebook Tweet Share ... 2011 Report More Information CDC Releases Second Health Disparities & Inequalities Report - United States, 2013 CDC and its ...

Spoiled Onions: Exposing Malicious Tor Exit Relays

OpenAIRE

Winter, Philipp; Lindskog, Stefan

2014-01-01

Several hundred Tor exit relays together push more than 1 GiB/s of network traffic. However, it is easy for exit relays to snoop and tamper with anonymised network traffic and as all relays are run by independent volunteers, not all of them are innocuous. In this paper, we seek to expose malicious exit relays and document their actions. First, we monitored the Tor network after developing a fast and modular exit relay scanner. We implemented several scanning modules for detecting common attac...

Understanding international exit from a non-economic and emotional perspective: the case of Taiwanese entrepreneurs exit China

OpenAIRE

Lin, Yangpei

2015-01-01

I investigate why Taiwanese entrepreneurs who have invested in China exit. Viewed from the non-economic perspective, there are three main themes in this thesis. Theme A focuses on the non-economic variables in international exit. Theme B examines how incident-generated emotions shape entrepreneur’s actions in internationalization. Theme C presents an overview of the decision-making of international exit, summarizing the finding in Theme A and Theme B and revisiting the theor...

PLK1 regulation of PCNT cleavage ensures fidelity of centriole separation during mitotic exit.

Science.gov (United States)

Kim, Jaeyoun; Lee, Kwanwoo; Rhee, Kunsoo

2015-12-09

Centrioles are duplicated and segregated in close link to the cell cycle. During mitosis, daughter centrioles are disengaged and eventually separated from mother centrioles. New daughter centrioles may be generated only after centriole separation. Therefore, centriole separation is considered a licensing step for centriole duplication. It was previously known that separase specifically cleaves pericentrin (PCNT) during mitotic exit. Here we report that PCNT has to be phosphorylated by PLK1 to be a suitable substrate of separase. Phospho-resistant mutants of PCNT are not cleaved by separase and eventually inhibit centriole separation. Furthermore, phospho-mimetic PCNT mutants rescue centriole separation even in the presence of a PLK1 inhibitor. On the basis on these results, we propose that PLK1 phosphorylation is a priming step for separase-mediated cleavage of PCNT and eventually for centriole separation. PLK1 phosphorylation of PCNT provides an additional layer of regulatory mechanism to ensure the fidelity of centriole separation during mitotic exit.

Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody.

Directory of Open Access Journals (Sweden)

Mark T Winkler

Full Text Available Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH. We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1

Science.gov (United States)

Lee, Min Ho; Cho, Yoonjung; Kim, Do Hyun; Woo, Hyun Jun; Yang, Ji Yeong; Kwon, Hye Jin; Yeon, Min Ji; Park, Min; Kim, Sa-Hyun; Moon, Cheol; Tharmalingam, Nagendran; Kim, Tae Ue; Kim, Jong-Bae

2016-01-01

Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucidate the underlying mechanism, we investigated the cell cycle regulatory molecules involved in the G2/M cell cycle transition. After 24 h of menadione treatment, the protein level of CDK1, CDC25C and cyclin B1 in AGS cells was decreased in a menadione dose-dependent manner. In the time course experiment, the protein level of CDC25C decreased in 6 h, and CDK1and cyclin B1 protein levels began to decrease after 18 h of menadione treatment. We found that mRNA level of CDC25C decreased by menadione treatment in 6 h. Menadione did not have an influence on mRNA level of CDK1 and cyclin B1 though the protein levels were decreased. However, the decreased protein levels of CDK1 and cyclin B1 were recovered by inhibition of proteasome. Collectively, these results suggest that menadione inhibits growth of gastric cancer cells by reducing expression of CDC25C and promoting proteasome mediated degradation of CDK1 and cyclin B1 thereby blocking transition of the cell cycle from G2 phase to M phase. PMID:28077999

Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A

DEFF Research Database (Denmark)

Sørensen, Claus Storgaard; Syljuåsen, Randi G; Falck, Jacob

2003-01-01

Chk1 kinase coordinates cell cycle progression and preserves genome integrity. Here, we show that chemical or genetic ablation of human Chk1 triggered supraphysiological accumulation of the S phase-promoting Cdc25A phosphatase, prevented ionizing radiation (IR)-induced degradation of Cdc25A...

Cdc42 promotes host defenses against fatal infection

DEFF Research Database (Denmark)

Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V

2013-01-01

attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections...... showed that in addition to fibroblasts, the FSP-1 cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this non-specific cre mouse we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate...

CDC WONDER: Births

Data.gov (United States)

U.S. Department of Health & Human Services — The Births (Natality) online databases in CDC WONDER report birth rates, fertility rates and counts of live births occurring within the United States to U.S....

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

Directory of Open Access Journals (Sweden)

Uta Meyer Zum Büschenfelde

2018-05-01

Full Text Available RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1 as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

Science.gov (United States)

Meyer Zum Büschenfelde, Uta; Brandenstein, Laura Isabel; von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg; Kutsche, Kerstin

2018-05-01

RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

Towards A Model of Identity and Role Exit

Directory of Open Access Journals (Sweden)

Jason S. Milne

2011-11-01

Full Text Available Explanations of role exit often focus on how factors associated with a specific role that affect whether the individual will exit a role or not. Other research explains how identities affect our performance in a role. However, no one has yet to demonstrate the connection between role-set factors and identities, and role exit. Using data from a survey of 940 current and former soccer referees, this paper provides a model of role exit that involves a complex of processes that include role-set factors (structural and cultural factors associated with a specific role and identity processes. Specifically, this paper demonstrates that, other than role conflict, identity processes explain the relationship between role-set factors and role exit. The model provides a beginning method for understanding the connection between identities and role exit.

Decreased uv mutagenesis in cdc8, a DNA replication mutant of Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Prakash, L.; Hinkle, D.; Prakash, S.

1978-01-01

A DNA replication mutant of yeast, cdc8, was found to decrease uv-induced reversion of lys2-1, arg4-17, tryl and ural. This effect was observed with all three alleles of cdc8 tested. Survival curves obtained following uv irradiation in cdc8 rad double mutants show that cdc8 is epistatic to rad6, as well as to rad1; cdc8 rad51 double mutants seem to be more sensitive than the single mutants. Since uv-induced reversion in cdc8 rad1 and cdc8 rad51 double mutants is like that of the cdc8 single mutants, we conclude that CDC8 plays a direct role in error-prone repair. To test whether CDC8 codes for a DNA polymerase, we have purified both DNA polymerase I and DNA polymerase II from cdc8 and CDC+ cells. The purified DNA polymerases from cdc8 were no more heat labile than those from CDC+, suggesting that CDC8 is not a structural gene for either enzyme

Educational Inequalities in Exit from Paid Employment among Dutch Workers: The Influence of Health, Lifestyle and Work.

Science.gov (United States)

Robroek, Suzan J W; Rongen, Anne; Arts, Coos H; Otten, Ferdy W H; Burdorf, Alex; Schuring, Merel

2015-01-01

Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle-related factors and work characteristics on educational differences in exit from paid employment. 14,708 Dutch employees participated in a ten-year follow-up study during 1999-2008. At baseline, education, self-perceived health, lifestyle (smoking, alcohol, sports, BMI) and psychosocial (demands, control, rewards) and physical work characteristics were measured by questionnaire. Employment status was ascertained monthly based on tax records. The relation between education, health, lifestyle, work-characteristics and exit from paid employment through disability benefits, unemployment, early retirement and economic inactivity was investigated by competing risks regression analyses. The mediating effects of these factors on educational differences in exit from paid employment were tested using a stepwise approach. Lower educated workers were more likely to exit paid employment through disability benefits (SHR:1.84), unemployment (SHR:1.74), and economic inactivity (SHR:1.53) but not due to early retirement (SHR:0.92). Poor or moderate health, an unhealthy lifestyle, and unfavourable work characteristics were associated with disability benefits and unemployment, and an unhealthy lifestyle with economic inactivity. Educational differences in disability benefits were explained for 40% by health, 31% by lifestyle, and 12% by work characteristics. For economic inactivity and unemployment, up to 14% and 21% of the educational differences could be explained, particularly by lifestyle-related factors. There are educational differences in exit from paid employment, which are partly mediated by health, lifestyle and work

Head-circumference distribution in a large primary care network differs from CDC and WHO curves.

Science.gov (United States)

Daymont, Carrie; Hwang, Wei-Ting; Feudtner, Chris; Rubin, David

2010-10-01

To compare currently available head-circumference growth curves to curves constructed from clinical measurements from patients in a large US primary care network (PCN). We performed a retrospective cohort study of 75 412 patients in an urban-suburban PCN. Patients with a birth weight of curves. The PCN curves were most similar to the National Center for Health Statistics (NCHS) curves and were substantially different from the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) curves. The overall proportion of observations above the 95th percentile was 4.9% (PCN), 6.2% (NCHS), 8.6% (CDC), and 14.0% (WHO). The proportion below the 5th percentile was 4.4% (PCN), 5.1% (NCHS), 2.9% (CDC), and 2.3% (WHO). When using the CDC curves, the proportion above the 95th percentile increased from 0.2% for children younger than 2 weeks to 11.8% for children 12 months old. When using the WHO curves, the proportion above the 95th percentile was >5% at all ages, with a maximum of 18.0% for children older than 24 months. The CDC and WHO head-circumference curves describe different distributions than the clinical measurements in our PCN population, especially for children with larger heads. The resulting percentile misclassification may delay diagnosis in children with intracranial pathology in very young infants and spur unnecessary evaluation of healthy children older than 6 months.

Exit or revival?

International Nuclear Information System (INIS)

Anon.

2001-01-01

The answer given by the international representative at the colloquium:'nuclear: exit or revival? ' was tending towards the revival. The international, democratic, ecological and of energy policy stakes are tackled. (N.C.)

Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence

Energy Technology Data Exchange (ETDEWEB)

Byrne, Ann; McLaren, Rajashree P.; Mason, Paul; Chai, Lilly; Dufault, Michael R.; Huang, Yinyin; Liang, Beirong; Gans, Joseph D.; Zhang, Mindy; Carter, Kara; Gladysheva, Tatiana B.; Teicher, Beverly A.; Biemann, Hans-Peter N.; Booker, Michael; Goldberg, Mark A.; Klinger, Katherine W.; Lillie, James [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Madden, Stephen L., E-mail: steve.madden@genzyme.com [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Jiang, Yide, E-mail: yide.jiang@genzyme.com [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)

2010-01-15

The PSMD14 (POH1, also known as Rpn11/MPR1/S13/CepP1) protein within the 19S complex (19S cap; PA700) is responsible for substrate deubiquitination during proteasomal degradation. The role of PSMD14 in cell proliferation and senescence was explored using siRNA knockdown in carcinoma cell lines. Our results reveal that down-regulation of PSMD14 by siRNA transfection had a considerable impact on cell viability causing cell arrest in the G0-G1 phase, ultimately leading to senescence. The molecular events associated with decreased cell proliferation, cell cycle arrest and senescence include down-regulation of cyclin B1-CDK1-CDC25C, down-regulation of cyclin D1 and up-regulation of p21{sup /Cip} and p27{sup /Kip1}. Most notably, phosphorylation of the retinoblastoma protein was markedly reduced in PSMD14 knockdown cells. A comparative study with PSMB5, a subunit of the 20S proteasome, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events. These data support the view that the 19S and 20S subunits of the proteasome have distinct biological functions and imply that targeting 19S and 20S would have distinct molecular consequences on tumor cells.

The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts.

Science.gov (United States)

Steenblock, Charlotte; Heckel, Tobias; Czupalla, Cornelia; Espírito Santo, Ana Isabel; Niehage, Christian; Sztacho, Martin; Hoflack, Bernard

2014-06-27

The initial step of bone digestion is the adhesion of osteoclasts onto bone surfaces and the assembly of podosomal belts that segregate the bone-facing ruffled membrane from other membrane domains. During bone digestion, membrane components of the ruffled border also need to be recycled after macropinocytosis of digested bone materials. How osteoclast polarity and membrane recycling are coordinated remains unknown. Here, we show that the Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based protein networks. At the plasma membrane, FGD6 couples cell adhesion and actin dynamics by regulating podosome formation through the assembly of complexes comprising the Cdc42-interactor IQGAP1, the Rho GTPase-activating protein ARHGAP10, and the integrin interactors Talin-1/2 or Filamin A. On endosomes and transcytotic vesicles, FGD6 regulates retromer-dependent membrane recycling through its interaction with the actin nucleation-promoting factor WASH. These results provide a mechanism by which a single Cdc42-exchange factor controlling different actin-based processes coordinates cell adhesion, cell polarity, and membrane recycling during bone degradation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Exit from Synchrony in Joint Improvised Motion.

Directory of Open Access Journals (Sweden)

Assi Dahan

Full Text Available Motion synchrony correlates with effective and well-rated human interaction. However, people do not remain locked in synchrony; Instead, they repeatedly enter and exit synchrony. In many important interactions, such as therapy, marriage and parent-infant communication, it is the ability to exit and then re-enter synchrony that is thought to build strong relationship. The phenomenon of entry into zero-phase synchrony is well-studied experimentally and in terms of mathematical modeling. In contrast, exit-from-synchrony is under-studied. Here, we focus on human motion coordination, and examine the exit-from-synchrony phenomenon using experimental data from the mirror game paradigm, in which people perform joint improvised motion, and from human tracking of computer-generated stimuli. We present a mathematical mechanism that captures aspects of exit-from-synchrony in human motion. The mechanism adds a random motion component when the accumulated velocity error between the players is small. We introduce this mechanism to several models for human coordinated motion, including the widely studied HKB model, and the predictor-corrector model of Noy, Dekel and Alon. In all models, the new mechanism produces realistic simulated behavior when compared to experimental data from the mirror game and from tracking of computer generated stimuli, including repeated entry and exit from zero-phase synchrony that generates a complexity of motion similar to that of human players. We hope that these results can inform future research on exit-from-synchrony, to better understand the dynamics of coordinated action of people and to enhance human-computer and human-robot interaction.

Assessment of exit block following pulmonary vein isolation: far-field capture masquerading as entrance without exit block.

Science.gov (United States)

Vijayaraman, Pugazhendhi; Dandamudi, Gopi; Naperkowski, Angela; Oren, Jess; Storm, Randle; Ellenbogen, Kenneth A

2012-10-01

Complete electrical isolation of pulmonary veins (PVs) remains the cornerstone of ablation therapy for atrial fibrillation. Entrance block without exit block has been reported to occur in 40% of the patients. Far-field capture (FFC) can occur during pacing from the superior PVs to assess exit block, and this may appear as persistent conduction from PV to left atrium (LA). To facilitate accurate assessment of exit block. Twenty consecutive patients with symptomatic atrial fibrillation referred for ablation were included in the study. Once PV isolation (entrance block) was confirmed, pacing from all the bipoles on the Lasso catheter was used to assess exit block by using a pacing stimulus of 10 mA at 2 ms. Evidence for PV capture without conduction to LA was necessary to prove exit block. If conduction to LA was noticed, pacing output was decreased until there was PV capture without conduction to LA or no PV capture was noted to assess for far-field capture in both the upper PVs. All 20 patients underwent successful isolation (entrance block) of all 76 (4 left common PV) veins: mean age 58 ± 9 years; paroxysmal atrial fibrillation 40%; hypertension 70%, diabetes mellitus 30%, coronary artery disease 15%; left ventricular ejection fraction 55% ± 10%; LA size 42 ± 11 mm. Despite entrance block, exit block was absent in only 16% of the PVs, suggesting persistent PV to LA conduction. FFC of LA appendage was noted in 38% of the left superior PVs. FFC of the superior vena cava was noted in 30% of the right superior PVs. The mean pacing threshold for FFC was 7 ± 4 mA. Decreasing pacing output until only PV capture (loss of FFC) is noted was essential to confirm true exit block. FFC of LA appendage or superior vena cava can masquerade as persistent PV to LA conduction. A careful assessment for PV capture at decreasing pacing output is essential to exclude FFC. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Tritium in Exit Signs | RadTown USA | US EPA

Science.gov (United States)

2017-08-07

Many exit signs contain tritium to light the sign without batteries or electricity. Using tritium in exit signs allows the sign to remain lit if the power goes out. Tritium is most dangerous when it is inhaled or swallowed. Never tamper with a tritium exit sign. If a tritium exit sign is broken, leave the area immediately and notify the building maintenance staff.

Targeting Hsp90-Cdc37: A Promising Therapeutic Strategy by Inhibiting Hsp90 Chaperone Function.

Science.gov (United States)

Wang, Lei; Li, Li; Gu, Kai; Xu, Xiao-Li; Sun, Yuan; You, Qi-Dong

2017-01-01

The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein- protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Isolation of a cdc28 mutation that abrogates the dependence of S ...

Indian Academy of Sciences (India)

We have isolated a mutation in the budding yeast Saccharomyces cerevisisae CDC28 gene that allows cdc13 cells, carrying damaged DNA, to continue with the cell division cycle. While cdc13 mutant cells are arrested as large-budded cells at the nonpermissive temperature 37°C, the cdc13 cdc28 double mutant culture ...

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

Science.gov (United States)

Bai, Zhiyong; Grant, Barth D.

2015-01-01

Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511

Entry and Exit Dynamics of Nascent Business Owners

DEFF Research Database (Denmark)

Rocha, Vera; Carneiro, Anabela; Varum, Celeste

2015-01-01

results suggest that different exit modes can be predicted by business owners’ entry route. Furthermore, different exit modes exhibit different duration dependence patterns according to the entry mode. Additionally, the paper shows that businesses started after a displacement episode are not necessarily......This paper reports a comprehensive study on the dynamics of nascent business owners using a unique longitudinal matched employer–employee dataset. We follow over 157,000 individuals who leave paid employment and become business owners during the period 1992–2007. The contributions of this paper...... are twofold. First, we analyze both entry and exit, identifying and characterizing different profiles of individuals leaving paid employment to become business owners, and distinguishing exits by dissolution from exits by ownership transfer. Second, we provide new evidence on how particular experiences...

Morphological Analysis of CDC2 and Glycogen Synthase Kinase 3β Phosphorylation as Markers of G2 → M Transition in Glioma

Directory of Open Access Journals (Sweden)

José Javier Otero

2011-01-01

Full Text Available G2 → M transition is a strategic target for glioma chemotherapy. Key players in G2 → M transition include CDC2 and glycogen synthase kinase 3β (GSK3β, which are highly regulated by posttranslational phosphorylation. This report is a morphological analysis of CDC2 and GSK3β phosphorylation using immunohistochemistry in gliomas with different biological properties. GBM showed a 2.8-fold and 5.6-fold increase in number of cells positive for pThr161CDC2 and a 4.2- and 6.9-fold increase in number of cells positive for pTyr15CDC2 relative to oligodendroglioma and ependymoma, respectively. Elevated labeling for inhibited phospho-CDC2 (pTyr15CDC correlates with elevated levels of phosphorylated glycogen synthase kinase 3β (GSK3β. 71% of the GBM cases showed intermediate to high intensity staining for pSer9SGK3β 53% of oligodendroglioma, and 73% of ependymoma showed low intensity staining. CDC2 gene amplification correlates with increased survival in glioblastoma multiforme (GBM and astrocytoma WHO grades II-III, but not in oligodendroglioma WHO grades II-III.

Exploring the Reasons and Ways to Exit: The Entrepreneur Perspective

NARCIS (Netherlands)

Parastuty, Zulaicha; Breitenecker, Robert J.; Schwarz, Erich J.; Harms, Rainer; Bögenhold, Dieter; Bonnet, Jean; Dejardin, Marcus; Garcia Perez de Lema, Domingo

2016-01-01

Research on entrepreneurial exit has received growing attention recently, attributing to the importance of exit in the entrepreneurial process. Yet, the complex phenomena of exit render the research scattered in the field. This research is aimed at understanding entrepreneurial exit at the

The Political Economy of Early Exit

DEFF Research Database (Denmark)

Schmitt, Carina; Starke, Peter

2016-01-01

Large-scale exit from the labour market began in the 1970s in many OECD countries. The literature indicates that individual early retirement decisions are facilitated by generous and accessible ‘pathways’ into retirement in the public pension system, unemployment insurance or disability benefits....... in the tradable sector, against a more traditional class-based logic of welfare state policy-making. Quantitative analysis of employment outcomes in 21 countries shows that the political economy of early exit clearly rests on the sectoral politics of cost-shifting.......Large-scale exit from the labour market began in the 1970s in many OECD countries. The literature indicates that individual early retirement decisions are facilitated by generous and accessible ‘pathways’ into retirement in the public pension system, unemployment insurance or disability benefits....... It is unclear, however, why early exit became so much more prevalent in some countries than in others and why such differences remain, despite a recent shift back towards higher employment rates and ‘active ageing’. We test a logic of sectoral cost-shifting politics involving cross-class alliances...

Association of rheumatic diseases with early exit from paid employment in Portugal.

Science.gov (United States)

Laires, Pedro A; Gouveia, Miguel

2014-04-01

To examine the association between rheumatic diseases (RD) and other chronic morbidity with early exit from paid employment in the Portuguese population. The study population consisted of all people between 50 and 64 years of age (3,762 men and 4,241 women) who participated in the Portuguese National Health Survey, conducted in 2005/2006. Data were collected on demographics, ill-health, lifestyle, and socioeconomic factors. Logistic regression was used to estimate the isolated effect of rheumatic diseases and other chronic diseases on the likelihood of exit from paid employment. At the time of the survey, 45.1 % of the Portuguese population with ages between 50 and 64 years old were not employed. In the nonemployed population, 31.6 % self-reported "poor" to "very poor" health, whereas 16.4 % did so in the employed population. A larger average number of major chronic diseases per capita were also found in those not employed (1.9 vs. 1.4, p paid employment. In particular, rheumatic diseases were more prevalent (43.4 vs. 32.1 %) and associated with early exit from work (OR 1.31; CI 1.12-1.52, p = 0.001). This study suggests an association between RD and other major chronic diseases with early exit from paid employment in Portugal. Thus, health and social protection policies should target these chronic disorders in order to better address sustainability issues and social protection effectiveness.

CDC Kerala 1: Organization of clinical child development services (1987-2013).

Science.gov (United States)

Nair, M K C; George, Babu; Nair, G S Harikumaran; Bhaskaran, Deepa; Leena, M L; Russell, Paul Swamidhas Sudhakar

2014-12-01

The main objective of establishing the Child Development Centre (CDC), Kerala for piloting comprehensive child adolescent development program in India, has been to understand the conceptualization, design and scaling up of a pro-active positive child development initiative, easily replicable all over India. The process of establishing the Child Development Centre (CDC) Kerala for research, clinical services, training and community extension services over the last 25 y, has been as follows; Step 1: Conceptualization--The life cycle approach to child development; Step 2: Research basis--CDC model early stimulation is effective; Step 3: Development and validation of seven simple developmental screening tools; Step 4: CDC Diagnostic services--Ultrasonology and genetic, and metabolic laboratory; Step 5: Developing seven intervention packages; Step 6: Training--Post graduate diploma in clinical child development; Step 7: CDC Clinic Services--seven major ones; Step 8: CDC Community Services--Child development referral units; Step 9: Community service delivery models--Childhood disability and for adolescent care counselling projects; Step 10: National capacity building--Four child development related courses. CDC Kerala follow-up and clinic services are offered till 18 y of age and premarital counselling till 24 y of age as shown in "CDC Kerala Clinic Services Flow Chart" and 74,291 children have availed CDC clinic services in the last 10 y. CDC Kerala is the first model for comprehensive child adolescent development services using a lifecycle approach in the Government sector and hence declared as the collaborative centre for Rashtriya Bal Swasthya Karyakram (RBSK), in Kerala.

29 CFR 1910.36 - Design and construction requirements for exit routes.

Science.gov (United States)

2010-07-01

... construction requirements for exit routes. (a) Basic requirements. Exit routes must meet the following design... your workplace, consult NFPA 101-2000, Life Safety Code. (c) Exit discharge. (1) Each exit discharge... route must be adequate. (1) Exit routes must support the maximum permitted occupant load for each floor...

CDC Child Growth Charts

Data.gov (United States)

U.S. Department of Health & Human Services — CDC child growth charts consist of a series of percentile curves that illustrate the distribution of selected body measurements in U.S. children. Pediatric growth...

Fission yeast cdc24(+) encodes a novel replication factor required for chromosome integrity.

Science.gov (United States)

Gould, K L; Burns, C G; Feoktistova, A; Hu, C P; Pasion, S G; Forsburg, S L

1998-07-01

A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified previously in a screen for cell division cycle mutants and the cdc24(+) gene was determined to be essential for S phase in this yeast. We have isolated the cdc24(+) gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24(+) are inviable, indicating that cdc24(+) is an essential gene. The transcript of cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity.

CDC Best Practices for Comprehensive Tobacco Control Programs - 2007

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). Best Practices for Comprehensive Tobacco Control Programs. Funding. CDC's Best Practices for Comprehensive Tobacco...

CDC Best Practices for Comprehensive Tobacco Control Programs - 2014

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). Best Practices for Comprehensive Tobacco Control Programs. Funding. CDC's Best Practices for Comprehensive Tobacco...

Cdc45-induced loading of human RPA onto single-stranded DNA.

Science.gov (United States)

Szambowska, Anna; Tessmer, Ingrid; Prus, Piotr; Schlott, Bernhard; Pospiech, Helmut; Grosse, Frank

2017-04-07

Cell division cycle protein 45 (Cdc45) is an essential component of the eukaryotic replicative DNA helicase. We found that human Cdc45 forms a complex with the single-stranded DNA (ssDNA) binding protein RPA. Moreover, it actively loads RPA onto nascent ssDNA. Pull-down assays and surface plasmon resonance studies revealed that Cdc45-bound RPA complexed with ssDNA in the 8-10 nucleotide binding mode, but dissociated when RPA covered a 30-mer. Real-time analysis of RPA-ssDNA binding demonstrated that Cdc45 catalytically loaded RPA onto ssDNA. This placement reaction required physical contacts of Cdc45 with the RPA70A subdomain. Our results imply that Cdc45 controlled stabilization of the 8-nt RPA binding mode, the subsequent RPA transition into 30-mer mode and facilitated an ordered binding to ssDNA. We propose that a Cdc45-mediated loading guarantees a seamless deposition of RPA on newly emerging ssDNA at the nascent replication fork. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cdc15 Phosphorylates the C-terminal Domain of RNA Polymerase II for Transcription during Mitosis.

Science.gov (United States)

Singh, Amit Kumar; Rastogi, Shivangi; Shukla, Harish; Asalam, Mohd; Rath, Srikanta Kumar; Akhtar, Md Sohail

2017-03-31

In eukaryotes, the basal transcription in interphase is orchestrated through the regulation by kinases (Kin28, Bur1, and Ctk1) and phosphatases (Ssu72, Rtr1, and Fcp1), which act through the post-translational modification of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. The CTD comprises the repeated Tyr-Ser-Pro-Thr-Ser-Pro-Ser motif with potential epigenetic modification sites. Despite the observation of transcription and periodic expression of genes during mitosis with entailing CTD phosphorylation and dephosphorylation, the associated CTD specific kinase(s) and its role in transcription remains unknown. Here we have identified Cdc15 as a potential kinase phosphorylating Ser-2 and Ser-5 of CTD for transcription during mitosis in the budding yeast. The phosphorylation of CTD by Cdc15 is independent of any prior Ser phosphorylation(s). The inactivation of Cdc15 causes reduction of global CTD phosphorylation during mitosis and affects the expression of genes whose transcript levels peak during mitosis. Cdc15 also influences the complete transcription of clb2 gene and phosphorylates Ser-5 at the promoter and Ser-2 toward the 3' end of the gene. The observation that Cdc15 could phosphorylate Ser-5, as well as Ser-2, during transcription in mitosis is in contrast to the phosphorylation marks put by the kinases in interphase (G 1 , S, and G 2 ), where Cdck7/Kin28 phosphorylates Ser-5 at promoter and Bur1/Ctk1 phosphorylates Ser-2 at the 3' end of the genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The effect of DNA replication on mutation of the Saccharomyces cerevisiae CDC8 gene.

Science.gov (United States)

Zaborowska, D; Zuk, J

1990-04-01

Incubation in YPD medium under permissive conditions when DNA replication is going on, strongly stimulates the induction of cdc+ colonies of UV-irradiated cells of yeast strains HB23 (cdc8-1/cdc8-3), HB26 (cdc8-3/cdc8-3) and HB7 (cdc8-1/cdc8-1). Inhibition of DNA replication by hydroxyurea, araCMP, cycloheximide or caffeine or else by incubation in phosphate buffer pH 7.0, abolishes this stimulation. Thus the replication of DNA is strongly correlated with the high induction of cdc+ colonies by UV irradiation. It is postulated that these UV-induced cdc+ colonies arise as the result infidelity in DNA replication.

RhoA, Rac1 and Cdc42 differentially regulate aSMA and collagen I expression in mesenchymal stem cells.

Science.gov (United States)

Ge, Jianfeng; Burnier, Laurent; Adamopoulou, Maria; Kwa, Mei Qi; Schaks, Matthias; Rottner, Klemens; Brakebusch, Cord

2018-04-26

Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and descendants of it lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of αSMA, but not of collagen I α1 (col1a1). While loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect. Although actin polymerization and MRTFa were crucial for TGFβ-induced αSMA expression, neither Arp2/3 dependent actin polymerization nor cofilin dependent severing and depolymerization of F-actin were required. Instead, F-actin levels were dependent on cell contraction and TGFβ-induced actin polymerisation correlated with increased cell contraction mediated by RhoA and Cdc42. Finally, we observed impaired collagen I secretion in MSC lacking RhoA or Cdc42. These data give novel molecular insights into the role of Rho GTPases in TGFβ signaling and have implications for our understanding of MSC function in fibrosis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Dissuasive exit signage for building fire evacuation.

Science.gov (United States)

Olander, Joakim; Ronchi, Enrico; Lovreglio, Ruggiero; Nilsson, Daniel

2017-03-01

This work presents the result of a questionnaire study which investigates the design of dissuasive emergency signage, i.e. signage conveying a message of not utilizing a specific exit door. The work analyses and tests a set of key features of dissuasive emergency signage using the Theory of Affordances. The variables having the largest impact on observer preference, interpretation and noticeability of the signage have been identified. Results show that features which clearly negate the exit-message of the original positive exit signage are most effective, for instance a red X-marking placed across the entirety of the exit signage conveys a clear dissuasive message. Other features of note are red flashing lights and alternation of colour. The sense of urgency conveyed by the sign is largely affected by sensory inputs such as red flashing lights or other features which cause the signs to break the tendencies of normalcy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiation degradation of aromatic pollutants exit in wastewater and ph dependence

CERN Document Server

Takriti, S

2002-01-01

The effect of gamma radiation on the degradation of phenol (hydroxybenzene), resorcinol (1,3 dihydroxybenzen) and hydroquinone (1,4 dihydroxybenzen) exit in waste water was investigated. The concentrations of these pollutants as well as the irradiated solution ph were studied. The results showed that the phenol is very resistance against the radiation doses comparing the other phenol compounds. Phenol was also a product of radiolysis of resorcinol and hydroquinone. On the other hand, the acid phase of the irradiation sample increased the degradation rate of pollutants. Spectrophotometer (UV-VIS) and chromatography (HPLC) were used to monitor the analysis of the radiation product solution. The results illustrated the existing of many substances such as organic alcohol, aldehyde, ketone and acidic functional groups as a final radiation products. The degradation of benzene, monochlorobenzene (CB) and 1,2 dichlorobenzene (1,2 DCB) exit in waste water by gamma irradiation was investigated. The effect of the irradi...

Discovery and characterization of novel imidazopyridine derivative CHEQ-2 as a potent CDC25 inhibitor and promising anticancer drug candidate.

Science.gov (United States)

Song, Yu'ning; Lin, Xiaoqian; Kang, Dongwei; Li, Xiao; Zhan, Peng; Liu, Xinyong; Zhang, Qingzhu

2014-07-23

Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation via the interactions with CDK/Cyclin complexes. Overexpression of CDC25 proteins is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, inhibiting CDC25 activity in cancer treatment appears a good therapeutic strategy. In this article, refinement of the initial hit XDW-1 by synthesis and screening of a focused compound library led to the identification of a novel set of imidazopyridine derivatives as potent CDC25 inhibitors. Among them, the most potent molecule was CHEQ-2, which could efficiently inhibit the activities of CDC25A/B enzymes as well as the proliferation of various different types of cancer cell lines in vitro assay. Moreover, CHEQ-2 triggered S-phase cell cycle arrest in MCF-7, HepG2 and HT-29 cell lines, accompanied by generation of ROS, mitochondrial dysfunction and apoptosis. Besides, oral administration of CHEQ-2 (10 mg/kg) significantly inhibited xenografted human liver tumor growth in nude mice, while demonstrated extremely low toxicity (LD50 > 2000 mg/kg). These findings make CHEQ-2 a good starting point for further investigation and structure modification. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Cdc42-mediated tubulogenesis controls cell specification

DEFF Research Database (Denmark)

Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe

2009-01-01

Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis

Energy Technology Data Exchange (ETDEWEB)

Singh, Raman Deep, E-mail: Takhter.Ramandeep@mayo.edu; Schroeder, Andreas S.; Scheffer, Luana; Holicky, Eileen L.; Wheatley, Christine L.; Marks, David L., E-mail: Marks.david@mayo.edu; Pagano, Richard E.

2013-05-10

localize to lipid rafts and recruit cholesterol into protrusions and away from caveolae, leading to increased phosphorylation of caveolin-1, which inhibits Cdc42-dependent endocytosis. This study provides a new insight for the role for prominins in the regulation of PM lipid organization.

Histomorphometry and expression of Cdc47 and caspase-3 in hyperthyroid rat uteri and placentas during gestation and postpartum associated with fetal development.

Science.gov (United States)

Freitas, E S; Leite, E D; Souza, C A; Ocarino, N M; Ferreira, E; Cassali, G D; Gomes, M G; Serakides, R

2007-01-01

In two different experiments, the effects of hyperthyroidism on the histomorphometry and expression of Cdc47 and caspase-3 were evaluated in the uteri and placentas during gestation and postpartum. Fetal development was also evaluated during gestation. In the first experiment, 36 adult female Wistar rats were divided into two groups of 18 animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed at 7, 14 and 19 days of gestation. Uteri and placentas were weighed and subjected to histomorphometric and immunohistochemical evaluation to determine the expression of Cdc47 and caspase-3. Ovaries were also evaluated for weight and subjected to morphometric analysis. Fetuses were quantified and weighed individually. In the second experiment, 12 adult female Wistar rats were divided into two groups of six animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed 2 days postpartum. Uteri were evaluated in the same way as for the first experiment. Hyperthyroidism increased ovulation and conception rates without disturbing the size and viability of the fetuses. In the pregnant uteri, hyperthyroidism did not change the thickness of the layers or the expression of Cdc47 and caspase-3. However, in the placentas, hyperthyroidism increased the medium diameter of trophoblast cells, as well as the thickness and the expression of Cdc47 of spongiotrophoblast cells, at 14 days of gestation. During uterine involution, hyperthyroidism significantly increased the expression of Cdc47 and reduced the expression of caspase-3 in the uterine layers. In conclusion, hyperthyroidism increased the conception rate because of an ovulation gain, induced significant placental changes during pregnancy and, in the uterus, increased Cdc47 expression and decreased caspase-3 expression after parturition.

Hispanic Health: CDC Vitalsigns

Science.gov (United States)

... Injury Prevention & Control Gateway to Health Communication & Social Marketing Practice On Other Web Sites MedlinePlus – Hispanic American ... MB] en Español [PDF – 1.61 MB] CDC Digital Press Kit Read the MMWR Science Clips Language: ...

Human CDT1 associates with CDC7 and recruits CDC45 to chromatin during S phase

DEFF Research Database (Denmark)

Ballabeni, Andrea; Zamponi, Raffaela; Caprara, Greta

2009-01-01

The initiation of DNA replication is a tightly controlled process that involves the formation of distinct complexes at origins of DNA replication at specific periods of the cell cycle. Pre-Replicative Complexes are formed during telophase and early G1. They rearrange at the start of S phase to form...... pre-Initiation Complexes, which are a prerequisite for DNA replication. The CDT1 protein is required for the formation of the pre-Replicative Complexes. Here we show that human CDT1 associates with the CDC7 kinase and recruits CDC45 to chromatin. Moreover, we show that the amount of CDT1 bound...

Exit interviews to reduce turnover amongst healthcare professionals.

Science.gov (United States)

Webster, Joan; Flint, Anndrea

2014-08-19

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going studies. We did not restrict searches by language or publication date. Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no studies that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new studies. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

CDC Vital Signs–Opioid Prescribing

Centers for Disease Control (CDC) Podcasts

2017-07-06

This podcast is based on the July 2017 CDC Vital Signs report. Higher opioid prescribing puts patients at risk for addiction and overdose. Learn what can be done about this serious problem.  Created: 7/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/6/2017.

Exit examinations, peer academic climate, and adolescents' developmental outcomes.

Science.gov (United States)

Benner, Aprile D

2013-02-01

Implications of high school exit examination performance were examined with a sample of 672 racial/ethnic minority students. Exit examination failure in the 10th grade was negatively linked to subsequent grade point average, school engagement, and school belonging one year later, controlling for outcomes prior to taking the examination. Academically incongruent students-those who failed the exit examination but were in schools where their same-race/ethnicity peers were performing well academically-seemed to be at particular risk for struggling grades and poorer socioemotional well-being (e.g., experiencing greater depressive symptoms and loneliness). Findings contribute to the limited research base on exit examinations and highlight the links between exit examination performance and developmental outcomes beyond the oft-studied academic domain. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application

International Nuclear Information System (INIS)

Banjade, D.P.; Shukri, A.; Tajuddin, A.A.; Shrestha, S.L.; Bhat, M.

2002-01-01

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within ±3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at d max ). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice. Copyright (2002) Australasian College of Physical Scientists and Engineers in Medicine

Is the publication of exit poll results morally permissible?

DEFF Research Database (Denmark)

Sønderholm, Jørn

2016-01-01

This article is about exit polls. It addresses the question of whether or not it is morally permissible to publish exit poll results. The conclusion of the article is that an affirmative answer should be given to this question. In section 2, the master argument in favor of the moral permissibility...... of the publication of exit poll results is introduced. This is a strong argument. It is, however, argued that it might be the case that the conclusion of this argument should be rejected if there are other, and weightier, arguments against the idea that the publication of exit poll results is morally permissible....... In section 3, the strongest arguments against the moral permissibility of the publication of exit poll results are outlined and discussed. The conclusion of this section is that all these arguments fail in their intended purpose. The conclusion of the article is therefore justified....

CDC PRAMStat Data for 2010

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2005

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2003

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2000

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2008

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2009

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2004

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2006

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2002

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2001

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

CDC PRAMStat Data for 2007

Data.gov (United States)

U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). PRAMS, the Pregnancy Risk Assessment Monitoring System, is a surveillance system collecting state-specific,...

Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex.

Science.gov (United States)

Bodnar, Nicholas O; Rapoport, Tom A

2017-05-04

The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding. ATP hydrolysis by the D1 ring is important for subsequent substrate release from the Cdc48 complex. This release requires cooperation of Cdc48 with a deubiquitinase, which trims polyubiquitin to an oligoubiquitin chain that is then also translocated through the pore. Together, these results lead to a new paradigm for the function of Cdc48 and its mammalian ortholog p97/VCP. Copyright © 2017 Elsevier Inc. All rights reserved.

IPO as an Exit startegy in Management Buyouts

OpenAIRE

Sheth, Vidhi Chetan

2008-01-01

The basic subject to this research project is,IPO as an exit strategy in management buyouts. The paper provides with an understanding of the various characteristics and factors that have an impact on a buyout exit through an IPO. Discussions on the issues like the IPO versus other exit strategies, performance of a company's pre-IPO as well as post-IPO, the trends in the buyout and the IPO market, etc are done. For a better understanding and an in-depth knowledge about the topic, we have analy...

77 FR 19132 - Federal Motor Vehicle Safety Standards; Bus Emergency Exits and Window Retention and Release

Science.gov (United States)

2012-03-30

... Bird Body Company (Blue Bird), Thomas Built Buses (Thomas Built), the National Truck Equipment....'' (Emphasis added.) That is to say, the agency intended a window or roof exit with one release mechanism to be... make every reasonable effort to ensure that the regulation: (1) Clearly specifies the preemptive effect...

Exit by Afghanisation

DEFF Research Database (Denmark)

Holmberg, Hasse

USA’s exit-strategi fra Afghanistan har båret præg af et italesat hovedmål om overdragelse af ansvar til de nationale myndigheder i landet. Exit-strategien udmærker sig ved sin lighed med USA’s afvikling af sit engagement i Vietnam for snart et halvt århundrede siden, hvor begrebet Vietnamisation...... om national selvbestemmelse. Den amerikanske opinion spillede en afgørende rolle og afslutningen af engagementet i Vietnam kan i lige så høj grad ses som en reaktion på den massive folkelige modstand mod krigen. Omtrent 40 år efter kan Obama-administrationen notere sig en lignende negativ trend i...... Kissinger vidste, at krigen i Vietnam var tabt. Vietnamisation havde i høj grad til formål at slutte USA’s engagement på en måde, der tog hensyn til USA’s internationale renomme. Spørgsmålet er så om de mange strategiske ligheder kan overføres til samme konklusion: krigen er tabt. Briefet har til hensigt...

A study on surveillance equipment at the exit/entry control point of nuclear facility

International Nuclear Information System (INIS)

Park, C. S.; Kim, D. Y.; Cha, H. L.; Kim, H. D.; Hong, J. S.

1999-01-01

Exit/Entry control is an essential measure at both entrances of the protected area and vital area of nuclear facility at which physical protection is required under the relevant laws and regulations. Especially, when there are heavy traffics of personnel and process equipment in those areas, automated surveillance devices have to be introduced to timely and efficiently screen out internal and external adversaries from achieving their goals of stealing of nuclear material and/or sabotage of the facility. The major portion of this study involves with integration and processing of signals from radiation detector, metal detector, and image monitor. This integrated device together with positive personal identification device which will be reinforced in near future would contribute to the establishment of total exit/entry control point of nuclear facility

System integration of CDC attenuation in the new Opel Astra; Systemintegration der CDC-Daempfung beim neuen Opel Astra

Energy Technology Data Exchange (ETDEWEB)

Balandat, W.; Kutsche, T. [ZF Sachs AG, Schweinfurt (Germany)

2004-08-01

The optional carriage system IDS Plus of the new Opel Astra was developed in close cooperation between opel, ZF Sachs and other suppliers. This networking approach resulted in a high degree of system integration with the electronic attenuation control system CDC as key element. (orig.) [German] Das optionale Fahrwerksystem IDS Plus im neuen Opel Astra entstand in enger Kooperation zwischen Opel, ZF Sachs und weiteren Zulieferern. Die Arbeit im Netzwerk fuehrte zu einer hohen Systemintegration, in deren Kern die elektronische Daempferregelung CDC steht. (orig.)

Entry and exit decisions under uncertainty

DEFF Research Database (Denmark)

Kongsted, Hans Christian

1996-01-01

This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result......This paper establishes the general deterministic limit that corresponds to Dixit's model of entry and exit decisions under uncertainty. The interlinked nature of decisions is shown to be essential also in the deterministic limit. A numerical example illustrates the result...

S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

Science.gov (United States)

Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

2018-05-04

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

The human homolog of S. cerevisiae CDC27, CDC27 Hs, is encoded by a highly conserved intronless gene present in multiple copies in the human genome

Energy Technology Data Exchange (ETDEWEB)

Devor, E.J.; Dill-Devor, R.M. [Univ. of Iowa College of Medicine, Iowa City (United States)

1994-09-01

We have obtained a number of unique sequences via PCR amplification of human genomic DNA using degenerate primers under low stringency (42{degrees}C). One of these, an 853 bp product, has been identified as a partial genomic sequence of the human homolog of the S. cerevisiae CDC27 gene, CDC27Hs (GenBank No. U00001). This gene, reported by Turgendreich et al. is also designated EST00556 from Adams et al. We have undertaken a more detailed examination of our sequence, MCP34N, and have found that: 1. the genomic sequence is nearly identical to CDC27Hs over its entire 853 bp length; 2. an MCP34N-specific PCR assay of several non-human primate species reveals amplification products in chimpanzee and gorilla genomes having greater than 90% sequence identity with CDC27Hs; and 3. an MCP34N-specific PCR assay of the BIOS hybrid cell line panel gives a discordancy pattern suggesting multiple loci. Based upon these data, we present the following initial characterization: 1. the complete MCP34N sequence identity with CDC27Hs indicates that the latter is encoded by an intronless gene; 2. CDC27Hs is highly conserved among higher primates; and 3. CDC27Hs is present in multiple copies in the human genome. These characteristics, taken together with those initially reported for CDC27Hs, suggest that this is an old gene that carries out an important but, as yet, unknown function in the human brain.

CDC Vital Signs–HIV Testing

Centers for Disease Control (CDC) Podcasts

2017-11-28

This podcast is based on the December 2017 CDC Vital Signs report. In the U.S., about 15 percent of people who have HIV don't know they have it. Learn about the importance of testing, early diagnosis, and treatment.  Created: 11/28/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 11/28/2017.

CDC's 29th Annual Joseph W. Mountin Lecture

Centers for Disease Control (CDC) Podcasts

In this podcast, William H. Foege, MD, MPH delivers the 29th Annual Joseph W. Mountin Lecture. Dr. Foege was a key leader in the smallpox effort and worked as an epidemiologist in the successful eradication campaign in the 1970s. Dr. Foege became chief of the Smallpox Eradication Program at CDC, and was appointed director of CDC in 1977.

Jet Exit Rig Six Component Force Balance

Science.gov (United States)

Castner, Raymond; Wolter, John; Woike, Mark; Booth, Dennis

2012-01-01

A new six axis air balance was delivered to the NASA Glenn Research Center. This air balance has an axial force capability of 800 pounds, primary airflow of 10 pounds per second, and a secondary airflow of 3 pounds per second. Its primary use was for the NASA Glenn Jet Exit Rig, a wind tunnel model used to test both low-speed, and high-speed nozzle concepts in a wind tunnel. This report outlines the installation of the balance in the Jet Exit Rig, and the results from an ASME calibration nozzle with an exit area of 8 square-inches. The results demonstrated the stability of the force balance for axial measurements and the repeatability of measurements better than 0.20 percent.

Criticality safety analysis of a calciner exit chute

International Nuclear Information System (INIS)

Haught, C.F.; Basoglu, B.; Brewer, R.W.; Hollenback, D.F.; Wilkinson, A.D.; Dodds, H.L.

1994-01-01

Calcination of uranyl nitrate into uranium oxide is part of normal operations of some enrichment plants. Typically, a calciner discharges uranium oxide powder (U 3 O 8 ) into an exit chute that directs the powder into a receiving can located in a glove box. One possible scenario for a criticality accident is the exit chute becoming blocked with powder near its discharge. The blockage restricts the flow of powder causing the exit chute to become filled with the powder. If blockage does occur, the height of the powder could reach a level that would not be safe from a criticality point of view. In this analysis, the subcritical height limit is examined for 98% enriched U 3 O 8 in the exit chute with full water reflection and optimal water moderation. The height limit for ensuring criticality safety during such an accumulation is 28.2 cm above the top of the discharge pipe at the bottom of the chute. Chute design variations are also evaluated with full water reflection and optimal water moderation. Subcritical configurations for the exit chute variation are developed, but the configurations are not safe when combined with the calciner. To ensure criticality safety, modifications must be made to the calciner tube or safety measures must be implemented if these designs are to be utilized with 98% enriched material. A geometrically safe configuration for the exit chute is developed for a blockage of 20% enriched powder with full water reflection and optimal water moderation, and this configuration is safe when combined with the existing calciner

The Ubiquitin-Specific Protease 14 (USP14) Is a Critical Regulator of Long-Term Memory Formation

Science.gov (United States)

Jarome, Timothy J.; Kwapis, Janine L.; Hallengren, Jada J.; Wilson, Scott M.; Helmstetter, Fred J.

2014-01-01

Numerous studies have suggested a role for ubiquitin-proteasome-mediated protein degradation in learning-dependent synaptic plasticity; however, very little is known about how protein degradation is regulated at the level of the proteasome during memory formation. The ubiquitin-specific protease 14 (USP14) is a proteasomal deubiquitinating enzyme…

CDC WONDER: Mortality - Infant Deaths

Data.gov (United States)

U.S. Department of Health & Human Services — The Mortality - Infant Deaths (from Linked Birth / Infant Death Records) online databases on CDC WONDER provide counts and rates for deaths of children under 1 year...

Fisetin induces G2/M phase cell cycle arrest by inactivating cdc25C-cdc2 via ATM-Chk1/2 activation in human endometrial cancer cells

Directory of Open Access Journals (Sweden)

Zhan-Ying Wang

2015-06-01

Full Text Available Endometrial cancer is one of the most prevalent gynaecological malignancies where, currently available therapeutic options remain limited. Recently phytochemicals are exploited for their efficiency in cancer therapy. The present study investigates the anti-proliferative effect of fisetin, a flavonoid on human endometrial cancer cells (KLE and Hec1 A. Fisetin (20-100 µM effectively reduced the viability of Hec1 A and KLE cells and potentially altered the cell population at G2/M stage. Expression levels of the cell cycle proteins (cyclin B1, p-Cdc2, p-Cdc25C, p-Chk1, Chk2, p-ATM, cyclin B1, H2AX, p21 and p27 were analyzed. Fisetin suppressed cyclin B1 expression and caused inactiva-tion of Cdc25C and Cdc2 by increasing their phosphorylation levels and further activated ATM, Chk1 and Chk2. Increased levels of p21 and p27 were observed as well. These results suggest that fisetin induced G2/M cell cycle arrest via inactivating Cdc25c and Cdc2 through activation of ATM, Chk1 and Chk2.

24 CFR 3280.106 - Exit facilities; egress windows and devices.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Exit facilities; egress windows and... § 3280.106 Exit facilities; egress windows and devices. (a) Every room designed expressly for sleeping purposes, unless it has an exit door (see § 3280.105), shall have at least one outside window or approved...

An Identity Theory of Role Exit among Soccer Referees

OpenAIRE

Milne, Jason Syme

2006-01-01

This study examines how identity processes affect role exit. I test a model of role exit that situates the identity processes of cognitive processes (reflected appraisals and social comparisons), rewards and costs related to the role, commitment to the role, and identity centrality as mediating factors between role-set and social characteristic background factors, and role exit. Using a sample of 940 current and former soccer referees in Virginia and the District of Columbia, the results s...

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

Science.gov (United States)

Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

2008-01-01

Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.

Science.gov (United States)

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-07-08

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

CDC Vital Signs: Preventing Melanoma

Science.gov (United States)

... not use the device. Include warning statements in marketing materials about the risk of using the device. ... MB] en Español [PDF – 1.16 MB] CDC Digital Press Kit Read the MMWR Science Clips Language: ...

The G2/M DNA damage checkpoint inhibits mitosis through Tyr15 phosphorylation of p34cdc2 in Aspergillus nidulans.

Science.gov (United States)

Ye, X S; Fincher, R R; Tang, A; Osmani, S A

1997-01-02

It is possible to cause G2 arrest in Aspergillus nidulans by inactivating either p34cdc2 or NIMA. We therefore investigated the negative control of these two mitosis-promoting kinases after DNA damage. DNA damage caused rapid Tyr15 phosphorylation of p34cdc2 and transient cell cycle arrest but had little effect on the activity of NIMA. Dividing cells deficient in Tyr15 phosphorylation of p34cdc2 were sensitive to both MMS and UV irradiation and entered lethal premature mitosis with damaged DNA. However, non-dividing quiescent conidiospores of the Tyr15 mutant strain were not sensitive to DNA damage. The UV and MMS sensitivity of cells unable to tyrosine phosphorylate p34cdc2 is therefore caused by defects in DNA damage checkpoint regulation over mitosis. Both the nimA5 and nimT23 temperature-sensitive mutations cause an arrest in G2 at 42 degrees C. Addition of MMS to nimT23 G2-arrested cells caused a marked delay in their entry into mitosis upon downshift to 32 degrees C and this delay was correlated with a long delay in the dephosphorylation and activation of p34cdc2. Addition of MMS to nimA5 G2-arrested cells caused inactivation of the H1 kinase activity of p34cdc2 due to an increase in its Tyr15 phosphorylation level and delayed entry into mitosis upon return to 32 degrees C. However, if Tyr15 phosphorylation of p34cdc2 was prevented then its H1 kinase activity was not inactivated upon MMS addition to nimA5 G2-arrested cells and they rapidly progressed into a lethal mitosis upon release to 32 degrees C. Thus, Tyr15 phosphorylation of p34cdc2 in G2 arrests initiation of mitosis after DNA damage in A. nidulans.

Exit channels of autoionization resonances in atoms

International Nuclear Information System (INIS)

Krause, M.O.

1985-01-01

In many-electron atoms with open shells strong autoionization resonances occur when an electron from an inner, weakly bound subshell is excited. Usually, the resonance state lies above several ionization thresholds and, hence, will decay into more than one exit or continuum channel. Several cases are discussed in which the resonance state is induced by synchrotron radiation, and the exit channels are differentiated and characterized by the analysis of the ejected electrons

CDC Vital Signs: Hispanic Health

Science.gov (United States)

... Injury Prevention & Control Gateway to Health Communication & Social Marketing Practice On Other Web Sites MedlinePlus – Hispanic American ... MB] en Español [PDF – 1.61 MB] CDC Digital Press Kit Read the MMWR Science Clips Language: ...

CDC Lab Values

Centers for Disease Control (CDC) Podcasts

More than fifteen hundred scientists fill the lab benches at CDC, logging more than four million hours each year. CDC’s laboratories play a critical role in the agency’s ability to find, stop, and prevent disease outbreaks. This podcast provides a brief overview of what goes on inside CDC’s labs, and why this work makes a difference in American’s health.

CDC Vital Signs-HIV Testing

Centers for Disease Control (CDC) Podcasts

This podcast is based on the December 2017 CDC Vital Signs report. In the U.S., about 15 percent of people who have HIV don't know they have it. Learn about the importance of testing, early diagnosis, and treatment.

CDC Vital Signs-Legionnaires' Disease

Centers for Disease Control (CDC) Podcasts

This podcast is based on the June 2017 CDC Vital Signs report. Legionnaires' disease is a serious, often deadly lung infection. People most commonly get it by breathing in water droplets containing Legionella germs. Learn how to prevent infections from Legionella.

Turbine-missile casing exit tests

International Nuclear Information System (INIS)

Yoshimura, H.R.; Sliter, G.E.

1978-01-01

Nuclear power plant designers are required to provide safety-related components with adequate protection against hypothetical turbine-missile impacts. In plants with a ''peninsula'' arrangement, protection is provided by installing the turbine axis radially from the reactor building, so that potential missile trajectories are not in line with the plant. In plants with a ''non-peninsula'' arrangement (turbine axis perpendicular to a radius), designers rely on the low probability of a missile strike and on the protection provided by reinforced concrete walls in order to demonstrate an adequate level of protection USNRC Regulatory Guide 1.115). One of the critical first steps in demonstrating adequacy is the determination of the energy and spin of the turbine segments as they exit the turbine casing. The spin increases the probability that a subsequent impact with a protective barrier will be off-normal and therefore less severe than the normal impact assumed in plant designs. Two full-scale turbine-missile casing exit tests which were conducted by Sandia Laboratories at their rocket-sled facility in Albuquerque, New Mexico, are described. Because of wide variations in turbine design details, postulated failure conditions, and missile exit scenarios, the conditions for the two tests were carefully selected to be as prototypical as possible, while still maintaining the well-controlled and well-characterized test conditions needed for generating benchmark data

Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex.

Science.gov (United States)

Clément, Olivier; Hemming, Isabel Anne; Gladwyn-Ng, Ivan Enghian; Qu, Zhengdong; Li, Shan Shan; Piper, Michael; Heng, Julian Ik-Tsen

2017-05-15

During the development of the mammalian cerebral cortex, newborn postmitotic projection neurons are born from local neural stem cells and must undergo radial migration so as to position themselves appropriately to form functional neural circuits. The zinc finger transcriptional repressor Rp58 (also known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its underlying molecular mechanism remains to be better characterised. Here, we demonstrate that the co-expression of Rp58 and the cyclin dependent kinase inhibitor (CDKI) p27 kip1 is important for E14.5-born cortical neurons to coordinate cell cycle exit and initiate their radial migration. Notably, we find that the impaired radial positioning of Rp58-deficient cortical neurons within the embryonic (E17.5) mouse cortex, as well as their multipolar to bipolar transition from the intermediate zone to the cortical plate can be restored by forced expression of p27 kip1 in concert with suppression of Rnd2, a downstream target gene of Rp58. Furthermore, the restorative effects of p27 kip1 and Rnd2 abrogation are reminiscent of suppressing RhoA signalling in Rp58-deficient cells. Our findings demonstrate functional interplay between a transcriptional regulator and a CDKI to mediate neuroprogenitor cell cycle exit, as well as to promote radial migration through a molecular mechanism consistent with suppression of RhoA signalling.

Entry and Exit.

Science.gov (United States)

1987-03-01

1. Introduction R Analyses of industrial competition have attained a new vigor with the application of game -theoretic methods. The process of... competition is represented in models that reflect genuine struggles for entry, market power, and continuing survival. Dynamics and informational effects are...presents a few of the models developed recently to study competitive processes that affect a firm’s entry into a market , and the decision to exit. The

Exiting and Returning to the Parental Home for Boomerang Kids.

Science.gov (United States)

Sandberg-Thoma, Sara E; Snyder, Anastasia R; Jang, Bohyun Joy

2015-06-01

Young adults commonly exit from and return to the parental home, yet few studies have examined the motivation behind these exits and returns using a life course framework. Using data from the National Longitudinal Survey of Youth 1997, the authors examined associations between mental health problems and economic characteristics and exits from (n = 8,162), and returns to (n = 6,530), the parental home during the transition to adulthood. The average age of the respondents was 24 years. The authors found evidence that mental health and economic characteristics were related to home leaving and returning. Emotional distress was associated with earlier exits from, and returns to, the parental home; alcohol problems were associated with earlier returns to the parental home. The findings regarding economic resources were unexpectedly mixed. Greater economic resources were linked to delayed exits from, and earlier returns to, the parental home. The implications of these findings for young adults are discussed.

Cell cycle-dependent mobility of Cdc45 determined in vivo by fluorescence correlation spectroscopy.

Directory of Open Access Journals (Sweden)

Ronan Broderick

Full Text Available Eukaryotic DNA replication is a dynamic process requiring the co-operation of specific replication proteins. We measured the mobility of eGFP-Cdc45 by Fluorescence Correlation Spectroscopy (FCS in vivo in asynchronous cells and in cells synchronized at the G1/S transition and during S phase. Our data show that eGFP-Cdc45 mobility is faster in G1/S transition compared to S phase suggesting that Cdc45 is part of larger protein complex formed in S phase. Furthermore, the size of complexes containing Cdc45 was estimated in asynchronous, G1/S and S phase-synchronized cells using gel filtration chromatography; these findings complemented the in vivo FCS data. Analysis of the mobility of eGFP-Cdc45 and the size of complexes containing Cdc45 and eGFP-Cdc45 after UVC-mediated DNA damage revealed no significant changes in diffusion rates and complex sizes using FCS and gel filtration chromatography analyses. This suggests that after UV-damage, Cdc45 is still present in a large multi-protein complex and that its mobility within living cells is consistently similar following UVC-mediated DNA damage.

CDC Vital Signs–Preventing Stroke Deaths

Centers for Disease Control (CDC) Podcasts

2017-09-06

This podcast is based on the September 2017 CDC Vital Signs report. Each year, more than 140,000 people die and many survivors face disability. Eighty percent of strokes are preventable. Learn the signs of stroke and how to prevent them.  Created: 9/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 9/6/2017.

CDC STATE System Tobacco Legislation - Preemption

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Preemption. The STATE...

Shored gunshot wound of exit. A phenomenon with identity crisis.

Science.gov (United States)

Aguilar, J C

1983-09-01

Shored gunshot wound of exit is produced when the outstretched skin is impaled, sandwiched, and crushed between the outgoing bullet and the unyielding object over the exit site, thus leaving an abrasion collar on the wound margin. Proper coaptation of the wound margin is impossible because of the loss of skin just like those observed in entrance wounds. In contrast to the entrance wound, the supported exit wound shows a scalloped or punched-out abrasion collar and sharply contoured skin in between the radiating skin lacerations marginating the abrasion (Fig. 1). Should gunpowder be observed around the exit site, it is often unevenly distributed, and is not associated with searing, gunpowder stippled abrasion, tatooing, and deposition of soot.

Stalking SARS: CDC at Work

Centers for Disease Control (CDC) Podcasts

2014-05-22

In this podcast for kids, the Kidtastics talk about the SARS outbreak and how CDC worked to solve the mystery.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

Caffeine stabilizes Cdc25 independently of Rad3 in S chizosaccharomyces pombe contributing to checkpoint override

Science.gov (United States)

Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per

2014-01-01

Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325

CDC STATE System Tobacco Legislation - Licensure

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Licensure. The STATE System...

CDC STATE System Tobacco Legislation - Tax

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation-Tax. The STATE System...

CDC STATE System Tobacco Legislation - Tax

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation-Tax. The STATE System...

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

Science.gov (United States)

Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

2018-01-17

Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Exit and Voice: Organizational Loyalty and Dispute Resolution Strategies

Science.gov (United States)

Hoffmann, Elizabeth A.

2006-01-01

This study compares workplace dispute resolution strategies (exit, voice and toleration) in matched pairs of conventional and worker-owned cooperative organizations operating in three industries--coal mining, taxicab driving and organic food distribution. Building on Hirschman's classic exit, voice and loyalty thesis, this research demonstrates…

Lingering illness or sudden death? Pre-exit employment developments in German establishments

OpenAIRE

Fackler, Daniel; Schnabel, Claus; Wagner, Joachim

2012-01-01

Using a large administrative dataset for Germany, this paper compares employment developments in exiting and surviving establishments. For both West and East Germany we find a clear 'shadow of death' effect reflecting lingering illness: establishments shrink dramatically already several years before closure, employment growth rates differ strongly between exiting and surviving establishments, and this difference becomes stronger as exit approaches. We further show that prior to exit the workf...

CDC Vital Signs-Heroin Epidemic

Centers for Disease Control (CDC) Podcasts

This podcast is based on the July 2015 CDC Vital Signs report. Heroin use and heroin-related overdose deaths are increasing. Most people are using it with other drugs, especially prescription opioid painkillers. Learn what can be done to prevent and treat the problem.

Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung Min; Yamada, Masayuki; Masai, Hisao

2003-11-27

Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can generate DNA replication checkpoint signals. Efficient removal of those cells in which replication has been perturbed, through cell death, may be beneficial to maintain the highest level of genetic integrity in totipotent stem cells. Partial, rather than total, loss of Cdc7 kinase expression results in retarded growth at both cellular and whole body levels, with especially profound impairment of germ cell development.

Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development

International Nuclear Information System (INIS)

Kim, Jung Min; Yamada, Masayuki; Masai, Hisao

2003-01-01

Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can generate DNA replication checkpoint signals. Efficient removal of those cells in which replication has been perturbed, through cell death, may be beneficial to maintain the highest level of genetic integrity in totipotent stem cells. Partial, rather than total, loss of Cdc7 kinase expression results in retarded growth at both cellular and whole body levels, with especially profound impairment of germ cell development

Perseguir al SRAG: CDC en acción (Stalking SARS: CDC at Work)

Centers for Disease Control (CDC) Podcasts

2013-04-29

En este podcast los niños de Kidtastics hablan sobre el brote del SRAS y cómo trabajaron los CDC para resolver el misterio.  Created: 4/29/2013 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 8/10/2016.

UPEML, Computer Independent Emulator of CDC Update Utility

International Nuclear Information System (INIS)

2002-01-01

1 - Description of program or function: UPEML is a machine-portable CDC UPDATE emulation program. It is capable of emulating a significant subset of the standard CDC UPDATE functions, including program library creation and subsequent modification. 2 - Method of solution: UPEML was originally written to facilitate the use of CDC-based scientific packages on alternate computers. In addition to supporting computers such as the VAX/VMS, IBM, and CRAY/COS, Version 3.0 now supports UNIX workstations and the CRAY/UNICOS operating system. Several program bugs have been corrected in Version 3.0. Version 3.0 has several new features including 1) improved error checking, 2) the ability to use *ADDFILE and READ from nested files, 3) creation of compile file on creation, 4) allows identifiers to begin with numbers, and 5) ability to control warning messages and program termination on error conditions. 3 - Restrictions on the complexity of the problem: None noted

CDC WONDER: Daily Fine Particulate Matter

Data.gov (United States)

U.S. Department of Health & Human Services — The Daily Fine Particulate Matter data available on CDC WONDER are geographically aggregated daily measures of fine particulate matter in the outdoor air, spanning...

Analysis of unexpected exits using the Fokker - Planck equation

NARCIS (Netherlands)

Herwaarden, van O.A.

1996-01-01

In this thesis exit problems are considered for stochastic dynamical systems with small random fluctuations. We study exit from a domain in the state space through a boundary, or a specified part of the boundary, that is unattainable in the underlying deterministic system. We analyze

14 CFR 1310.11 - Regulations of the Office of Management and Budget.

Science.gov (United States)

2010-01-01

... Budget. (a) The regulations in this part supplement the regulations of the Office of Management and... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Regulations of the Office of Management and Budget. 1310.11 Section 1310.11 Aeronautics and Space AIR TRANSPORTATION SYSTEM STABILIZATION AIR...

Podocyte-specific loss of cdc42 leads to congenital nephropathy

DEFF Research Database (Denmark)

Scott, Rizaldy P; Hawley, Steve P; Ruston, Julie

2012-01-01

in the absence of Cdc42, indicating a disruption of the slit diaphragm. Kidneys from Rac1- and RhoA-mutant mice, however, had normal glomerular morphology and intact foot processes. A nephrin clustering assay suggested that Cdc42 deficiency, but not Rac1 or RhoA deficiency, impairs the polymerization of actin...

CDC WONDER: AIDS Public Use Data

Data.gov (United States)

U.S. Department of Health & Human Services — The AIDS Public Information Data Set (APIDS) for years 1981-2002 on CDC WONDER online database contains counts of AIDS (Acquired Immune Deficiency Syndrome) cases...

Going, Going, Gone. Innovation and Exit in Manufacturing Firms

NARCIS (Netherlands)

E. Cefis (Elena); O. Marsili (Orietta)

2007-01-01

textabstractThis paper examines the effect of innovation on the risk of exit of a firm, distinguishing between different modes of exits. Innovation represents a resource and a capability that helps a firm to build competitive advantage and remain in the market. At the same time, the resources and

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

International Nuclear Information System (INIS)

Lee, Seung Joon; Langhans, Sigrid A

2012-01-01

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Directory of Open Access Journals (Sweden)

Lee Seung Joon

2012-01-01

Full Text Available Abstract Background Curcumin (diferuloylmethane, the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC, is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Methods Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. Results We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. Conclusions We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Science.gov (United States)

2012-01-01

Background Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Methods Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. Results We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. Conclusions We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin. PMID:22280307

Comparison of sources of exit fluence variation for IMRT

International Nuclear Information System (INIS)

Gardner, Joseph K; Gordon, J James; Wang Song; Siebers, Jeffrey V; Clews, Luke; Greer, Peter B

2009-01-01

The fluence exiting a patient during beam delivery can be used as treatment delivery quality assurance, either by direct comparison with expected exit fluences or by backprojection to reconstruct the patient dose. Multiple possible sources of measured exit fluence deviations exist, including changes in the beam delivery and changes in the patient anatomy. The purpose of this work is to compare the deviations caused by these sources. Machine delivery-related variability is measured by acquiring multiple dosimetric portal images (DPIs) of several test fields without a patient/phantom in the field over a time period of 2 months. Patient anatomy-related sources of fluence variability are simulated by computing transmission DPIs for a prostate patient using the same incident fluence for 11 different computed tomography (CT) images of the patient anatomy. The standard deviation (SD) and maximum deviation of the exit fluence, averaged over 5 mm x 5 mm square areas, is calculated for each test set. Machine delivery fluence SDs as large as 1% are observed for a sample patient field and as large as 2.5% for a picket-fence dMLC test field. Simulations indicate that day-to-day patient anatomy variations induce exit fluence SDs as large as 3.5%. The largest observed machine delivery deviations are 4% for the sample patient field and 7% for the picket-fence field, while the largest difference for the patient anatomy-related source is 8.5%. Since daily changes in patient anatomy can result in substantial exit fluence deviations, care should be taken when applying fluence back-projection to ensure that such deviations are properly attributed to their source. (note)

CDC Vital Signs–Cancer and Obesity

Centers for Disease Control (CDC) Podcasts

2017-10-04

This podcast is based on the October 2017 CDC Vital Signs report. Obesity is a leading cancer risk factor. Unfortunately, two out of three U.S. adults weigh more than recommended. Find out what can be done to help people get to and keep a healthy weight.  Created: 10/4/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 10/4/2017.

Using an electronic portal imaging device for exit dose measurements in radiotherapy

International Nuclear Information System (INIS)

Ganowicz, M.; Wozniak, B.; Bekman, A.; Maniakowski, Z.

2003-01-01

To present a method of determining the exit dose with the use of an electronic portal imaging device (EPID). The device used was the Portal Vision LC250 (Varian). The EPID signals on the central beam axis have been related to the exit dose. The exit dose measurements were performed with the ionisation chamber in the slab phantom at the distance of dose maximum from the exit surface of the phantom. EPID reading was investigated as a function of field size, phantom thickness and source-detector distance. The relation between dose rate and the EPID reading is described with empirical functions applicable to the obtained data. The exit dose is calculated from the EPID reading as a product of the calibration factor and appropriate correction factors. The determination of the exit dose rate from the EPID signal requires the knowledge of many parameters and earlier determination of essential characteristics. (author)

Communications and Web services: What do CDC users desire in partner relationship management and does CDC's PHIN Directory meet the need?

Science.gov (United States)

Cervone, Maria A; Savel, Thomas G

2006-01-01

The National Center on Birth Defects and Developmental Disabilities (NCBDDD) at the Centers for Disease Control and Prevention (CDC) sought to establish a database to proactively manage their partner relationships with external organizations. A user needs analysis was conducted, and CDC's Public Health Information Network Directory (PHINDIR) was evaluated as a possible solution. PHINDIR could sufficiently maintain contact information but did not address customer relationships; however, its flexible architecture allows add-on applications via web services. Thus, NCBDDD's needs could be met via PHINDIR.

Cdc7 is required throughout the yeast S phase to activate replication origins.

Science.gov (United States)

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

Involvement of the Cdc42 pathway in CFTR post-translational turnover and in its plasma membrane stability in airway epithelial cells.

Directory of Open Access Journals (Sweden)

Romain Ferru-Clément

Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR is a chloride channel that is expressed on the apical plasma membrane (PM of epithelial cells. The most common deleterious allele encodes a trafficking-defective mutant protein undergoing endoplasmic reticulum-associated degradation (ERAD and presenting lower PM stability. In this study, we investigated the involvement of the Cdc42 pathway in CFTR turnover and trafficking in a human bronchiolar epithelial cell line (CFBE41o- expressing wild-type CFTR. Cdc42 is a small GTPase of the Rho family that fulfils numerous cell functions, one of which is endocytosis and recycling process via actin cytoskeleton remodelling. When we treated cells with chemical inhibitors such as ML141 against Cdc42 and wiskostatin against the downstream effector N-WASP, we observed that CFTR channel activity was inhibited, in correlation with a decrease in CFTR amount at the cell surface and an increase in dynamin-dependent CFTR endocytosis. Anchoring of CFTR to the cortical cytoskeleton was then presumably impaired by actin disorganization. When we performed siRNA-mediated depletion of Cdc42, actin polymerization was not impacted, but we observed actin-independent consequences upon CFTR. Total and PM CFTR amounts were increased, resulting in greater activation of CFTR. Pulse-chase experiments showed that while CFTR degradation was slowed, CFTR maturation through the Golgi apparatus remained unaffected. In addition, we observed increased stability of CFTR in PM and reduction of its endocytosis. This study highlights the involvement of the Cdc42 pathway at several levels of CFTR biogenesis and trafficking: (i Cdc42 is implicated in the first steps of CFTR biosynthesis and processing; (ii it contributes to the stability of CFTR in PM via its anchoring to cortical actin; (iii it promotes CFTR endocytosis and presumably its sorting toward lysosomal degradation.

CDC Vital Signs–Safe Sleep for Babies

Centers for Disease Control (CDC) Podcasts

2018-01-09

This podcast is based on the January 2018 CDC Vital Signs report. Every year, there are about 3,500 sleep-related deaths among U.S. babies. Learn how to create a safe sleep environment for babies.  Created: 1/9/2018 by Centers for Disease Control and Prevention (CDC).   Date Released: 1/9/2018.

Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents

International Nuclear Information System (INIS)

Aressy, B.; Bugler, B.; Valette, A.; Ducommun, B.; Biard, D.

2008-01-01

CDC25B, one of the three members of the CDC25 dual-specificity phosphatase family, plays a critical role in the control of the cell cycle and in the checkpoint response to DNA damage. CDC25B is responsible for the initial dephosphorylation and activation of the cyclin-dependent kinases, thus initiating the train of events leading to entry into mitosis. The critical role played by CDC25B is illustrated by the fact that it is specifically required for checkpoint recovery and that unscheduled accumulation of CDC25B is responsible for illegitimate entry into mitosis. Here, we report that in p53 colon carcinoma cells, a moderate increase in the CDC25B level is sufficient to impair the DNA damage checkpoint, to increase spontaneous mutagenesis, and to sensitize cells to ionising radiation and genotoxic agents. Using a tumour cell spheroid assay as an alternative to animal studies, we demonstrate that the level of CDC25B expression modulates growth inhibition and apoptotic death. Since CDC25B overexpression has been observed in a significant number of human cancers, including colon carcinoma, and is often associated with high grade tumours and poor prognosis, our work suggests that the expression level of CDC25B might be a potential key parameter of the cellular response to cancer therapy. (authors)

The determinants of firm exit in the French food industries

OpenAIRE

Blanchard, Pierre; Mathieu, Claude

2012-01-01

A semi-parametric approach is used to estimate firm propensity to exit. The unobserved individual productivity of a firm is first estimated using the Ackerberg et al. (2006) approach and then introduced as a determinant of firm exit in conjunction with other variables that may serve as barriers to exit, including the firm’s level of sunk costs and the industry concentration. Using an unbalanced panel of data for 5,849 firms in French food industries from 1996 to 2002, we find a signifi...

The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas

International Nuclear Information System (INIS)

Wang, Zhihui; Tropè, Claes G; Suo, Zhenhe; Trøen, Gunhild; Yang, Guanrui; Nesland, Jahn M; Holm, Ruth

2008-01-01

14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown. We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome. In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p = 0.001, p = 0.002 and p = 0.001, respectively) and deep invasion (p = 0.01, p = 0.001 and p = 0.007, respectively). Variations of 14-3-3σ protein expression were not associated to disease-specific survival. Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis

Congenital Cervical Teratoma: Anaesthetic Management (The EXIT Procedure

Directory of Open Access Journals (Sweden)

Ferruh Bilgin

2009-01-01

Full Text Available Ex utero intrapartum treatment (EXIT is a procedure performed during caesarean section with preservation of fetal-placental circulation, which allows the safe handling of fetal airways with risk of airways obstruction. This report aimed at describing a case of anaesthesia for EXIT in a fetus with cervical teratoma. A 30-year-old woman, 70 kg, 160 cm, gravida 2, para 1, was followed because of polyhydramniosis diagnosed at 24 weeks′ gestation. During a routine ultrasonographic examination at 35 weeks′ gestation, it was noticed that the fetus had a tumoral mass on the anterior neck, the mass had cystic and calcified components and with a size of was 10 x 6 x5 cm. The patient with physical status ASA I, was submitted to caesarean section under general anaesthesia with mechanically controlled ventilation for exutero intrapartum treatment (EXIT. Anaesthesia was induced in rapid sequence with fentanyl, propofol and rocuronium and was maintained with isoflurane in 2.5 at 3 % in O 2 and N 2 O (50%. After hysterotomy, fetus was partially released assuring uterus-placental circulation, followed by fetal laryngoscopy and tracheal intuba-tion. The infant was intubated with an uncuffed, size 2.5 endotracheal tube. Excision of the mass was performed under general anaesthesia. After surgical intervention, on the fourth postoperative day, the infant was extubated and the newborn was discharged to the pediatric neonatal unit and on the seventh day postoperatively to home without complications. Major recommendations for EXIT are maternal-fetal safety, uterine relaxation to maintain uterine volume and uterus-placental circulation, and fetal immobility to help airway handling. We report one case of cervical teratoma managed successfully with EXIT procedure.

The Effect of Exit Strategy on Optimal Portfolio Selection with Birandom Returns

Directory of Open Access Journals (Sweden)

Guohua Cao

2013-01-01

Full Text Available The aims of this paper are to use a birandom variable to denote the stock return selected by some recurring technical patterns and to study the effect of exit strategy on optimal portfolio selection with birandom returns. Firstly, we propose a new method to estimate the stock return and use birandom distribution to denote the final stock return which can reflect the features of technical patterns and investors' heterogeneity simultaneously; secondly, we build a birandom safety-first model and design a hybrid intelligent algorithm to help investors make decisions; finally, we innovatively study the effect of exit strategy on the given birandom safety-first model. The results indicate that (1 the exit strategy affects the proportion of portfolio, (2 the performance of taking the exit strategy is better than when the exit strategy is not taken, if the stop-loss point and the stop-profit point are appropriately set, and (3 the investor using the exit strategy become conservative.

CDC Vital Signs–African American Health

Centers for Disease Control (CDC) Podcasts

2017-05-02

This podcast is based on the May 2017 CDC Vital Signs report. The life expectancy of African Americans has improved, but it’s still an average of four years less than whites. Learn what can be done so all Americans can have the opportunity to pursue a healthy lifestyle.  Created: 5/2/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 5/2/2017.

30 CFR 56.4530 - Exits.

Science.gov (United States)

2010-07-01

... Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Fire Prevention and Control... a sufficient number of exits to permit prompt escape in case of fire. ...

CDC Vital Signs-Preventing Melanoma

Centers for Disease Control (CDC) Podcasts

This podcast is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.

Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development

DEFF Research Database (Denmark)

Wu, Xunwei; Li, Shaohua; Chrostek-Grashoff, Anna

2007-01-01

To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane, but exhi......To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane...

STIMULATION METHODS IMPROVEMENT OF EXIT ROUTE ON RAILWAY TRANSPORT

Directory of Open Access Journals (Sweden)

A. I. Verlan

2014-01-01

Full Text Available Purpose. The purpose of the article is to assess the costs, which are redistributed in the system «shipper−railroad−consignee» during routing of rail transportation and the development of tariff simulation methods of shippers to the exit routes formation. Methodology. Using economic and mathematical analysis the distribution of costs among the various participants of transportation process during the exit routes formation is investigated in the article. Findings. For implementation of the tariff simulation methods of exit routes and retention of the existing tariff structure it is proposed to provide in the «Tariff catalogue for freight transportation by railway transport of Ukraine» the discount, differentiated from haulage distance. A new method for determining the fees amount for cars supply and removal on approach tracks by train locomotives was also offered. Originality. As a result of the research a new method for determination of the exit rout efficiency that, unlike the existing one, takes into account the various interests of the individual participants in the transportation process was proposed. The dependence of the correction factors to the tariff for freight transportation in their own cars by direct exit routes from distance haulage was obtained. Implementation of these coefficients provides an approximation of railway tariffs to the traffic handling costs. A method for determination the rate of fees for cars supply and removal on approach tracks by train locomotives was offered. Practical value. InUkraine creation of the tariff discounts system for freight transportation by exit routes consistent with international practice and allows bringing the tariff to the real traffic handling cost. This change on the one hand will provide stimulation for private capital investments in infrastructure development and shunting means of approach tracks, on the other – it will fix the shippers to the railroads and stop their outflow

Identification of CDC25 as a Common Therapeutic Target for Triple-Negative Breast Cancer

Directory of Open Access Journals (Sweden)

Jeff C. Liu

2018-04-01

Full Text Available Summary: CDK4/6 inhibitors are effective against cancer cells expressing the tumor suppressor RB1, but not RB1-deficient cells, posing the challenge of how to target RB1 loss. In triple-negative breast cancer (TNBC, RB1 and PTEN are frequently inactivated together with TP53. We performed kinome/phosphatase inhibitor screens on primary mouse Rb/p53-, Pten/p53-, and human RB1/PTEN/TP53-deficient TNBC cell lines and identified CDC25 phosphatase as a common target. Pharmacological or genetic inhibition of CDC25 suppressed growth of RB1-deficient TNBC cells that are resistant to combined CDK4/6 plus CDK2 inhibition. Minimal cooperation was observed in vitro between CDC25 antagonists and CDK1, CDK2, or CDK4/6 inhibitors, but strong synergy with WEE1 inhibition was apparent. In accordance with increased PI3K signaling following long-term CDC25 inhibition, CDC25 and PI3K inhibitors effectively synergized to suppress TNBC growth both in vitro and in xenotransplantation models. These results provide a rationale for the development of CDC25-based therapies for diverse RB1/PTEN/TP53-deficient and -proficient TNBCs. : Liu et al. report that inhibition of the protein phosphatase CDC25 kills diverse triple-negative breast cancer (TNBC cells. Moreover, CDC25 antagonists cooperate with other drugs, such as PI3K inhibitors, to efficiently suppress growth of human TNBC engrafted into mice. Keywords: triple negative breast cancer, basal-like breast cancer, therapy, RB1, PTEN, TP53, CDC25, WEE1, CHK1, checkpoint control

Rho Kinase (ROCK) collaborates with Pak to Regulate Actin Polymerization and Contraction in Airway Smooth Muscle.

Science.gov (United States)

Zhang, Wenwu; Bhetwal, Bhupal P; Gunst, Susan J

2018-05-10

The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation. We find that ROCK regulates airway smooth muscle contraction by activating the serine-threonine kinase Pak, which mediates the activation of Cdc42 and Neuronal-Wiskott-Aldrich Syndrome protein (N-WASp). N-WASP transmits signals from cdc42 to the Arp2/3 complex for the nucleation of actin filaments. These results demonstrate a novel molecular function for ROCK in the regulation of Pak and cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle. Rho kinase (ROCK), a RhoA GTPase effector, can regulate the contraction of airway and other smooth muscle tissues. In some tissues, ROCK can inhibit myosin regulatory light chain (RLC) phosphatase, which increases the phosphorylation of myosin RLC and promotes smooth muscle contraction. ROCK can also regulate cell motility and migration by affecting F-actin dynamics. Actin polymerization is stimulated by contractile agonists in airway smooth muscle tissues and is required for contractile tension development in addition to myosin RLC phosphorylation. We investigated the mechanisms by which ROCK regulates the contractility of tracheal smooth muscle tissues by expressing a kinase inactive mutant of ROCK, ROCK-K121G, in the tissues or by treating them with the ROCK inhibitor, H-1152P. Our results show no role for ROCK in the regulation of non-muscle or smooth muscle myosin RLC phosphorylation during contractile stimulation in this tissue

Sprouty regulates cell migration by inhibiting the activation of Rac1 GTPase

International Nuclear Information System (INIS)

Poppleton, Helen M.; Edwin, Francis; Jaggar, Laura; Ray, Ramesh; Johnson, Leonard R.; Patel, Tarun B.

2004-01-01

Sprouty (SPRY) protein negatively modulates fibroblast growth factor and epidermal growth factor actions. We showed that human SPRY2 inhibits cell growth and migration in response to serum and several growth factors. Using rat intestinal epithelial (IEC-6) cells, we investigated the involvement of the Rho family of GTPases, RhoA, Rac1, and cdc42 in SPRY2-mediated inhibition of cell migration and proliferation. The ability of TAT-tagged SPRY2 to inhibit proliferation and migration of IEC-6 cells transfected with constitutively active mutants of RhoA(G14V), Rac1(G12V), and cdc42 (F28L) was determined. Constitutively active RhoA(G14V), Rac1(G12V), or cdc42(F28L) did not protect cells from the anti-proliferative actions of TAT-SPRY2. The ability of TAT-hSPRY2 to inhibit migration was not altered by of RhoA(G14V) and cdc42(F28L). However, Rac1(G12V) obliterated the ability of SPRY2 to inhibit cell autonomous or serum-induced migration. Also, the activation of endogenous Rac1 was attenuated by TAT-SPRY2. Thus, SPRY2 mediates its anti-migratory actions by inhibiting Rac1 activation

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

Science.gov (United States)

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

14 CFR 221.61 - Rules and regulations governing foreign air transportation.

Science.gov (United States)

2010-01-01

... governing foreign air transportation. Instead of being included in the fares tariffs, the rules and regulations governing foreign air transportation required to be filed by §§ 221.20 and 221.30 and/or... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Rules and regulations governing foreign air...

Accuracy synthesis of T-shaped exit fixed mechanism in a double-crystal monochromator

International Nuclear Information System (INIS)

Wang Fengqin; Cao Chongzhen; Wang Jidai; Li Yushan; Gao Xueguan

2007-01-01

It is a key performance requirement for a double-crystal monochromator that the exit is fixed, and in order to improve the height accuracy of the exit in T-shaped exit fixed mechanism, the expression between the height of the exit and various original errors was put forward using geometrical analysis method. According to the independent action principle of original errors, accuracy synthesis of T-shaped exit fixed mechanism was studied by using the equal accuracy method, and the tolerance ranges of original errors were obtained. How to calculate the tolerance ranges of original errors was explained by giving an example. (authors)

Technological Progress, Exit and Trade

DEFF Research Database (Denmark)

Schröder, Philipp; Sørensen, Allan

productivity exporters are more likely to continue to export, and market exit is typically preceded by periods of contracting market shares. We show that the simple inclusion of exogenous economy wide technological progress into the standard Melitz (2003) model generates a tractable dynamic framework...

CDC 6600 Cordwood Module

CERN Multimedia

1964-01-01

The CDC 6600 cordwood module containing 64 silicon transistors. The module was mounted between two plates that were cooled conductive by a refrigeration unit via the front panel. The construction of this module uses the cord method, so called because the resistors seem to be stacked like cord between the two circuit boards in order to obtain a high density. The 6600 model contained nearly 6,000 such modules.

Do spouses coordinate their work exits? A combined survey and register analysis from Norway.

Science.gov (United States)

Syse, Astri; Solem, Per Erik; Ugreninov, Elisabeth; Mykletun, Reidar; Furunes, Trude

2014-09-01

Research on spouses' joint work exits is scarce, although household factors such as spouses' work status, marital quality, and caregiving burdens are likely to affect seniors' work engagement. We therefore examine whether the work exit probability of one spouse affects that of the other. Discrete-time hazard regression analyses of survey data linked to later registry information including all gainfully employed married respondents aged 50-74 with a working spouse (N = 1,764) were used to assess subsequent work exits. A spouse's work exit is a strong predictor of a respondent's work exit (hazard ratio 3.1, 95% confidence interval [2.5, 4.0]). Educational attainment, poor marital quality, and spouses' health and care needs do not predict work exits. Surprisingly, no gender differences are observed. Research on larger survey samples to distinguish different work exit routes and reasons for spouses' joint work exits appears warranted. To account for cultural and welfare state characteristics, cross-national studies ought to be undertaken. © The Author(s) 2013.

CDC Lab Values

Centers for Disease Control (CDC) Podcasts

2015-02-02

More than fifteen hundred scientists fill the lab benches at CDC, logging more than four million hours each year. CDC’s laboratories play a critical role in the agency’s ability to find, stop, and prevent disease outbreaks. This podcast provides a brief overview of what goes on inside CDC’s labs, and why this work makes a difference in American’s health.  Created: 2/2/2015 by Office of the Associate Director for Communication (OADC).   Date Released: 2/2/2015.

Experiment of cavitation erosion at the exit of a long orifice

Energy Technology Data Exchange (ETDEWEB)

Yagi, Yoshinori; Murase, Michio [Inst. of Nuclear Safety System Inc., Mihama, Fukui (Japan)

2002-09-01

We performed experiments to clarify mechanism of cavitation erosion and to predict cavitation erosion rate at the exit of a long orifice equipped at the chemical and volume control system in a pressurized water reactor (PWR). In order to find this mechanism, we used a high speed video camera. As the result, we observed bubble collapses near the exit of the orifice when flow condition was oscillating. So the bubble collapses due to the oscillation might cause the first stage erosion at the exit of the orifice. Using the orifice which had the cone-shaped exit, we observed that bubbles collapsed near the exit and then they collapsed at the upstream like a chain reaction. So this bubble collapse mechanism could be explained as follows: shock wave was generated by the bubble collapse near the exit, then it propagated upwards, consequently it caused the bubble collapse at the upstream. And we predicted erosion rate by evaluating the effect of the velocity and comparing the erosion resistance between the test speciment (aluminum) and the plant material (stainless steel) by means of vibratory tests. We compared the predicted erosion rate with that of the average value estimated from plant investigation, then we examined the applicability of these method to the plant evaluations. (author)

Have U.S. power plants become less technically efficient? The impact of carbon emission regulation

International Nuclear Information System (INIS)

Zhou, Yishu; Huang, Ling

2016-01-01

We estimate directional distance functions to measure the impact of carbon emission regulation, the Regional Greenhouse Gas Initiative (RGGI) in particular, on U.S. power plants' technical efficiency. The model shows that the average technical efficiency scores for coal and natural gas plants are 88.70% and 83.14% respectively, indicating a very technically efficient industry. We find no evidence of technical efficiency changes due to the RGGI regime in the RGGI area. In the same area, relatively less efficient coal plants exited the market and slightly more efficient natural gas plants entered, compared to the incumbent plants. In addition, some evidence of a spillover effect is found. Using a counterfactual analysis, the RGGI regulation leads to a 1.48% decline in the average technical efficiency for coal plants within neighboring states of RGGI during 2009–2013. - Highlights: • RGGI does not lead to a change in the technical efficiency of RGGI power plants. • Less efficient coal plants exit. • Entering natural gas plants are more efficient. • RGGI has a spillover effect on neighboring coal plants.

“Understanding exit from the founder’s business in family firms”

OpenAIRE

C. Salvato; F. Chirico; P. Sharma

2010-01-01

In this chapter we investigate the role of family-specific factors in facilitating or constraining business exit in family firms. Family business literature seems to have an implicit bias towards continuity and persistence in the founder’s business. This is explained by heavy emotional involvement and development of path-dependent core competences over generations. However, several long-lived family firms were able to successfully exit the founder’s business. Exit allowed them to free signifi...

Driver or passenger effects of augmented c-Myc and Cdc20 in gliomagenesis.

Science.gov (United States)

Ji, Ping; Zhou, Xinhui; Liu, Qun; Fuller, Gregory N; Phillips, Lynette M; Zhang, Wei

2016-04-26

Cdc20 and c-Myc are commonly overexpressed in a broad spectrum of cancers, including glioblastoma (GBM). Despite this clear association, whether c-Myc and Cdc20 overexpression is a driver or passenger event in gliomagenesis remains unclear. Both c-Myc and Cdc20 induced the proliferation of primary glial progenitor cells. c-Myc also promoted the formation of soft agar anchorage-independent colonies. In the RCAS/Ntv-a glia-specific transgenic mouse model, c-Myc increased the GBM incidence from 19.1% to 47.4% by 12 weeks of age when combined with kRas and Akt3 in Ntv-a INK4a-ARF (also known as CDKN2A)-null mice. In contrast, Cdc20 decreased the GBM incidence from 19.1% to 9.1%. Moreover, cell differentiation was modulated by c-Myc in kRas/Akt3-induced GBM on the basis of Nestin/GFAP expression (glial progenitor cell differentiation), while Cdc20 had no effect on primary glial progenitor cell differentiation. We used glial progenitor cells from Ntv-a newborn mice to evaluate the role of c-Myc and Cdc20 in the proliferation and transformation of GBM in vitro and in vivo. We further determined whether c-Myc and Cdc20 have a driver or passenger role in GBM development using kRas/Akt3 signals in a RCAS/Ntv-a mouse model. These results suggest that the driver or passenger of oncogene signaling is dependent on cellular status. c-Myc is a driver when combined with kRas/Akt3 oncogenic signals in gliomagenesis, whereas Cdc20 overexpression is a passenger. Inhibition of cell differentiation of c-Myc may be a target for anti-glioma therapy.

CDC Vital Signs-Preventing Stroke Deaths

Centers for Disease Control (CDC) Podcasts

This podcast is based on the September 2017 CDC Vital Signs report. Each year, more than 140,000 people die and many survivors face disability. Eighty percent of strokes are preventable. Learn the signs of stroke and how to prevent them.

Analytical and clinical performance of the CDC real time RT-PCR assay for detection and typing of dengue virus.

Science.gov (United States)

Santiago, Gilberto A; Vergne, Edgardo; Quiles, Yashira; Cosme, Joan; Vazquez, Jesus; Medina, Juan F; Medina, Freddy; Colón, Candimar; Margolis, Harold; Muñoz-Jordán, Jorge L

2013-01-01

Dengue is an acute illness caused by the positive-strand RNA dengue virus (DENV). There are four genetically distinct DENVs (DENV-1-4) that cause disease in tropical and subtropical countries. Most patients are viremic when they present with symptoms; therefore, RT-PCR has been increasingly used in dengue diagnosis. The CDC DENV-1-4 RT-PCR Assay has been developed as an in-vitro diagnostic platform and was recently approved by the US Food and Drug Administration (FDA) for detection of dengue in patients with signs or symptoms of mild or severe dengue. The primers and probes of this test have been designed to detect currently circulating strains of DENV-1-4 from around the world at comparable sensitivity. In a retrospective study with 102 dengue cases confirmed by IgM anti-DENV seroconversion in the convalescent sample, the RT-PCR Assay detected DENV RNA in 98.04% of the paired acute samples. Using sequencing as a positive indicator, the RT-PCR Assay had a 97.92% positive agreement in 86 suspected dengue patients with a single acute serum sample. After extensive validations, the RT-PCR Assay performance was highly reproducible when evaluated across three independent testing sites, did not produce false positive results for etiologic agents of other febrile illnesses, and was not affected by pathological levels of potentially interfering biomolecules. These results indicate that the CDC DENV-1-4 RT-PCR Assay provides a reliable diagnostic platform capable for confirming dengue in suspected cases.

Water-Exit Process Modeling and Added-Mass Calculation of the Submarine-Launched Missile

Directory of Open Access Journals (Sweden)

Yang Jian

2017-11-01

Full Text Available In the process that the submarine-launched missile exits the water, there is the complex fluid solid coupling phenomenon. Therefore, it is difficult to establish the accurate water-exit dynamic model. In the paper, according to the characteristics of the water-exit motion, based on the traditional method of added mass, considering the added mass changing rate, the water-exit dynamic model is established. And with help of the CFX fluid simulation software, a new calculation method of the added mass that is suit for submarine-launched missile is proposed, which can effectively solve the problem of fluid solid coupling in modeling process. Then by the new calculation method, the change law of the added mass in water-exit process of the missile is obtained. In simulated analysis, for the water-exit process of the missile, by comparing the results of the numerical simulation and the calculation of theoretical model, the effectiveness of the new added mass calculation method and the accuracy of the water-exit dynamic model that considers the added mass changing rate are verified.

RCAN1.4 regulates VEGFR-2 internalisation, cell polarity and migration in human microvascular endothelial cells.

Science.gov (United States)

Alghanem, Ahmad F; Wilkinson, Emma L; Emmett, Maxine S; Aljasir, Mohammad A; Holmes, Katherine; Rothermel, Beverley A; Simms, Victoria A; Heath, Victoria L; Cross, Michael J

2017-08-01

Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the calcineurin pathway in cells. It is expressed as two isoforms in vertebrates: RCAN1.1 is constitutively expressed in most tissues, whereas transcription of RCAN1.4 is induced by several stimuli that activate the calcineurin-NFAT pathway. RCAN1.4 is highly upregulated in response to VEGF in human endothelial cells in contrast to RCAN1.1 and is essential for efficient endothelial cell migration and tubular morphogenesis. Here, we show that RCAN1.4 has a role in the regulation of agonist-stimulated VEGFR-2 internalisation and establishment of endothelial cell polarity. siRNA-mediated gene silencing revealed that RCAN1 plays a vital role in regulating VEGF-mediated cytoskeletal reorganisation and directed cell migration and sprouting angiogenesis. Adenoviral-mediated overexpression of RCAN1.4 resulted in increased endothelial cell migration. Antisense-mediated morpholino silencing of the zebrafish RCAN1.4 orthologue revealed a disrupted vascular development further confirming a role for the RCAN1.4 isoform in regulating vascular endothelial cell physiology. Our data suggest that RCAN1.4 plays a novel role in regulating endothelial cell migration by establishing endothelial cell polarity in response to VEGF.

CDC STATE System Tobacco Legislation - Preemption Summary

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Preemption. The STATE...

Regulation of Kv1.4 potassium channels by PKC and AMPK kinases

DEFF Research Database (Denmark)

Andersen, Martin Nybo; Skibsbye, Lasse; Saljic, Arnela

2018-01-01

around the ubiquitin ligase Nedd4-2. In the present study we examined whether Kv1.4, constituting the cardiac Ito,s current, is subject to similar regulation. In the epithelial Madin-Darby Canine Kidney (MDCK) cell line, which constitutes a highly reproducible model system for addressing membrane...... targeting, we find, by confocal microscopy, that Kv1.4 cell surface expression is downregulated by activation of protein kinase C (PKC) and AMP-activated protein kinase (AMPK). In contrast, manipulating the activities of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serum and glucocorticoid......-regulated kinase 1 (SGK1) were without effect on channel localization. The PKC and AMPK-mediated downregulation of Kv1.4 membrane surface localization was confirmed by two-electrode voltage clamp in Xenopus laevis oocytes, where pharmacological activation of PKC and AMPK reduced Kv1.4 current levels. We further...

Collective behavior of mice passing through an exit under panic

Science.gov (United States)

Zhang, Teng; Zhang, Xuelin; Huang, Shenshi; Li, Changhai; Lu, Shouxiang

2018-04-01

Collective movement of animal in emergency condition has attracted growing attentions among researchers. However, many rules still need to be confirmed with adequate explanation. Study of collective behavior of mice can improve our understanding about the dynamics of pedestrian movement. However, its rules still need to be confirmed with adequate explanation. In this paper, collective behavior of mice passing through an exit under panic was investigated. The results showed that the total evacuation time decreased with exit width increasing in a certain range. Based on the different tendency of the curve in temporal evolution, the process of mice flow was divided into three stages. The density of mice near the exit peaks at a certain horizontal offset and starts to decrease over time. With the increase of the exit width, the duration of the higher density state decreased. We found that the frequency of time intervals obeyed a lognormal distribution or an exponential decay for different exit widths. In addition, the relationship between the group size and the group flow rate in different scenarios was analyzed. The phenomena found in our experiments show the collective behavioral characteristic of mice under panic. Our analysis in this paper will deepen our understanding of crowd dynamics in emergency condition.

CDC STATE System E-Cigarette Legislation - Licensure

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Licensure. The...

CDC STATE System E-Cigarette Legislation - Preemption

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Preemption. The...

CDC STATE System Tobacco Legislation - Youth Access

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Youth Access. The STATE...

CDC Vital Signs: Drinking and Driving

Science.gov (United States)

... Adapted from The ABCs of BAC, National Highway Traffic Safety Administration, 2005, and How to Control Your Drinking, WR Miller and RF Munoz, University of New Mexico, 1982. Self-reported annual drinking and driving episodes SOURCE: CDC Behavioral Risk Factor Surveillance System, ...

30 CFR 57.4530 - Exits for surface buildings and structures.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Exits for surface buildings and structures. 57... Fire Prevention and Control Installation/construction/maintenance § 57.4530 Exits for surface buildings and structures. Surface buildings or structures in which persons work shall have a sufficient number...

Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus Epichloë festucae have contrasting roles for ROS production and symbiotic infection synchronized with the host plant.

Science.gov (United States)

Kayano, Yuka; Tanaka, Aiko; Takemoto, Daigo

2018-01-01

Epichloë festucae is an endophytic fungus which systemically colonizes temperate grasses to establish symbiotic associations. Maintaining symptomless infection is a key requirement for endophytes, a feature that distinguishes them from pathogenic fungi. While pathogenic fungi extend their hyphae by tip growth, hyphae of E. festucae systemically colonize the intercellular space of expanding host leaves via a unique mechanism of hyphal intercalary growth. This study reports that two homologous Rho GTPases, Cdc42 and RacA, have distinctive roles in the regulation of E. festucae growth in planta. Here we highlight the vital role of Cdc42 for intercalary hyphal growth, as well as involvement of RacA in regulation of hyphal network formation, and demonstrate the consequences of mutations in these genes on plant tissue infection. Functions of Cdc42 and RacA are mediated via interactions with BemA and NoxR respectively, which are expected components of the ROS producing NOX complex. Symbiotic defects found in the racA mutant were rescued by introduction of a Cdc42 with key amino acids substitutions crucial for RacA function, highlighting the significance of the specific interactions of these GTPases with BemA and NoxR for their functional differentiation in symbiotic infection.

Exit, punishment and rewards in commons dilemmas: an experimental study.

Directory of Open Access Journals (Sweden)

Giangiacomo Bravo

Full Text Available Commons dilemmas are interaction situations where a common good is provided or exploited by a group of individuals so that optimal collective outcomes clash with private interests. Although in these situations, social norms and institutions exist that might help individuals to cooperate, little is known about the interaction effects between positive and negative incentives and exit options by individuals. We performed a modified public good game experiment to examine the effect of exit, rewards and punishment, as well as the interplay between exit and rewards and punishment. We found that punishment had a stronger effect than rewards on cooperation if considered by itself, whereas rewards had a stronger effect when combined with voluntary participation. This can be explained in terms of the 'framing effect', i.e., as the combination of exit and rewards might induce people to attach higher expected payoffs to cooperative strategies and expect better behaviour from others.

Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.

Science.gov (United States)

Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru

2017-07-14

Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.

Regulatory dephosphorylation of CDK at G₂/M in plants: yeast mitotic phosphatase cdc25 induces cytokinin-like effects in transgenic tobacco morphogenesis.

Science.gov (United States)

Lipavská, Helena; Masková, Petra; Vojvodová, Petra

2011-05-01

During the last three decades, the cell cycle and its control by cyclin-dependent kinases (CDKs) have been extensively studied in eukaryotes. This endeavour has produced an overall picture that basic mechanisms seem to be largely conserved among all eukaryotes. The intricate regulation of CDK activities includes, among others, CDK activation by CDC25 phosphatase at G₂/M. In plants, however, studies of this regulation have lagged behind as a plant Cdc25 homologue or other unrelated phosphatase active at G₂/M have not yet been identified. Failure to identify a plant mitotic CDK activatory phosphatase led to characterization of the effects of alien cdc25 gene expression in plants. Tobacco, expressing the Schizosaccharomyces pombe mitotic activator gene, Spcdc25, exhibited morphological, developmental and biochemical changes when compared with wild type (WT) and, importantly, increased CDK dephosphorylation at G₂/M. Besides changes in leaf shape, internode length and root development, in day-neutral tobacco there was dramatically earlier onset of flowering with a disturbed acropetal floral capacity gradient typical of WT. In vitro, de novo organ formation revealed substantially earlier and more abundant formation of shoot primordia on Spcdc25 tobacco stem segments grown on shoot-inducing media when compared with WT. Moreover, in contrast to WT, stem segments from transgenic plants formed shoots even without application of exogenous growth regulator. Spcdc25-expressing BY-2 cells exhibited a reduced mitotic cell size due to a shortening of the G₂ phase together with high activity of cyclin-dependent kinase, NtCDKB1, in early S-phase, S/G₂ and early M-phase. Spcdc25-expressing tobacco ('Samsun') cell suspension cultures showed a clustered, more circular, cell phenotype compared with chains of elongated WT cells, and increased content of starch and soluble sugars. Taken together, Spcdc25 expression had cytokinin-like effects on the characteristics studied

CDC WONDER: Online Tuberculosis Information System (OTIS)

Data.gov (United States)

U.S. Department of Health & Human Services — The Online Tuberculosis Information System (OTIS) on CDC WONDER contains information on verified tuberculosis (TB) cases reported to the Centers for Disease Control...

CDC STATE System E-Cigarette Legislation - Tax

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Tax. The STATE...

CDC Wonder Vaccine Adverse Event Reporting System

Data.gov (United States)

U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination,...

Critical heat flux and exit film flow rate in a flow boiling system

International Nuclear Information System (INIS)

Ueda, Tatsuhiro; Isayama, Yasushi

1981-01-01

The critical heat flux in a flowing boiling system is an important problem in the evaporating tubes with high thermal load such as nuclear reactors and boilers, and gives the practical design limit. When the heat flux in uniformly heated evaporating tubes is gradually raised, the tube exit quality increases, and soon, the critical heat flux condition arises, and the wall temperature near tube exit rises rapidly. In the region of low exit quality, the critical heat flux condition is caused by the transition from nucleating boiling, and in the region of high exit quality, it is caused by dry-out. But the demarcation of both regions is not clear. In this study, for the purpose of obtaining the knowledge concerning the critical heat flux condition in a flowing boiling system, the relation between the critical heat flux and exit liquid film flow rate was examined. For the experiment, a uniformly heated vertical tube supplying R 113 liquid was used, and the measurement in the range of higher heating flux and mass velocity than the experiment by Ueda and Kin was carried out. The experimental setup and experimental method, the critical heat flux and exit quality, the liquid film flow rate at heating zone exit, and the relation between the critical heat flux and the liquid film flow rate at exit are described. (Kako, I.)

Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2

Directory of Open Access Journals (Sweden)

Sanne H. Olesen

2015-01-01

Full Text Available The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein–protein interaction (PPI inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2 did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM, while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands.

First Degree Pacemaker Exit Block

Directory of Open Access Journals (Sweden)

Johnson Francis

2016-10-01

Full Text Available Usually atrial and ventricular depolarizations follow soon after the pacemaker stimulus (spike on the ECG. But there can be an exit block due to fibrosis at the electrode - tissue interface at the lead tip. This can increase the delay between the spike and atrial or ventricular depolarization.

Exit Planning At Joost El

DEFF Research Database (Denmark)

Nellemann, Camilla

2017-01-01

This is a Danish version. This case focuses on an owner-manager's considerations regarding his exit. Carsten Joost established Joost El in 2005. It currently employs 10 people. He has two sons but no intention to hand over the business to them. Rather, he hopes that his key employee eventually...

Implementation experiences of NASTRAN on CDC CYBER 74 SCOPE 3.4 operating system

Science.gov (United States)

Go, J. C.; Hill, R. G.

1973-01-01

The implementation of the NASTRAN system on the CDC CYBER 74 SCOPE 3.4 Operating System is described. The flexibility of the NASTRAN system made it possible to accomplish the change with no major problems. Various sizes of benchmark and test problems, ranging from two hours to less than one minute CP time were run on the CDC CYBER SCOPE 3.3, Univac EXEC-8, and CDC CYBER SCOPE 3.4. The NASTRAN installation deck is provided.

Effects of injection nozzle exit width on rotating detonation engine

Science.gov (United States)

Sun, Jian; Zhou, Jin; Liu, Shijie; Lin, Zhiyong; Cai, Jianhua

2017-11-01

A series of numerical simulations of RDE modeling real injection nozzles with different exit widths are performed in this paper. The effects of nozzle exit width on chamber inlet state, plenum flowfield and detonation propagation are analyzed. The results are compared with that using an ideal injection model. Although the ideal injection model is a good approximation method to model RDE inlet, the two-dimensional effects of real nozzles are ignored in the ideal injection model so that some complicated phenomena such as the reflected waves caused by the nozzle walls and the reversed flow into the nozzles can not be modeled accurately. Additionally, the ideal injection model overpredicts the block ratio. In all the cases that stabilize at one-wave mode, the block ratio increases as the nozzle exit width gets smaller. The dual-wave mode case also has a relatively high block ratio. A pressure oscillation in the plenum with the same main frequency with the rotating detonation wave is observed. A parameter σ is applied to describe the non-uniformity in the plenum. σ increases as the nozzle exit width gets larger. Under some condition, the heat release on the interface of fresh premixed gas layer and detonation products can be strong enough to induce a new detonation wave. A spontaneous mode-transition process is observed for the smallest exit width case. Due to the detonation products existing in the premixed gas layer before the detonation wave, the detonation wave will propagate through reactants and products alternately, and therefore its strength will vary with time, especially near the chamber inlet. This tendency gets weaker as the injection nozzle exit width increases.

CDC STATE System Tobacco Legislation - Smokefree Campus

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Campuses. The...

CDC STATE System Tobacco Legislation - Preemption Summary

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Preemption. The STATE...

CDC STATE System E-Cigarette Legislation - Preemption

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Preemption....

CDC STATE System E-Cigarette Legislation - Licensure

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Licensure....

Revisit the faster-is-slower effect for an exit at a corner

Science.gov (United States)

Chen, Jun Min; Lin, Peng; Wu, Fan Yu; Li Gao, Dong; Wang, Guo Yuan

2018-02-01

The faster-is-slower effect (FIS), which means that crowd at a high enough velocity could significantly increase the evacuation time to escape through an exit, is an interesting phenomenon in pedestrian dynamics. Such phenomenon had been studied widely and has been experimentally verified in different systems of discrete particles flowing through a centre exit. To experimentally validate this phenomenon by using people under high pressure is difficult due to ethical issues. A mouse, similar to a human, is a kind of self-driven and soft body creature with competitive behaviour under stressed conditions. Therefore, mice are used to escape through an exit at a corner. A number of repeated tests are conducted and the average escape time per mouse at different levels of stimulus are analysed. The escape times do not increase obviously with the level of stimulus for the corner exit, which is contrary to the experiment with the center exit. The experimental results show that the FIS effect is not necessary a universal law for any discrete system. The observation could help the design of buildings by relocating their exits to the corner in rooms to avoid the formation of FIS effect.

CDC WONDER: Mortality - Underlying Cause of Death

Data.gov (United States)

U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979. Data...

CDC STATE System Tobacco Legislation - Youth Access

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation—Youth Access. The STATE...

CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary Hyperparathyroidism

NARCIS (Netherlands)

van der Tuin, Karin; Tops, Carli M. J.; Adank, Muriel A.; Cobben, Jan-Maarten; Hamdy, Neveen A. T.; Jongmans, Marjolijn C.; Menko, Fred H.; van Nesselrooij, Bernadette P. M.; Netea-Maier, Romana T.; Oosterwijk, Jan C.; Valk, Gerlof D.; Wolffenbuttel, Bruce H. R.; Hes, Frederik J.; Morreau, Hans

2017-01-01

Context: Heterozygous pathogenic germline variants in CDC73 predispose to the development of primary hyperparathyroidism (pHPT) and, less frequently, ossifying fibroma of the jaw and renal and uterine tumors. Clinical information on CDC73-related disorders has so far been limited to small case

Application of an entry-exit tariff model to the gas transport system in Spain

International Nuclear Information System (INIS)

Alonso, Alejandro; Serrano, Miguel; Olmos, Luis

2010-01-01

Under an entry-exit gas tariff system, reservation of capacity is split into entry capacity, to transport gas from the injection points to a virtual balancing point, and exit capacity, to transport gas from the balancing point to the exit points in the system. Entry-exit tariff for gas transport systems have been recommended by the 3rd EU Energy Package, since they are cost reflective, facilitate gas trade and can provide signals for the location of gas injections or off-takes. The advisability of applying an entry-exit tariff system is discussed in this paper. Apart from this, authors propose an entry-exit tariff model and apply it to compute charges for the Spanish gas transport system in 2009. Results produced by the model are presented as coefficients which should multiply the current postal transport tariff. The paper concludes that entry-exit tariffs would be useful location signals which would result in a better use of the gas transport system in Spain. In those cases where demand exceeds available capacity, as it occurs at the congested connection with France, entry-exit tariffs could be supplemented by capacity charges at entry points resulting from auctions. (author)

"Know More Hepatitis:" CDC's National Education Campaign to Increase Hepatitis C Testing Among People Born Between 1945 and 1965.

Science.gov (United States)

Jorgensen, Cynthia; Carnes, C Amanda; Downs, Alycia

2016-01-01

In 2012, CDC issued recommendations calling for those born between 1945 and 1965, or baby boomers, to get tested for the hepatitis C virus. To help implement this recommendation, CDC developed "Know More Hepatitis," a multimedia national education campaign. Guided by behavioral science theories and formative research, the campaign used multiple strategies to reach baby boomers and health-care providers with messages encouraging baby boomers to get tested for hepatitis C. With a limited campaign budget, the "Know More Hepatitis" campaign relied mostly on donated time and space from broadcast and print outlets. Donated placements totaled approximately $14.7 million, which reflected a more than 12-to-1 return on the campaign investment. This effort was supplemented with a small, paid digital advertising campaign. Combining audience impressions from both paid and donated campaign efforts resulted in more than 1.2 billion audience impressions.

The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas

Science.gov (United States)

Wang, Zhihui; Tropè, Claes G; Suo, Zhenhe; Trøen, Gunhild; Yang, Guanrui; Nesland, Jahn M; Holm, Ruth

2008-01-01

Background 14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown. Methods We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome. Results In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p = 0.001, p = 0.002 and p = 0.001, respectively) and deep invasion (p = 0.01, p = 0.001 and p = 0.007, respectively). Variations of 14-3-3σ protein expression were not associated to disease-specific survival. Conclusion Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis. PMID:18950492

The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas

Directory of Open Access Journals (Sweden)

Suo Zhenhe

2008-10-01

Full Text Available Abstract Background 14-3-3 sigma (σ promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown. Methods We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome. Results In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p = 0.001, p = 0.002 and p = 0.001, respectively and deep invasion (p = 0.01, p = 0.001 and p = 0.007, respectively. Variations of 14-3-3σ protein expression were not associated to disease-specific survival. Conclusion Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis.

The use of the exit interview to reduce turnover amongst healthcare professionals.

Science.gov (United States)

Flint, Anndrea; Webster, Joan

2011-01-19

Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. We used a comprehensive search strategy including an electronic search of the following databases: DARE, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC (search date: 7 September 2010) and EPOC Specialised Register (search date: 30 September 2009). We also screened the reference lists of included studies and relevant reviews. Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. Two review authors independently assessed trial quality and extracted data. The search identified 1560 citations of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment. They were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no trials that matched our inclusion criteria. Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover.

CDC Vital Signs-Cancer and Obesity

Centers for Disease Control (CDC) Podcasts

This podcast is based on the October 2017 CDC Vital Signs report. Obesity is a leading cancer risk factor. Unfortunately, two out of three U.S. adults weigh more than recommended. Find out what can be done to help people get to and keep a healthy weight.

C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity.

Science.gov (United States)

Chalat, Madhavan; Moleschi, Kody; Molday, Robert S

2017-02-01

ATP8A2 is a P4-ATPase that flips phosphatidylserine and phosphatidylethanolamine across cell membranes. This generates membrane phospholipid asymmetry, a property important in many cellular processes, including vesicle trafficking. ATP8A2 deficiency causes severe neurodegenerative diseases. We investigated the role of the C-terminus of ATP8A2 in its expression, subcellular localization, interaction with its subunit CDC50A, and function as a phosphatidylserine flippase. C-terminal deletion mutants exhibited a reduced tendency to solubilize in mild detergent and exit the endoplasmic reticulum. The solubilized protein, however, assembled with CDC50A and displayed phosphatidylserine flippase activity. Deletion of the C-terminal 33 residues resulted in reduced phosphatidylserine-dependent ATPase activity, phosphatidylserine flippase activity, and neurite extension in PC12 cells. These reduced activities were reversed with 60- and 80-residue C-terminal deletions. Unlike the yeast P4-ATPase Drs2, ATP8A2 is not regulated by phosphoinositides but undergoes phosphorylation on the serine residue within a CaMKII target motif. We propose a model in which the C-terminus of ATP8A2 consists of an autoinhibitor domain upstream of the C-terminal 33 residues and an anti-autoinhibitor domain at the extreme C-terminus. The latter blocks the inhibitory activity of the autoinhibitor domain. We conclude that the C-terminus plays an important role in the efficient folding and regulation of ATP8A2. © 2017 Chalat et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Exploring the Relationship of Exit Flow and Jam Density in Panic Scenarios Using Animal Dynamics

NARCIS (Netherlands)

Sobhani, A.; Sarvi, M.; Duives, D.C.; Ejtemai, O.; Aghabayk, K.; Hoogendoorn, S.P.

2014-01-01

There are few studies investigating crowd dynamics in panic situations. They used measures such as exit flow rate to explore the exit performance in evacuation scenarios. However, there is limited research exploring the relationship of exit flow rate and density behind the exit for panic scenarios.

CDC WONDER: Sexually Transmitted Disease (STD) morbidity

Data.gov (United States)

U.S. Department of Health & Human Services — The Sexually Transmitted Disease (STD) Morbidity online databases on CDC WONDER contain case reports reported from the 50 United States and D.C., Puerto Rico, Virgin...

CDC WONDER: Sexually Transmitted Disease (STD) Morbidity

Data.gov (United States)

U.S. Department of Health & Human Services — The Sexually Transmitted Disease (STD) Morbidity online databases on CDC WONDER contain case reports reported from the 50 United States and D.C., Puerto Rico, Virgin...

CDC Study Finds Fecal Contamination in Pools

Science.gov (United States)

... Communication (404) 639-3286 CDC study finds fecal contamination in pools A study of public pools done ... The E. coli is a marker for fecal contamination. Finding a high percentage of E. coli-positive ...

CDC WONDER: Mortality - Multiple Cause of Death

Data.gov (United States)

U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2006. These data are...

CDC WONDER: Mortality - Multiple Cause of Death

Data.gov (United States)

U.S. Department of Health & Human Services — The Mortality - Multiple Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are based on...

CDC Vital Signs: Making Health Care Safer

Science.gov (United States)

... of Page What Can Be Done The Federal government is Implementing activities across all government agencies to ... Making Health Care Safer [PSA – 0:60 seconds] Digital Press Kit: CDC Modeling Predicts Growth of Drug- ...

The transcription factor bZIP14 regulates the TCA cycle in the diatom Phaeodactylum tricornutum.

Science.gov (United States)

Matthijs, Michiel; Fabris, Michele; Obata, Toshihiro; Foubert, Imogen; Franco-Zorrilla, José Manuel; Solano, Roberto; Fernie, Alisdair R; Vyverman, Wim; Goossens, Alain

2017-06-01

Diatoms are amongst the most important marine microalgae in terms of biomass, but little is known concerning the molecular mechanisms that regulate their versatile metabolism. Here, the pennate diatom Phaeodactylum tricornutum was studied at the metabolite and transcriptome level during nitrogen starvation and following imposition of three other stresses that impede growth. The coordinated upregulation of the tricarboxylic acid (TCA) cycle during the nitrogen stress response was the most striking observation. Through co-expression analysis and DNA binding assays, the transcription factor bZIP14 was identified as a regulator of the TCA cycle, also beyond the nitrogen starvation response, namely in diurnal regulation. Accordingly, metabolic and transcriptional shifts were observed upon overexpression of bZIP14 in transformed P. tricornutum cells. Our data indicate that the TCA cycle is a tightly regulated and important hub for carbon reallocation in the diatom cell during nutrient starvation and that bZIP14 is a conserved regulator of this cycle. © 2017 The Authors.

CDC Vital Signs-African American Health

Centers for Disease Control (CDC) Podcasts

This podcast is based on the May 2017 CDC Vital Signs report. The life expectancy of African Americans has improved, but it's still an average of four years less than whites. Learn what can be done so all Americans can have the opportunity to pursue a healthy lifestyle.

International Competition and Small-Firm Exit in US Manufacturing

OpenAIRE

Robert M Feinberg

2013-01-01

This study analyzes both the determinants of small firm exit rates in US manufacturing over the 1989–2004 period, especially the reaction of domestic firms to the nature of foreign competition as measured by industry-specific real exchange rate movements (interacted with import penetration by industry). These international pressures seem to lead to increased rates of smallest-firm exit in manufacturing, though the magnitudes of these effects are smaller than sometimes discussed. However, high...

CDC Vital Signs-Hospital Actions Affect Breastfeeding

Centers for Disease Control (CDC) Podcasts

This podcast is based on the October 2015 CDC Vital Signs report. Hospitals can implement the Ten Steps to Successful Breastfeeding to be designated as "Baby-Friendly" and support more moms in a decision to breastfeed.

Exiting RCRA Subtitle C regulation data for supporting a new regulatory path for immobilized mixed debris

Energy Technology Data Exchange (ETDEWEB)

Porter, C.L. [Jetseal, Inc., Idaho Falls, ID (United States); Carson, S.D.; Cheng, Wu-Ching [Sandia National Labs., Albuquerque, NM (United States)

1995-12-31

This paper presents analytical and empirical data that provide technical support for the position that mixed debris (debris contaminated with both radioactive and hazardous constituents) treated by immobilization in accordance with 40 CFR 268.45 can exit RCRA Subtitle C requirements at the time the treatment is complete. Pathways analyses and risk assessments of low-level waste and RCRA mixed waste disposal facilities show that these two types of facilities provide equivalent long-term (> 100 years) performance and protection of human health and the environment. A proposed two-tier approach for waste form performance criteria is discussed.

Analytical and clinical performance of the CDC real time RT-PCR assay for detection and typing of dengue virus.

Directory of Open Access Journals (Sweden)

Gilberto A Santiago

Full Text Available Dengue is an acute illness caused by the positive-strand RNA dengue virus (DENV. There are four genetically distinct DENVs (DENV-1-4 that cause disease in tropical and subtropical countries. Most patients are viremic when they present with symptoms; therefore, RT-PCR has been increasingly used in dengue diagnosis. The CDC DENV-1-4 RT-PCR Assay has been developed as an in-vitro diagnostic platform and was recently approved by the US Food and Drug Administration (FDA for detection of dengue in patients with signs or symptoms of mild or severe dengue. The primers and probes of this test have been designed to detect currently circulating strains of DENV-1-4 from around the world at comparable sensitivity. In a retrospective study with 102 dengue cases confirmed by IgM anti-DENV seroconversion in the convalescent sample, the RT-PCR Assay detected DENV RNA in 98.04% of the paired acute samples. Using sequencing as a positive indicator, the RT-PCR Assay had a 97.92% positive agreement in 86 suspected dengue patients with a single acute serum sample. After extensive validations, the RT-PCR Assay performance was highly reproducible when evaluated across three independent testing sites, did not produce false positive results for etiologic agents of other febrile illnesses, and was not affected by pathological levels of potentially interfering biomolecules. These results indicate that the CDC DENV-1-4 RT-PCR Assay provides a reliable diagnostic platform capable for confirming dengue in suspected cases.

Improved social force model based on exit selection for microscopic pedestrian simulation in subway station

Institute of Scientific and Technical Information of China (English)

郑勋; 李海鹰; 孟令云; 许心越; 陈旭

2015-01-01

An improved social force model based on exit selection is proposed to simulate pedestrians’ microscopic behaviors in subway station. The modification lies in considering three factors of spatial distance, occupant density and exit width. In addition, the problem of pedestrians selecting exit frequently is solved as follows: not changing to other exits in the affected area of one exit, using the probability of remaining preceding exit and invoking function of exit selection after several simulation steps. Pedestrians in subway station have some special characteristics, such as explicit destinations, different familiarities with subway station. Finally, Beijing Zoo Subway Station is taken as an example and the feasibility of the model results is verified through the comparison of the actual data and simulation data. The simulation results show that the improved model can depict the microscopic behaviors of pedestrians in subway station.

[Prokaryotic expression and histological localization of the Taenia solium CDC37 gene].

Science.gov (United States)

Huang, Jiang; Li, Bo; Dai, Jia-Lin; Zhang, Ai-Hua

2013-02-01

To express Taenia solium gene encoding cell division cycle 37 protein (TsCDC37) and investigate its antigenicity and localization in adults of Taenia solium. The complete coding sequence of TsCDC37 was amplified by PCR based on the recombinant plasmid clone from the cDNA library of adult Taenia solium. The PCR product was cloned into a prokaryotic expression vector pET-28a (+). The recombinant expression plasmid was identified by PCR, double endonuclease digestion and sequencing. The recombinant plasmid was transformed into E. coli BL21/DE3 and followed by expression of the protein induced by IPTG. The mice were immunized subcutaneously with purified recombinant TsCDC37 formulated in Freund's adjuvant. The antigenicity of the recombinant protein was examined by Western blotting. The localization of TsCDC37 in adult worms was demonstrated by immunofluorescent technique. The recombinant expression vector was constructed successfully. The recombinant protein was about M(r) 52 000, it was then purified and specifically recognized by immuno sera of SD rats and sera from patients infected with Taenia solium, Taenia saginata or Taenia asiatica. The immunofluorescence assay revealed that TsCDC37 located at the tegument of T. solium adult and the eggs. TsCDC37 gene has been expressed with immunoreactivity. The recombinant protein is mainly expressed in tegument and egg, and is a common antigen of the three human taenia cestodes.

CDC Vital Signs-Heroin Epidemic

Centers for Disease Control (CDC) Podcasts

2015-07-07

This podcast is based on the July 2015 CDC Vital Signs report. Heroin use and heroin-related overdose deaths are increasing. Most people are using it with other drugs, especially prescription opioid painkillers. Learn what can be done to prevent and treat the problem.  Created: 7/7/2015 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 7/7/2015.

Does Business Cycle Have an Impact on Entrants and Exits?

Directory of Open Access Journals (Sweden)

Nikolay Sterev

2017-03-01

Full Text Available Purpose: The role of entrants and exits has enlarged indisputably over recent years. The basic explanation is connected to the deepening of innovation's influence on industrial growth. Furthermore, new businesses have to be more effective, and based on products, technological or organizational innovations, and exits have to be ineffective (respectively unprofitable, based on denoted products or technology. Design/methodology/approach: According to the above-mentioned prerequisites, policymakers need to manage the role (respectively the impact that entrants (new start-up companies and exits play in industrial growth. Nevertheless, this impact is not a cornerstone of the Bulgarian National Strategy, or the Europe 2020 Strategy. Findings: The paper tries to answer the following two questions: 1 Do new start-up companies and exits have any role and influence on economic growth in Bulgaria? and 2 Does the role (respectively the impact of entrants and exits in industrial growth change according to economic cycle? Research limitations/implications: In addition, according to the Lisbon Strategy, as well as the European Union's (EU Strategy 2020, the current economic policy supports entrepreneurship and innovations. Thus, the establishment of innovative companies, as well as the development of innovative, incumbent business are core issues of EU economic policy for the past decade. Originality/value: The paper builds on the industrial dynamic methodology and on the understanding of how business decisions (entrepreneurship, innovations, and R&D on micro level correspond to macro level (GDP growth and innovation policy.

Frequent alterations of SLIT2–ROBO1–CDC42 signalling pathway ...

Indian Academy of Sciences (India)

breast cancer; alterations of SLIT2–ROBO1 signalling; active CDC42; ... proportion of four subtypes were tested for molecular alterations of SLIT2, ... reduced expression of phospho Serine-71 CDC42 predicted poor survival of BC patients.

The comparison of exit-site care with normal saline and povidone-iodine in preventing exit-site infection and peritonitis in children on chronic peritoneal dialysis treatment

Directory of Open Access Journals (Sweden)

Onder Yavascan

2011-01-01

Full Text Available Peritonitis and catheter exit- site infections (ESI are important causes of hospitalization and catheter loss in patients undergoing chronic peritoneal dialysis (CPD. The frequency of infection can be reduced by scrupulous exit- site care with or without topical antiseptics. There are no studies showing any benefit in the use of povidone-iodine or normal saline for care of exit- sites in long- term CPD patients. In this study, we aimed to determine the potential effectiveness of the application of povidone-iodine or normal saline at the catheter exit- site in preventing ESI and peritonitis in children on CPD. A total of 98 patients treated with either povidone-iodine or normal saline were included in this study. Group I (34 patients used povidone-iodine and group II (64 patients simply cleansed the exit- site with normal saline (0.9% NaCl. Dressings were changed 2 to 3 times in a week. The total cumulative follow- up time was 3233 patient- months. ESIs occurred in 10 (29.4% of 34 patients using povidone-iodine and in 10 (15.6% of 64 patients using normal saline. The frequency of ESI was significantly high in group I (povidone-iodine patients. The mean rate of ESI was 1 episode/60.8 patient- months for group I versus 1 episode/144 patient- months for group II (P 0.05. In conclusion, exit- site care with normal saline is an effective strategy in reducing the incidence of ESI in children on CPD. It can thus significantly reduce morbidity, catheter loss, and the need to transfer patients on peritoneal dialysis to hemodialysis.

CDC-reported assisted reproductive technology live-birth rates may mislead the public.

Science.gov (United States)

Kushnir, Vitaly A; Choi, Jennifer; Darmon, Sarah K; Albertini, David F; Barad, David H; Gleicher, Norbert

2017-08-01

The Centre for Disease Control and Prevention (CDC) publicly reports assisted reproductive technology live-birth rates (LBR) for each US fertility clinic under legal mandate. The 2014 CDC report excluded 35,406 of 184,527 (19.2%) autologous assisted reproductive technology cycles that involved embryo or oocyte banking from LBR calculations. This study calculated 2014 total clinic LBR for all patients utilizing autologous oocytes two ways: including all initiated assisted reproductive technology cycles or excluding banking cycles, as done by the CDC. The main limitation of this analysis is the CDC report did not differentiate between cycles involving long-term banking of embryos or oocytes for fertility preservation from cycles involving short-term embryo banking. Twenty-seven of 458 (6%) clinics reported over 40% of autologous cycles involved banking, collectively performing 12% of all US assisted reproductive technology cycles. LBR in these outlier clinics calculated by the CDC method, was higher than the other 94% of clinics (33.1% versus 31.1%). However, recalculated LBR including banking cycles in the outlier clinics was lower than the other 94% of clinics (15.5% versus 26.6%). LBR calculated by the two methods increasingly diverged based on proportion of banking cycles performed by each clinic reaching 4.5-fold, thereby, potentially misleading the public. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Influence of drill helical direction on exit damage development in drilling carbon fiber reinforced plastic

Science.gov (United States)

Bai, Y.; Jia, Z. Y.; Wang, F. J.; Fu, R.; Guo, H. B.; Cheng, D.; Zhang, B. Y.

2017-06-01

Drilling is inevitable for CFRP components’ assembling process in the aviation industry. The exit damage frequently occurs and affects the load carrying capacity of components. Consequently, it is of great urgency to enhance drilling exit quality on CFRP components. The article aims to guide the reasonable choice of drill helical direction and effectively reduce exit damage. Exit observation experiments are carried out with left-hand helical, right-hand helical and straight one-shot drill drilling T800S CFRP laminates separately. The development rules of exit damage and delamination factor curves are obtained. Combined with loading conditions and fracture modes of push-out burrs, and thrust force curves, the influence of drill helical direction on exit damage development is derived. It is found that the main fracture modes for left-hand helical, right-hand helical, and straight one-shot drill are mode I, extrusive fracture, mode III respectively. Among them, mode III has the least effect on exit damage development. Meanwhile, the changing rate of thrust force is relative slow for right-hand helical and straight one-shot drill in the thrust force increasing phase of stage II, which is disadvantaged for exit damage development. Therefore, straight one-shot drill’s exit quality is the best.

CDC Vital Signs–Legionnaires’ Disease

Centers for Disease Control (CDC) Podcasts

2017-06-06

This podcast is based on the June 2017 CDC Vital Signs report. Legionnaires’ disease is a serious, often deadly lung infection. People most commonly get it by breathing in water droplets containing Legionella germs. Learn how to prevent infections from Legionella.  Created: 6/6/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 6/6/2017.

CDC Vital Signs-Communication Can Save Lives

Centers for Disease Control (CDC) Podcasts

This podcast is based on the August 2015 CDC Vital Signs report. Antibiotic-resistant germs cause at least 23,000 deaths each year. Learn how public health authorities and health care facilities can work together to save lives.

Variation of the cold intermediate water in the Black Sea exit of the Strait of Istanbul (Bosphorus and its transfer through the strait

Directory of Open Access Journals (Sweden)

Huseyin Yuce

2012-04-01

Full Text Available The cold intermediate water (CIW, T < 8°C entering the Strait of Istanbul and its variation along the strait have been studied by using monthly conductivity-temperature-depth (CTDdata sets collected during the period from 1996 to 2000. In the northern exit of the strait, CIW is located between the seasonal thermocline and Mediterranean water originating from the lowerlayer of the Sea of Marmara. The thickness of CIW decreases fromApril to October. In the Strait of Istanbul, CIW is observedas a layer of temperature < 14$^{circ}$C. The thickness of thismodified cold intermediate water flowing southwards with the upper layer decreases, while its temperature increases along thestrait due to mixing with adjacent water. In the southern exit of the strait, the modified cold intermediate water is observed during the period from May to October. If CIW exists in the Black Sea exit region of the strait, modified cold water is found inthe Marmara exit region during the same period. The distribution of CIW in the Strait of Istanbul contributes to our understanding of the dynamics of the strait, especially in the summer months.

Suppressor Analysis of CRL4Cdt2 Defective and cdc48-353 Temperature Sensitive Mutants in Fission Yeast

DEFF Research Database (Denmark)

Marinova, Irina Nikolaeva

chaperone-like complex involved in numerous cellular processes, including protein degradation, cell cycle control, DNA repair, and vesicle fusion. The cdc48 gene is essential in fission yeast and mutations or changes in Cdc48/p97 protein expression have been linked to neurological disorders and cancer......SummaryPart 1CRL4Cdt2 E3 ligase is a key regulator of cellular proliferation and genome integrity, as it promotes the degradation of proteins involved in cell cycle progression, DNA replication and repair. In fission yeast the small intrinsically disordered protein Spd1 is targeted for degradation...... that these mutations alleviate the checkpoint dependency, the DNA damage sensitivity and the meiotic defects associated with Spd1 accumulation. Further analysis showed that whereas the V40G and S43L substitutions do not have a significant impact on Suc22R2 nuclear import function of Spd1, they affect the interaction...

Informe Signos Vitales de los CDC Obesidad infantil - (Childhood Obesity)

Centers for Disease Control (CDC) Podcasts

2013-08-06

Este podcast se basa en el informe Signos Vitales de los CDC de agosto del 2013. La tasa de obesidad entre los niños en edad prescolar de bajos ingresos ha disminuido, pero todavía uno de cada seis niños hispanos es obeso. Este programa habla brevemente sobre lo que se puede hacer.  Created: 8/6/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/6/2013.

CDC 24/7: Saving Lives, Protecting People

Centers for Disease Control (CDC) Podcasts

2012-06-04

24/7, CDC provides health information, responds to public health emergencies and natural disasters, and monitors disease.  Created: 6/4/2012 by Office of the Associate Director of Communciation (OADC).   Date Released: 6/4/2012.

Does the CDC Definition of Fever Accurately Predict Inflammation and Infection in Persons With SCI?

Science.gov (United States)

Trbovich, Michelle; Li, Carol; Lee, Shuko

2016-01-01

Background: Pneumonia and septicemia have the greatest impact on reduced life expectancy in persons with spinal cord injury (SCI). Fever is often the first presenting symptom of infection or inflammation. Thermoregulatory dysfunction in persons with SCI may preclude a typical febrile response to infection or inflammation and thus delay diagnostic workup. Objective: To determine the core temperature of persons with SCI in the setting of infection or inflammation and the frequency with which it meets criteria for the CDC definition of fever (>100.4°F). Methods: Retrospective review of hospitalized SCI patients over 5 years with a diagnosis of infection or inflammation (DI), defined by serum leukocytosis. In this study, 458 persons with paraplegia (PP) and 483 persons with tetraplegia (TP) had 4,191 DI episodes. Aural temperatures (T au ) on the day of DI, 7 days prior, and 14 days afterwards were abstracted from medical records. Main outcome measures were average T au at DI, frequency of temperatures >100.4°F at DI, and average baseline temperatures before and after DI. Results: Average T au at DI was 98.2°F (±1.5) and 98.2°F (±1.4) in the TP and PP groups, respectively, with only 11.6% to 14% of DI resulting in T au >100.4°F. Baseline temperatures ranged from 97.9°F (±0.7) to 98.0°F (±0.8). Conclusion: SCI persons with leukocytosis infrequently mount a fever as defined by the CDC, and baseline temperatures were subnormal (100.4°F is not a sensitive predictor of infection or inflammation in persons with SCI. Clinicians should be vigilant for alternative symptoms of infection and inflammation in these patients, so diagnostic workup is not delayed.

Frequent alterations of SLIT2–ROBO1–CDC42 signalling pathway ...

Indian Academy of Sciences (India)

2016-09-07

Sep 7, 2016 ... Keywords. breast cancer; alterations of SLIT2–ROBO1 signalling; active CDC42; pSer71-CDC42 . Journal of ... have already been studied in head and neck squamous cell ...... lung, oral, cervical, breast, kidney (Dallol et al.

Epigenetics as a First Exit Problem

Science.gov (United States)

Aurell, E.; Sneppen, K.

2002-01-01

We develop a framework to discuss the stability of epigenetic states as first exit problems in dynamical systems with noise. We consider in particular the stability of the lysogenic state of the λ prophage. The formalism defines a quantitative measure of robustness of inherited states.

CDC Vital Signs–Opioid Overdoses Treated in Emergency Departments

Centers for Disease Control (CDC) Podcasts

2018-03-06

This podcast is based on the March 2018 CDC Vital Signs report. Opioid overdoses continue to increase in the United States. Learn what can be done to help prevent opioid overdose and death.  Created: 3/6/2018 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/6/2018.

Cdc14 phosphatase

DEFF Research Database (Denmark)

Machín, Félix; Quevedo Rodriguez, Oliver; Ramos-Pérez, Cristina

2016-01-01

and cancer cells uncontrollably divide, much attention has been put into knocking down CDK activity. However, much less is known on the consequences of interfering with the phosphatases that put an end to the cell cycle. We have addressed in recent years the consequences of transiently inactivating the only...

Evaluation of six TPS algorithms in computing entrance and exit doses

Science.gov (United States)

Metwaly, Mohamed; Glegg, Martin; Baggarley, Shaun P.; Elliott, Alex

2014-01-01

Entrance and exit doses are commonly measured in in vivo dosimetry for comparison with expected values, usually generated by the treatment planning system (TPS), to verify accuracy of treatment delivery. This report aims to evaluate the accuracy of six TPS algorithms in computing entrance and exit doses for a 6 MV beam. The algorithms tested were: pencil beam convolution (Eclipse PBC), analytical anisotropic algorithm (Eclipse AAA), AcurosXB (Eclipse AXB), FFT convolution (XiO Convolution), multigrid superposition (XiO Superposition), and Monte Carlo photon (Monaco MC). Measurements with ionization chamber (IC) and diode detector in water phantoms were used as a reference. Comparisons were done in terms of central axis point dose, 1D relative profiles, and 2D absolute gamma analysis. Entrance doses computed by all TPS algorithms agreed to within 2% of the measured values. Exit doses computed by XiO Convolution, XiO Superposition, Eclipse AXB, and Monaco MC agreed with the IC measured doses to within 2%‐3%. Meanwhile, Eclipse PBC and Eclipse AAA computed exit doses were higher than the IC measured doses by up to 5.3% and 4.8%, respectively. Both algorithms assume that full backscatter exists even at the exit level, leading to an overestimation of exit doses. Despite good agreements at the central axis for Eclipse AXB and Monaco MC, 1D relative comparisons showed profiles mismatched at depths beyond 11.5 cm. Overall, the 2D absolute gamma (3%/3 mm) pass rates were better for Monaco MC, while Eclipse AXB failed mostly at the outer 20% of the field area. The findings of this study serve as a useful baseline for the implementation of entrance and exit in vivo dosimetry in clinical departments utilizing any of these six common TPS algorithms for reference comparison. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.N‐, 87.53.Bn PMID:24892349

After exit: Academic achievement patterns of former English language learners.

Directory of Open Access Journals (Sweden)

Ester J. de Jong

2004-09-01

Full Text Available With few exceptions, accountability systems for programs for English language learners (ELLs have focused on the achievement patterns of ELLs who are still considered “limited English proficient” and program evaluations have been unable to answer the question whether ELLs actually catch up with English proficient peers after attending a bilingual or English as a Second Language (ESL program. Disaggregating data for former ELLs can therefore provide important information for long-term district and program accountability. The study was concerned with the achievement patterns in English language arts, Math, and Science of former ELLs who attended a bilingual and a English as a Second Language (ESL program. It also explored whether length of program participation and grade level exited played a significant role in predicting academic achievement patterns for these exited students. Results indicate that 4th grade students more closely paralleled non- ELL students’ achievement patterns than 8th grade students, particularly for the BE students. While length of program participation is not a significant predictor of former ELLs’ academic success, exit grade does emerge as an important variable to take into consideration in setting exit guidelines.

CDC Vital Signs-Heart Age

Centers for Disease Control (CDC) Podcasts

This podcast is based on the September 2015 CDC Vital Signs report. Your heart age is the age of your heart and blood vessels as a result of your risk factors for heart attack and stroke. If you smoke or have high blood pressure, your heart age will be much higher than your actual age. Learn what you can do to lower your heart age and keep it low.

CDC Vital Signs-Hispanic Health

Centers for Disease Control (CDC) Podcasts

This podcast is based on the May 2015 CDC Vital Signs report. About one in six people living in the U.S. are Hispanic. The two leading causes of death in this group are heart disease and cancer, accounting for two out of five deaths. Unfortunately, many Hispanics face considerable barriers to getting high quality health care, including language and low income. Learn what can be done to reduce the barriers.

Structure and function of the AAA+ ATPase p97/Cdc48p.

Science.gov (United States)

Xia, Di; Tang, Wai Kwan; Ye, Yihong

2016-05-25

p97 (also known as valosin-containing protein (VCP) in mammals or Cdc48p in Saccharomyces cerevisiae) is an evolutionarily conserved ATPase present in all eukaryotes and archaebacteria. In conjunction with a collection of cofactors and adaptors, p97/Cdc48p performs an array of biological functions mostly through modulating the stability of 'client' proteins. Using energy from ATP hydrolysis, p97/Cdc48p segregates these molecules from immobile cellular structures such as protein assemblies, membrane organelles, and chromatin. Consequently, the released polypeptides can be efficiently degraded by the ubiquitin proteasome system or recycled. This review summarizes our current understanding of the structure and function of this essential cellular chaperoning system. Published by Elsevier B.V.

Articles Published and Downloaded by Public Health Scientists: Analysis of Data From the CDC Public Health Library, 2011-2013.

Science.gov (United States)

Iskander, John; Bang, Gail; Stupp, Emma; Connick, Kathy; Gomez, Onnalee; Gidudu, Jane

2016-01-01

To describe scientific information usage and publication patterns of the Centers for Disease Control and Prevention (CDC) Public Health Library and Information Center patrons. Administratively collected patron usage data and aggregate data on CDC-authored publications from the CDC Library for 3 consecutive years were analyzed. The CDC Public Health Library and Information Center, which serves CDC employees nationally and internationally. Internal patrons and external users of the CDC Library. Three-year trends in full-text article publication and downloads including most common journals used for each purpose, systematic literature searches requested and completed, and subscriptions to a weekly public health current literature awareness service. From 2011 to 2013, CDC scientists published a total of 7718 articles in the peer-reviewed literature. During the same period, article downloads from the CDC Library increased 25% to more than 1.1 million, completed requests for reviews of the scientific literature increased by 34%, and electronic subscriptions to literature compilation services increased by 23%. CDC's scientific output and information use via the CDC Library are both increasing. Researchers and field staff are making greater use of literature review services and other customized information content delivery. Virtual public health library access is an increasingly important resource for the scientific practice of public health.

Drink Specials and the Intoxication Levels of Patrons Exiting College Bars

Science.gov (United States)

Thombs, Dennis L.; Dodd, Virginia; Porkorny, Steven B.; Omli, Morrow R.; O'Mara, Ryan; Webb, Monica C.; Lacaci, Diana M.; Werch, Chad

2008-01-01

Objectives: To determine whether drink specials independently increase patrons' risk of achieving a high level of intoxication upon exiting drinking establishments. Methods: In a campus community, data were collected from exiting patrons (N=291) via sidewalk interviews and breath tests on 6 nights of 2 consecutive semesters. Results: A…

Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation.

Science.gov (United States)

Conde, Carlos; Osswald, Mariana; Barbosa, João; Moutinho-Santos, Tatiana; Pinheiro, Diana; Guimarães, Sofia; Matos, Irina; Maiato, Helder; Sunkel, Claudio E

2013-06-12

Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.

CDC STATE System E-Cigarette Legislation - Youth Access

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Youth Access....

CDC releases ventilator-associated events criteria

Directory of Open Access Journals (Sweden)

Robbins RA

2017-01-01

Full Text Available No abstract available. Article truncated at 150 words. A new term has been coined by the CDC, ventilator-associated events (VAEs (1. In 2011, the CDC convened a working group composed of members of several stakeholder organizations to address the limitations of the definition of ventilator-associated pneumonia (VAP definition (2. The organizations represented in the Working Group include: the Critical Care Societies Collaborative (the American Association of Critical-Care Nurses, the American College of Chest Physicians, the American Thoracic Society, and the Society for Critical Care Medicine; the American Association for Respiratory Care; the Association of Professionals in Infection Control and Epidemiology; the Council of State and Territorial Epidemiologists; the Healthcare Infection Control Practices Advisory Committee’s Surveillance Working Group; the Infectious Diseases Society of America; and the Society for Healthcare Epidemiology of America. VAEs are defined by an increase oxygen (>0.2 in FiO2 or positive end-expiratory pressure (PEEP (≥3 cm H2O, after a previous stable baseline of at least 2 …

CDC Vital Signs-Safer Food Saves Lives

Centers for Disease Control (CDC) Podcasts

This podcast is based on the November 2015 CDC Vital Signs report. Contaminated food sent to several states can cause multistate outbreaks of foodborne illness and make a lot of people seriously ill. Learn what can be done to prevent and stop outbreaks.

CDC Vital Signs: Teen Drinking and Driving

Science.gov (United States)

... short. Obey speed limits. Never use a cell phone or text while driving. Parents can Understand that most teens who drink ... number of teen passengers Never use a cell phone or text while driving Obey speed limits Get your copy of CDC's ...

CDC STATE System Tobacco Legislation - Smokefree Indoor Air

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Indoor Air. The...

Door locking and exit security measures on acute psychiatric admission wards

NARCIS (Netherlands)

Nijman, H.L.I.; Bowers, L.; Haglund, K.; Muir-Cochrane, E.; Simpson, A.; Merwe, M. van der

2011-01-01

Locking the exit doors of psychiatric wards is believed to reduce the risk of patients absconding. The aims of the study were to investigate both the prevalence of door locking and other exit security measures on UK admission wards, as well as whether door locking appears to be effective in keeping

Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1

DEFF Research Database (Denmark)

Du, Dan; Pedersen, Esben; Wang, Zhipeng

2008-01-01

Cell-cell contacts are crucial for the integrity of all tissues. Contrasting reports have been published about the role of Cdc42 in epithelial cell-cell contacts in vitro. In keratinocytes, it was suggested that Rac1 and not Cdc42 is crucial for the formation of mature epithelial junctions, based...... on dominant negative inhibition experiments. Deletion of the Cdc42 gene in keratinocytes in vivo slowly impaired the maintenance of cell-cell contacts by an increased degradation of beta-catenin. Whether Cdc42 is required for the formation of mature junctions was not tested. We show now that Cdc42-deficient...... immortalized and primary keratinocytes form only punctate primordial cell contacts in vitro, which cannot mature into belt-like junctions. This defect was independent of enhanced degradation of beta-catenin, but correlated to an impaired activation and localization of aPKCzeta in the Cdc42-null keratinocytes...

Distinct pools of cdc25C are phosphorylated on specific TP sites and differentially localized in human mitotic cells.

Directory of Open Access Journals (Sweden)

Celine Franckhauser

Full Text Available BACKGROUND: The dual specificity phosphatase cdc25C was the first human cdc25 family member found to be essential in the activation of cdk1/cyclin B1 that takes place at the entry into mitosis. Human cdc25C is phosphorylated on Proline-dependent SP and TP sites when it becomes active at mitosis and the prevalent model is that this phosphorylation/activation of cdc25C would be part of an amplification loop with cdk1/cyclin B1. METHODOLOGY/PRINCIPAL FINDINGS: Using highly specific antibodies directed against cdc25C phospho-epitopes, pT67 and pT130, we show here that these two phospho-forms of cdc25C represent distinct pools with differential localization during human mitosis. Phosphorylation on T67 occurs from prophase and the cdc25C-pT67 phospho-isoform closely localizes with condensed chromosomes throughout mitosis. The phospho-T130 form of cdc25C arises in late G2 and associates predominantly with centrosomes from prophase to anaphase B where it colocalizes with Plk1. As shown by immunoprecipitation of each isoform, these two phospho-forms are not simultaneously phosphorylated on the other mitotic TP sites or associated with one another. Phospho-T67 cdc25C co-precipitates with MPM2-reactive proteins while pT130-cdc25C is associated with Plk1. Interaction and colocalization of phosphoT130-cdc25C with Plk1 demonstrate in living cells, that the sequence around pT130 acts as a true Polo Box Domain (PBD binding site as previously identified from in vitro peptide screening studies. Overexpression of non-phosphorylatable alanine mutant forms for each isoform, but not wild type cdc25C, strongly impairs mitotic progression showing the functional requirement for each site-specific phosphorylation of cdc25C at mitosis. CONCLUSIONS/SIGNIFICANCE: These results show for the first time that in human mitosis, distinct phospho-isoforms of cdc25C exist with different localizations and interacting partners, thus implying that the long-standing model of a cdc25C

The autophosphorylation and p34cdc2 phosphorylation sites of casein kinase-2 beta-subunit are not essential for reconstituting the fully-active heterotetrameric holoenzyme

DEFF Research Database (Denmark)

Meggio, F; Boldyreff, B; Issinger, O G

1993-01-01

Two mutants of human casein kinase-2 beta-subunit with short deletions at either their amino (delta 1-4) or carboxy (delta 209-215) terminal side have been created that have lost the capability to undergo autophosphorylation and p34cdc2 mediated phosphorylation, respectively. Both mutants give rise...

Science in Emergency Response at CDC: Structure and Functions.

Science.gov (United States)

Iskander, John; Rose, Dale A; Ghiya, Neelam D

2017-09-01

Recent high-profile activations of the US Centers for Disease Control and Prevention (CDC) Emergency Operations Center (EOC) include responses to the West African Ebola and Zika virus epidemics. Within the EOC, emergency responses are organized according to the Incident Management System, which provides a standardized structure and chain of command, regardless of whether the EOC activation occurs in response to an outbreak, natural disaster, or other type of public health emergency. By embedding key scientific roles, such as the associate director for science, and functions within a Scientific Response Section, the current CDC emergency response structure ensures that both urgent and important science issues receive needed attention. Key functions during emergency responses include internal coordination of scientific work, data management, information dissemination, and scientific publication. We describe a case example involving the ongoing Zika virus response that demonstrates how the scientific response structure can be used to rapidly produce high-quality science needed to answer urgent public health questions and guide policy. Within the context of emergency response, longer-term priorities at CDC include both streamlining administrative requirements and funding mechanisms for scientific research.

EXIT Chart Analysis of Binary Message-Passing Decoders

DEFF Research Database (Denmark)

Lechner, Gottfried; Pedersen, Troels; Kramer, Gerhard

2007-01-01

Binary message-passing decoders for LDPC codes are analyzed using EXIT charts. For the analysis, the variable node decoder performs all computations in the L-value domain. For the special case of a hard decision channel, this leads to the well know Gallager B algorithm, while the analysis can...... be extended to channels with larger output alphabets. By increasing the output alphabet from hard decisions to four symbols, a gain of more than 1.0 dB is achieved using optimized codes. For this code optimization, the mixing property of EXIT functions has to be modified to the case of binary message......-passing decoders....

CDC WONDER: Vaccine Adverse Event Reporting System (VAERS)

Data.gov (United States)

U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination, by...

CDC STATE System Tobacco Legislation - Smokefree Indoor Air

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Indoor Air....

CDC WONDER: Compressed Mortality - Underlying Cause of Death

Data.gov (United States)

U.S. Department of Health & Human Services — The CDC WONDER Mortality - Underlying Cause of Death online database is a county-level national mortality and population database spanning the years since 1979...

Predicting The Exit Time Of Employees In An Organization Using Statistical Model

Directory of Open Access Journals (Sweden)

Ahmed Al Kuwaiti

2015-08-01

Full Text Available Employees are considered as an asset to any organization and each organization provide a better and flexible working environment to retain its best and resourceful workforce. As such continuous efforts are being taken to avoid or extend the exitwithdrawal of employees from the organization. Human resource managers are facing a challenge to predict the exit time of employees and there is no precise model existing at present in the literature. This study has been conducted to predict the probability of exit of an employee in an organization using appropriate statistical model. Accordingly authors designed a model using Additive Weibull distribution to predict the expected exit time of employee in an organization. In addition a Shock model approach is also executed to check how well the Additive Weibull distribution suits in an organization. The analytical results showed that when the inter-arrival time increases the expected time for the employees to exit also increases. This study concluded that Additive Weibull distribution can be considered as an alternative in the place of Shock model approach to predict the exit time of employee in an organization.

G Protein-coupled Receptors and Resistance to Inhibitors of Cholinesterase-8A (Ric-8A) Both Regulate the Regulator of G Protein Signaling 14 (RGS14)·Gαi1 Complex in Live Cells*

OpenAIRE

Vellano, Christopher P.; Maher, Ellen M.; Hepler, John R.; Blumer, Joe B.

2011-01-01

Background: Regulator of G protein signaling 14 (RGS14) is a G protein regulatory (GPR) protein that participates in unconventional G protein signaling independent of G protein-coupled receptors (GPCRs).

CDC Vital Signs-Preventing Melanoma

Centers for Disease Control (CDC) Podcasts

2015-06-02

This podcast is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application

Science.gov (United States)

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.; Mundy, Michael B.

2015-07-21

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application, including: identifying a subset of compute nodes in the parallel computer to execute the parallel application; selecting one compute node in the subset of compute nodes in the parallel computer as a job leader compute node; initiating execution of the parallel application on the subset of compute nodes; receiving an exit status from each compute node in the subset of compute nodes, where the exit status for each compute node includes information describing execution of some portion of the parallel application by the compute node; aggregating each exit status from each compute node in the subset of compute nodes; and sending an aggregated exit status for the subset of compute nodes in the parallel computer.

Comparison of exit time moment spectra for extrinsic metric balls

DEFF Research Database (Denmark)

Hurtado, Ana; Markvorsen, Steen; Palmer, Vicente

2012-01-01

We prove explicit upper and lower bounds for the $L^1$-moment spectra for the Brownian motion exit time from extrinsic metric balls of submanifolds $P^m$ in ambient Riemannian spaces $N^n$. We assume that $P$ and $N$ both have controlled radial curvatures (mean curvature and sectional curvature...... obtain new intrinsic comparison results for the exit time spectra for metric balls in the ambient manifolds $N^n$ themselves....

Improving nuclear regulation. NEA regulatory guidance booklets volumes 1-14

International Nuclear Information System (INIS)

2011-01-01

A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are continuously maintained and operated in an acceptably safe manner. In meeting this objective the regulator must bear in mind that it is the operator that has responsibility for safely operating the nuclear facility; the role of the regulator is to assess and to provide assurance regarding the operator's activities in terms of assuming that responsibility. The full series of these reports was brought together in one edition for the first time in 2009 and was widely found to be a useful resource. This second edition comprises 14 volumes, including the latest on The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services. The reports address various challenges that could apply throughout the lifetime of a nuclear facility, including design, siting, manufacturing, construction, commissioning, operation, maintenance and decommissioning. The compilation is intended to serve as a knowledge management tool both for current regulators and the new nuclear professionals and organisations entering the regulatory field. Contents: Executive Summary; Regulatory Challenges: 1. The Role of the Nuclear Regulator in Promoting and Evaluating Safety Culture; 2. Regulatory Response Strategies for Safety Culture Problems; 3. Nuclear Regulatory Challenges Related to Human Performance; 4. Regulatory Challenges in Using Nuclear Operating Experience; 5. Nuclear Regulatory Review of Licensee Self-assessment (LSA); 6. Nuclear Regulatory Challenges Arising from Competition in Electricity Markets; 7. The Nuclear Regulatory Challenge of Judging Safety Back-fits; 8. The Regulatory Challenges of Decommissioning Nuclear Reactors; 9. The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services

Formal procedures of the exit from a community for a university social media agency

OpenAIRE

Peleschyshyn, Andriy; Peleschyshyn, Oksana; Korzh, Roman

2016-01-01

The aim of the paper is to consider the process of exiting of a university from an online community. The importance of performing the task of exiting in a proper way is proved. Preconditions and risks of the process are investigated. All the stages of the suggested algorithm for exiting from online community are scrutinized.

CDC STATE System E-Cigarette Legislation - Youth Access

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Youth Access....

Efficiency, Leverage and Exit: The Role of Information Asymmetry in Concentrated Industries

DEFF Research Database (Denmark)

Siyahhan, Baran

2011-01-01

This paper develops a real options model of imperfect competition with asymmetric information that analyzes firms’ exit decisions. Optimal exit decision is linked to firm characteristics such as financial leverage and efficiency. The model shows that informational asymmetries can lead more...

Efficiency, Leverage and Exit: The Role of Information Asymmetry in Concentrated Industries

DEFF Research Database (Denmark)

Siyahhan, Baran

This paper develops a real options model of imperfect competition with asymmetric information that analyzes firms’ exit decisions. Optimal exit decision is linked to firm characteristics such as financial leverage and efficiency. The model shows that informational asymmetries can lead more...

3% Amuchina is as effective as the 50% concentration in the prevention of exit-site infection in children on chronic peritoneal dialysis.

Science.gov (United States)

Grosman, Mònica D; Mosquera, Vanesa M; Hernandez, Maria G; Agostini, Silvana; Adragna, Marta; Sojo, Ernesto T

2005-01-01

In a previous communication, we demonstrated that, in the prevention of exit-site infection (ESI) in children, the cleansing agent 50% Amuchina (electrolytic chloroxidizer. Amuchina SpA, Genoa, Italy) is more effective than 10% povidone iodine and as effective as 4% chlorhexidine, but with fewer adverse secondary effects. In the present study, we assessed, in an Argentine pediatric population, whether Amuchina 3% is as effective as Amuchina 50% in preventing ESI in children on chronic peritoneal dialysis. In an open-label, single-center prospective study, 27 children (mean age: 7.2 years; range: 1.7-17 years) used 3% Amuchina as a cleansing agent for the daily care of a healthy exit site. Of the 27 children, 14 were switched from 50% Amuchina to 3% Amuchina, and 13 were using the 3% Amuchina for the first time. The control group consisted of 18 patients who had previously used 50% Amuchina as a cleansing agent. We followed the recommendations of the International Society for Peritoneal Dialysis with regard to exit-site care, which include keeping the cleansing agent out of the sinus and rinsing the exit site with sterile water. Amuchina was used from the first post-implantation care of the exit site. No adverse secondary effects were seen with the use of Amuchina at either concentration. Patients using 3% Amuchina presented an ESI rate similar to that of patients using Amuchina 50%. The cost of 3% Amuchina was significantly lower than that of the 50% concentration, and it was even lower than the cost for 10% povidone iodine or 4% chlorhexidine. Although more research trials are needed to assess the efficacy of 3% Amuchina, we conclude that 3% Amuchina is the best and most cost-effective cleansing agent for the daily care of a healthy exit site in children on chronic peritoneal dialysis.

Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells

Directory of Open Access Journals (Sweden)

Samuel Rogers

2015-12-01

Full Text Available The presence or absence of a phosphorylation on a substrate at any particular point in time is a functional readout of the balance in activity between the regulatory kinase and the counteracting phosphatase. Understanding how stable or short-lived a phosphorylation site is required for fully appreciating the biological consequences of the phosphorylation. Our current understanding of kinases and their substrates is well established; however, the role phosphatases play is less understood. Therefore, we utilized a phosphatase dependent model of mitotic exit to identify potential substrates that are preferentially dephosphorylated. Using this method, we identified >16,000 phosphosites on >3300 unique proteins, and quantified the temporal phosphorylation changes that occur during early mitotic exit (McCloy et al., 2015 [1]. Furthermore, we annotated the majority of these phosphorylation sites with a high confidence upstream kinase using published, motif and prediction based methods. The results from this study have been deposited into the ProteomeXchange repository with identifier PXD001559. Here we provide additional analysis of this dataset; for each of the major mitotic kinases we identified motifs that correlated strongly with phosphorylation status. These motifs could be used to predict the stability of phosphorylated residues in proteins of interest, and help infer potential functional roles for uncharacterized phosphorylations. In addition, we provide validation at the single cell level that serine residues phosphorylated by Cdk are stable during phosphatase dependent mitotic exit. In summary, this unique dataset contains information on the temporal mitotic stability of thousands of phosphorylation sites regulated by dozens of kinases, and information on the potential preference that phosphatases have at both the protein and individual phosphosite level. The compellation of this data provides an invaluable resource for the wider research

CDC WONDER: Daily Air Temperatures and Heat Index

Data.gov (United States)

U.S. Department of Health & Human Services — The Daily Air Temperature and Heat Index data available on CDC WONDER are county-level daily average air temperatures and heat index measures spanning the years...

CDC WONDER: Detailed Mortality - Underlying Cause of Death

Data.gov (United States)

U.S. Department of Health & Human Services — The Detailed Mortality - Underlying Cause of Death data on CDC WONDER are county-level national mortality and population data spanning the years 1999-2009. Data are...

FDA-CDC Antimicrobial Resistance Isolate Bank: a Publicly Available Resource To Support Research, Development, and Regulatory Requirements.

Science.gov (United States)

Lutgring, Joseph D; Machado, María-José; Benahmed, Faiza H; Conville, Patricia; Shawar, Ribhi M; Patel, Jean; Brown, Allison C

2018-02-01

The FDA-CDC Antimicrobial Resistance Isolate Bank was created in July 2015 as a publicly available resource to combat antimicrobial resistance. It is a curated repository of bacterial isolates with an assortment of clinically important resistance mechanisms that have been phenotypically and genotypically characterized. In the first 2 years of operation, the bank offered 14 panels comprising 496 unique isolates and had filled 486 orders from 394 institutions throughout the United States. New panels are being added. Copyright © 2018 American Society for Microbiology.

Functional mapping of the fission yeast DNA polymerase δ B-subunit Cdc1 by site-directed and random pentapeptide insertion mutagenesis

Directory of Open Access Journals (Sweden)

Gray Fiona C

2009-08-01

Full Text Available Abstract Background DNA polymerase δ plays an essential role in chromosomal DNA replication in eukaryotic cells, being responsible for synthesising the bulk of the lagging strand. In fission yeast, Pol δ is a heterotetrameric enzyme comprising four evolutionarily well-conserved proteins: the catalytic subunit Pol3 and three smaller subunits Cdc1, Cdc27 and Cdm1. Pol3 binds directly to the B-subunit, Cdc1, which in turn binds the C-subunit, Cdc27. Human Pol δ comprises the same four subunits, and the crystal structure was recently reported of a complex of human p50 and the N-terminal domain of p66, the human orthologues of Cdc1 and Cdc27, respectively. Results To gain insights into the structure and function of Cdc1, random and directed mutagenesis techniques were used to create a collection of thirty alleles encoding mutant Cdc1 proteins. Each allele was tested for function in fission yeast and for binding of the altered protein to Pol3 and Cdc27 using the two-hybrid system. Additionally, the locations of the amino acid changes in each protein were mapped onto the three-dimensional structure of human p50. The results obtained from these studies identify amino acid residues and regions within the Cdc1 protein that are essential for interaction with Pol3 and Cdc27 and for in vivo function. Mutations specifically defective in Pol3-Cdc1 interactions allow the identification of a possible Pol3 binding surface on Cdc1. Conclusion In the absence of a three-dimensional structure of the entire Pol δ complex, the results of this study highlight regions in Cdc1 that are vital for protein function in vivo and provide valuable clues to possible protein-protein interaction surfaces on the Cdc1 protein that will be important targets for further study.

Regulation of Biotechnology in Cameroon W

African Journals Online (AJOL)

... security and public health are high on government's policy agenda. ... tion by the Cameroon Development Corporation. (CDC) of a ... can model law on Safety in Biotechnology (and the Convention ..... its biosafety regulation on liability and redress in due course. ... in Kuala Lumpur, Malaysia in February this year. (2004).

Toward 3D structural information from quantitative electron exit wave analysis

International Nuclear Information System (INIS)

Borisenko, Konstantin B; Moldovan, Grigore; Kirkland, Angus I; Wang, Amy; Van Dyck, Dirk; Chen, Fu-Rong

2012-01-01

Simulations show that using a new direct imaging detector and accurate exit wave restoration algorithms allows nearly quantitative restoration of electron exit wave phase, which can be regarded as only qualitative for conventional indirect imaging cameras. This opens up a possibility of extracting accurate information on 3D atomic structure of the sample even from a single projection.

CDC Vital Signs: Tobacco Use and Secondhand Smoke

Science.gov (United States)

... on youth access to tobacco products and tobacco marketing to youth, and closely follow them. Check the ... Director for Communications (OADC) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding ...

Cdc20 is critical for meiosis I and fertility of female mice.

Directory of Open Access Journals (Sweden)

Fang Jin

2010-09-01

Full Text Available Chromosome missegregation in germ cells is an important cause of unexplained infertility, miscarriages, and congenital birth defects in humans. However, the molecular defects that lead to production of aneuploid gametes are largely unknown. Cdc20, the activating subunit of the anaphase-promoting complex/cyclosome (APC/C, initiates sister-chromatid separation by ordering the destruction of two key anaphase inhibitors, cyclin B1 and securin, at the transition from metaphase to anaphase. The physiological significance and full repertoire of functions of mammalian Cdc20 are unclear at present, mainly because of the essential nature of this protein in cell cycle progression. To bypass this problem we generated hypomorphic mice that express low amounts of Cdc20. These mice are healthy and have a normal lifespan, but females produce either no or very few offspring, despite normal folliculogenesis and fertilization rates. When mated with wild-type males, hypomorphic females yield nearly normal numbers of fertilized eggs, but as these embryos develop, they become malformed and rarely reach the blastocyst stage. In exploring the underlying mechanism, we uncover that the vast majority of these embryos have abnormal chromosome numbers, primarily due to chromosome lagging and chromosome misalignment during meiosis I in the oocyte. Furthermore, cyclin B1, cyclin A2, and securin are inefficiently degraded in metaphase I; and anaphase I onset is markedly delayed. These results demonstrate that the physiologically effective threshold level of Cdc20 is high for female meiosis I and identify Cdc20 hypomorphism as a mechanism for chromosome missegregation and formation of aneuploid gametes.

CDC Vital Signs-Protect Patients from Antibiotic Resistance

Centers for Disease Control (CDC) Podcasts

This podcast is based on the March 2016 CDC Vital Signs report. Patients can get serious healthcare-associated infections, or HAIs, while receiving medical treatment in a healthcare facility. Learn how to prevent healthcare-associated infections.

CDC Vital Signs-Too Loud for Too Long!

Centers for Disease Control (CDC) Podcasts

This podcast is based on the February 2017 CDC Vital Signs report. Being around too much loud noise-like a leaf blower or rock concert-can cause permanent hearing loss. Learn how to prevent hearing loss.

Association Between Health Plan Exit From Medicaid Managed Care and Quality of Care, 2006-2014.

Science.gov (United States)

Ndumele, Chima D; Schpero, William L; Schlesinger, Mark J; Trivedi, Amal N

2017-06-27

State Medicaid programs have increasingly contracted with insurers to provide medical care services for enrollees (Medicaid managed care plans). Insurers that provide these plans can exit Medicaid programs each year, with unclear effects on quality of care and health care experiences. To determine the frequency and interstate variation of health plan exit from Medicaid managed care and evaluate the relationship between health plan exit and market-level quality. Retrospective cohort of all comprehensive Medicaid managed care plans (N = 390) during the interval 2006-2014. Plan exit, defined as the withdrawal of a managed care plan from a state's Medicaid program. Eight measures from the Healthcare Effectiveness Data and Information Set were used to construct 3 composite indicators of quality (preventive care, chronic disease care management, and maternity care). Four measures from the Consumer Assessment of Healthcare Providers and Systems were combined into a composite indicator of patient experience, reflecting the proportion of beneficiaries rating experiences as 8 or above on a 0-to-10-point scale. Outcome data were available for 248 plans (68% of plans operating prior to 2014, representing 78% of beneficiaries). Of the 366 comprehensive Medicaid managed care plans operating prior to 2014, 106 exited Medicaid. These exiting plans enrolled 4 848 310 Medicaid beneficiaries, with a mean of 606 039 beneficiaries affected by plan exits annually. Six states had a mean of greater than 10% of Medicaid managed care recipients enrolled in plans that exited, whereas 10 states experienced no plan exits. Plans that exited from a state's Medicaid market performed significantly worse prior to exiting than those that remained in terms of preventive care (57.5% vs 60.4%; difference, 2.9% [95% CI, 0.3% to 5.5%]), maternity care (69.7% vs 73.6%; difference, 3.8% [95% CI, 1.7% to 6.0%]), and patient experience (73.5% vs 74.8%; difference, 1.3% [95% CI, 0.6% to 1

Stor forskel på kommuners bande-exit

DEFF Research Database (Denmark)

Mørck, Line Lerche

2015-01-01

DEBAT: Kommunerne har meget forskellige exit-tilbud til bande- og rockermedlemmer. Der er brug for mere indgående forskning, så vi ved, hvad der virker bedst, skriver Line Lerche Mørck, lektor i pædagogisk psykologi....

Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.

Science.gov (United States)

Lee, Mei-Chin; Shei, William; Chan, Anita S; Chua, Boon-Tin; Goh, Shuang-Ru; Chong, Yaan-Fun; Hilmy, Maryam H; Nongpiur, Monisha E; Baskaran, Mani; Khor, Chiea-Chuen; Aung, Tin; Hunziker, Walter; Vithana, Eranga N

2017-10-15

PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tendances Carbone no. 82 'A 2030 framework for climate and energy policies: CDC Climat Research's answer'

International Nuclear Information System (INIS)

2013-01-01

Among the publications of CDC Climat Research, 'Tendances Carbone' bulletin specifically studies the developments of the European market for CO 2 allowances. This issue addresses the following points: To establish a climate and energy policy in the EU in 2030, CDC Climat Research addresses three main recommendations to the European Commission: (1) Establish a binding, single and ambitious CO 2 emission reduction target of at least 40% in 2030. (2) Put the EU ETS as the central and non-residual instrument aimed at promoting cost-effective reductions in Europe and other parts of the world. (3) Define a stable, predictable and flexible climate regulation to limit carbon leakage and encourage innovation. Key drivers of the European carbon price this month: - The European Parliament has adopted Back-loading: 1.85 billion EUAs will be sold at auction between now and 2015 instead of 2.75 billion; - Phase 2 compliance: a surplus of 1,742 million tonnes (excluding the aviation sector) including auctions. - Energy Efficiency Directive: 22 of the 27 Member States have forwarded indicative targets for 2020 to the European Commission; these targets will be assessed in early 2014

The DNA repair capability of cdc9, the saccharomyces cerevisiae mutant defective in DNA ligase

International Nuclear Information System (INIS)

Johnston, L.H.

1979-01-01

The cell cycle mutant, cdc9, in the yeast Saccharomyces cerevisiae is defective in DNA ligase with the consequence to be deficient in the repair of DNA damaged by methyl methane sulphonate. On the other hand survival of cdc9 after irradiation by γ-rays is little different from that of the wild-type, even after a period of stress at the restrictive temperature. The mutant cdc9 is not allelic with any known rad or mms mutants. (orig./AJ) [de

Exit Polling in an Emergent Democracy: The Complex Case of Ukraine

Directory of Open Access Journals (Sweden)

Natalya Nikolaevna Kharchenko

2010-05-01

Full Text Available This report considers the methodological specifics of conducting exit polls to verify election returns, mainly using an example of election campaigns in Ukraine from 2002-2007. The deepest public resonance was aroused by exit polls conducted after the second round of Ukrainian presidential elections in 2004. These polls were one of the factors, which led to massive demonstrations (the so-called "Orange Revolution" and the revocation of election results. The authors show that in the environment of administrative pressure on voters, governmental control of mass media, and severe political struggle, inaccuracy increases. Thus, to acquire reliable and valid information, the polling methods used must be modified. The recommendations given for the methodology of conducting exit polls may be useful for emergent democratic countries.

CDC Vital Signs: Daily Pill Can Prevent HIV

Science.gov (United States)

... risk about PrEP through health department programs, social marketing campaigns, and other training and technical assistance efforts. ... MB] en Español [PDF – 2.7 MB] CDC Digital Press Kit MMWR Article 1 MMWR Article 2 ...

Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors.

Science.gov (United States)

Kast, David J; Yang, Changsong; Disanza, Andrea; Boczkowska, Malgorzata; Madasu, Yadaiah; Scita, Giorgio; Svitkina, Tatyana; Dominguez, Roberto

2014-04-01

The Rho family GTPase effector IRSp53 has essential roles in filopodia formation and neuronal development, but its regulatory mechanism is poorly understood. IRSp53 contains a membrane-binding BAR domain followed by an unconventional CRIB motif that overlaps with a proline-rich region (CRIB-PR) and an SH3 domain that recruits actin cytoskeleton effectors. Using a fluorescence reporter assay, we show that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB-PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain. The crystal structure of Cdc42 bound to the CRIB-PR reveals a new mode of effector binding to Rho family GTPases. Structure-inspired mutations disrupt autoinhibition and Cdc42 binding in vitro and decouple Cdc42- and IRSp53-dependent filopodia formation in cells. The data support a combinatorial mechanism of IRSp53 activation.

CDC STATE System E-Cigarette Legislation - Smokefree Indoor Air

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Smokefree...

Multiple domains of fission yeast Cdc19p (MCM2) are required for its association with the core MCM complex.

Science.gov (United States)

Sherman, D A; Pasion, S G; Forsburg, S L

1998-07-01

The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function.

The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing

DEFF Research Database (Denmark)

Lischetti, Tiziana; Zhang, Gang; Sedgwick, Garry G

2014-01-01

Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, Mad2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of Cdc20 kinetochore localization...... in the SAC, we delineate the molecular details of its interaction with kinetochores. We find that BubR1 recruits the bulk of Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). We show that preventing Cdc20 kinetochore localization by removal of the IC20BD has a limited effect...... on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signalling and SAC...

Experience in programming Assembly language of CDC CYBER 170/750 computer

International Nuclear Information System (INIS)

Caldeira, A.D.

1987-10-01

Aiming to optimize processing time of BCG computer code in the CDC CYBER 170/750 computer, the FORTRAN-V language of INTERP subroutine was converted to Assembly language. The BCG code was developed for solving neutron transport equation by iterative method, and the INTERP subroutine is innermost loop of the code carrying out 5 interpolation types. The central processor unit Assembly language of the CDC CYBER 170/750 computer and its application in implementing the interpolation subroutine of BCG code are described. (M.C.K.)

A Diversity Exit Interview/Survey for the Military

National Research Council Canada - National Science Library

Knouse, Stephen

2001-01-01

The exit interview and survey are means for identifying organizational problems, including diversity issues, through individuals separating from the organization, who are in a unique position to supply candid feedback...

Symmetry associated with symmetry break: Revisiting ants and humans escaping from multiple-exit rooms

Science.gov (United States)

Ji, Q.; Xin, C.; Tang, S. X.; Huang, J. P.

2018-02-01

Crowd panic has incurred massive injuries or deaths throughout the world, and thus understanding it is particularly important. It is now a common knowledge that crowd panic induces "symmetry break" in which some exits are jammed while others are underutilized. Amazingly, here we show, by experiment, simulation and theory, that a class of symmetry patterns come to appear for ants and humans escaping from multiple-exit rooms while the symmetry break exists. Our symmetry pattern is described by the fact that the ratio between the ensemble-averaging numbers of ants or humans escaping from different exits is equal to the ratio between the widths of the exits. The mechanism lies in the effect of heterogeneous preferences of agents with limited information for achieving the Nash equilibrium. This work offers new insights into how to improve public safety because large public areas are always equipped with multiple exits, and it also brings an ensemble-averaging method for seeking symmetry associated with symmetry breaking.

Exits from Temporary Jobs in Europe: A Competing Risks Analysis

DEFF Research Database (Denmark)

D'Addio, Anna Christina; Rosholm, Michael

2005-01-01

We study transitions out of temporary jobs using the waves 1994-1999 of the European Community Household Panel applying a discrete time duration model. Specifically, we use a multinomial logitmodel distinguishing between exits into permanent employment and non-employment. Two different specificat......We study transitions out of temporary jobs using the waves 1994-1999 of the European Community Household Panel applying a discrete time duration model. Specifically, we use a multinomial logitmodel distinguishing between exits into permanent employment and non-employment. Two different...

Mechanism of APC/CCDC20 activation by mitotic phosphorylation.

Science.gov (United States)

Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya; Brown, Nicholas G; VanderLinden, Ryan; Imre, Richard; Jarvis, Marc A; Brunner, Michael R; Davidson, Iain F; Litos, Gabriele; Haselbach, David; Mechtler, Karl; Stark, Holger; Schulman, Brenda A; Peters, Jan-Michael

2016-05-10

Chromosome segregation and mitotic exit are initiated by the 1.2-MDa ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) and its coactivator CDC20 (cell division cycle 20). To avoid chromosome missegregation, APC/C(CDC20) activation is tightly controlled. CDC20 only associates with APC/C in mitosis when APC/C has become phosphorylated and is further inhibited by a mitotic checkpoint complex until all chromosomes are bioriented on the spindle. APC/C contains 14 different types of subunits, most of which are phosphorylated in mitosis on multiple sites. However, it is unknown which of these phospho-sites enable APC/C(CDC20) activation and by which mechanism. Here we have identified 68 evolutionarily conserved mitotic phospho-sites on human APC/C bound to CDC20 and have used the biGBac technique to generate 47 APC/C mutants in which either all 68 sites or subsets of them were replaced by nonphosphorylatable or phospho-mimicking residues. The characterization of these complexes in substrate ubiquitination and degradation assays indicates that phosphorylation of an N-terminal loop region in APC1 is sufficient for binding and activation of APC/C by CDC20. Deletion of the N-terminal APC1 loop enables APC/C(CDC20) activation in the absence of mitotic phosphorylation or phospho-mimicking mutations. These results indicate that binding of CDC20 to APC/C is normally prevented by an autoinhibitory loop in APC1 and that its mitotic phosphorylation relieves this inhibition. The predicted location of the N-terminal APC1 loop implies that this loop controls interactions between the N-terminal domain of CDC20 and APC1 and APC8. These results reveal how APC/C phosphorylation enables CDC20 to bind and activate the APC/C in mitosis.

Should all patients with hyperparathyroidism be screened for a CDC73 mutation?

Directory of Open Access Journals (Sweden)

Caroline Bachmeier

2018-03-01

Full Text Available Primary hyperparathyroidism (PH is a common endocrine abnormality and may occur as part of a genetic syndrome. Inactivating mutations of the tumour suppressor gene CDC73 have been identified as accounting for a large percentage of hyperparathyroidism-jaw tumour syndrome (HPT-JT cases and to a lesser degree account for familial isolated hyperparathyroidism (FIHP cases. Reports of CDC73 whole gene deletions are exceedingly rare. We report the case of a 39 year-old woman with PH secondary to a parathyroid adenoma associated with a large chromosomal deletion (2.5 Mb encompassing the entire CDC73 gene detected years after parathyroidectomy. This case highlights the necessity to screen young patients with hyperparathyroidism for an underlying genetic aetiology. It also demonstrates that molecular testing for this disorder should contain techniques that can detect large deletions.

Adolescents Exiting Homelessness over Two Years: The Risk Amplification and Abatement Model

Science.gov (United States)

Milburn, Norweeta G.; Rice, Eric; Rotheram-Borus, Mary Jane; Mallett, Shelley; Rosenthal, Doreen; Batterham, Phillip; May, Susanne J.; Witkin, Andrea; Duan, Naihua

2009-01-01

The Risk Amplification and Abatement Model (RAAM) demonstrates that negative contact with socializing agents amplify risk, while positive contact abates risk for homeless adolescents. To test this model, the likelihood of exiting homelessness and returning to familial housing at 2 years and stably exiting over time are examined with longitudinal…

Dangerous Creatures - A Visit to the CDC Insectary

Centers for Disease Control (CDC) Podcasts

2012-11-07

Tour CDC’s insectary with Sofi, a young host, and learn from CDC researchers about mosquitoes and insecticide resistance.  Created: 11/7/2012 by Center for Global Health (CGH).   Date Released: 12/20/2012.

Immunohistochemical detection of cdc2 is useful in predicting survival in patients with mantle cell lymphoma.

Science.gov (United States)

Hui, David; Reiman, Tony; Hanson, John; Linford, Rick; Wong, Winson; Belch, Andrew; Lai, Raymond

2005-09-01

Recent cDNA microarray studies have reported the prognostic value of several genes in mantle cell lymphoma patients. We aimed to validate the prognostic significance of three of these genes: alpha-tubulin, cdc2, and CENP-F. The protein expression of alpha-tubulin, cdc2, and CENP-F was assessed using immunohistochemistry. Their immunoreactivity in 48 formalin-fixed/paraffin-embedded mantle cell lymphoma tumors was determined by estimating the percentage of positive cells. These results were correlated with the expression of proliferation marker Ki67 and survival. Of these 48 mantle cell lymphoma patients, 41 were men and seven were women. The median age at time of diagnosis was 64.5 years, and the overall median survival was 40 months. In benign lymph nodes, the expression of cdc2 and alpha-tubulin was restricted to the germinal centers; mantle zones were negative. Expression of CENP-F was more uniformly distributed. In mantle cell lymphoma, Ki67 significantly correlated with all three markers (P50%) and cdc2 (>25%) significantly correlated with shorter survival (Por=2 correlated with worse clinical outcome, and high clinical stage (ie 4 vs cdc2 and Ki67 was independent of international prognostic index and clinical stage. We have validated the prognostic value of cdc2, and confirmed that of Ki67, in a cohort of mantle cell lymphoma patients. Immunohistochemical detection of cdc2 and Ki67 may be a useful and simple method in evaluating the prognosis of mantle cell lymphoma patients.

SCF^{Cyclin F}-dependent degradation of CDC6 suppresses DNA re-replication

DEFF Research Database (Denmark)

Walter, David; Hoffmann, Saskia; Komseli, Eirini-Stavroula

2016-01-01

interact through defined sequence motifs that promote CDC6 ubiquitylation and degradation. Absence of Cyclin F or expression of a stable mutant of CDC6 promotes re-replication and genome instability in cells lacking the CDT1 inhibitor Geminin. Together, our work reveals a novel SCF(Cyclin F...

1 CFR 21.14 - Deviations from standard organization of the Code of Federal Regulations.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Deviations from standard organization of the... CODIFICATION General Numbering § 21.14 Deviations from standard organization of the Code of Federal Regulations. (a) Any deviation from standard Code of Federal Regulations designations must be approved in advance...

Two-dimensional exit dosimetry using a liquid-filled electronic portal imaging device and a convolution model

International Nuclear Information System (INIS)

Boellaard, Ronald; Herk, Marcel van; Uiterwaal, Hans; Mijnheer, Ben

1997-01-01

Background and purpose: To determine the accuracy of two-dimensional exit dose measurements with an electronic portal imaging device, EPID, using a convolution model for a variety of clinically relevant situations. Materials and methods: Exit doses were derived from portal dose images, obtained with a liquid-filled EPID at distances of 50 cm or more behind the patient, by using a convolution model. The resulting on- and off-axis exit dose values were first compared with ionization chamber exit dose measurements for homogeneous and inhomogeneous phantoms in open and wedged 4,8 and 18 MV photon beams. The accuracy of the EPID exit dose measurements was then determined for a number of anthropomorphic phantoms (lung and larynx) irradiated under clinical conditions and for a few patients treated in an 8 MV beam. The latter results were compared with in vivo exit dose measurements using diodes. Results: The exit dose can be determined from portal images with an accuracy of 1.2% (1 SD) compared with ionization chamber measurements for open beams and homogeneous phantoms at all tested beam qualities. In the presence of wedges and for inhomogeneous phantoms the average relative accuracy slightly deteriorated to 1.7% (1 SD). For lung phantoms in a 4 MV beam a similar accuracy was obtained after refinement of our convolution model, which requires knowledge of the patient contour. Differences between diode and EPID exit dose measurements for an anthropomorphic lung phantom in an 8 MV beam were 2.5% at most, with an average agreement within 1% (1 SD). For larynx phantoms in a 4 MV beam exit doses obtained with an ionization chamber and EPID agreed within 1.5% (1 SD). Finally, exit doses in a few patients irradiated in an 8 MV beam could be determined with the EPID with an accuracy of 1.1% (1 SD) relative to exit dose measurements using diodes. Conclusions: Portal images, obtained with our EPID and analyzed with our convolution model, can be used to determine the exit dose

CDC STATE System Tobacco Legislation - Smokefree Indoor Air Summary

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2018. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Indoor Air. The...

Explaining discrepancies in reproductive health indicators from population-based surveys and exit surveys: a case from Rwanda.

Science.gov (United States)

Meekers, D; Ogada, E A

2001-06-01

Reproductive health programmes often need exit surveys and population-based surveys for monitoring and evaluation. This study investigates why such studies produce discrepant estimates of condom use, sexual behaviour and condom brand knowledge, and discusses the implications for future use of exit surveys for programme monitoring. Logistic regression is used to explain differences between a household survey of 1295 persons and an exit survey among a random sample of 2550 consumers at retail outlets in RWANDA: Discrepancies in ever use of condoms and risky sexual behaviours are due to differences in socioeconomic status of the two samples. After controls, exit surveys at most outlet types have the same results as the household survey. Only exit surveys at bars, nightclubs and hotels yield significantly different estimates. However, the above-average knowledge of Prudence Plus condoms in the exit interviews is not attributable to socioeconomic or demographic variables, most likely because respondents have seen the product at the outlets. Information about condom use and sexual behaviour obtained from exit surveys appears as accurate as that obtained through household surveys. Nevertheless, exit surveys must be used cautiously. Because exit surveys may include wealthier and better-educated respondents, they are not representative of the general population. The composition of exit survey samples should be validated through existing household surveys. Comparisons across survey types are generally unadvisable, unless they control for sample differences. When generalizing to the population at large is not needed (e.g. for studies aimed at identifying the characteristics and behaviour of users of particular products or services), exit surveys can provide an appropriate alternative to household surveys.

NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling

DEFF Research Database (Denmark)

Sørensen, Claus Storgaard; Melixetian, Marina; Klein, Ditte Kjaersgaard

2010-01-01

The DNA damage induced G(2)/M checkpoint is an important guardian of the genome that prevents cell division when DNA lesions are present. The checkpoint prevents cells from entering mitosis by degrading CDC25A, a key CDK activator. CDC25A proteolysis is controlled by direct phosphorylation events...... is required for beta-TrCP mediated CDC25A polyubiquitylation and degradation. The activity of NEK11 is in turn controlled by CHK1 that activates NEK11 via phosphorylation on serine 273. Since inhibition of NEK11 activity forces checkpoint-arrested cells into mitosis and cell death, NEK11 is, like CHK1...

Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina infected with SIVmac239

Directory of Open Access Journals (Sweden)

Tian-Zhang Song

2018-01-01

Full Text Available Parasites can increase infection rates andpathogenicity in immunocompromised humanimmunodeficiency virus (HIV patients. However, invitro studies and epidemiological investigationsalso suggest that parasites might escapeimmunocompromised hosts during HIV infection.Due to the lack of direct evidence from animalexperiments, the effects of parasitic infections onimmunocompromised hosts remain unclear. Here,we detected 14 different parasites in six northernpig-tailed macaques (NPMs before or during the50th week of post-simian immunodeficiency virus(SIV infection by ELISA. The NPMs all carriedparasites before viral injection. At the 50th week afterviral injection, the individuals with negative resultsin parasitic detection (i.e., 08247 and 08287 werecharacterized as the Parasites Exit (PE group, withthe other individuals (i.e., 09203, 09211, 10205, and10225 characterized as the Parasites Remain (PRgroup. Compared with the PR group, the NPMs in thePE group showed higher viral loads, lower CD4+ Tcells counts, and lower CD4/CD8 rates. Additionally,the PE group had higher immune activation andimmune exhaustion of both CD4+ and CD8+ T cells.Pathological observation showed greater injury tothe liver, cecum, colon, spleen, and mesentericlymph nodes in the PE group. This study showedmore seriously compromised immunity in the PEgroup, strongly indicating that parasites might exit animmunocompromised host.

Computer Center CDC Libraries/NSRD (Subprograms).

Science.gov (United States)

1984-06-01

SUBROUTINE MUST BE RE-INITIALIZED USING EITHER THE THIRD OR FOURTH FORM OF THE CALL. USAGE CALL EXTPRM (IAREA, LAREA, IPARM, ISEP ) CALL EXTPRM (IAREA, LAREA...INTEGER.) IPARM - OUT - NEXT PARAMETER, LEFT-JUSTIFIED, ZERO-FILLED ISEP - OUT - IF PRESENT, CODE INDICATING TYPE OF SEPARATOR FOUND FOLLOWING THE...SYSTEMS) CDC 6000/CYBER 170 (NOS/BE) REMARKS NONE USAGE CALL PARGET (IAREA, LAREA, IPARAM, NPARAM, ISEP , RSEP, LSEP) CALL PARGET (IAREA, LAREA, IPARAM

ECIS - Adaptation to CDC CYBER system

International Nuclear Information System (INIS)

Nair, R.P.K.; Rego, R.A.; Lemos, B.J.K.C.

1981-01-01

The implantation of ECIS computer code, elaborated for BOURROUGHS 6700 computer of USP (Universidade de Sao Paulo), in the CDC CYBER 170/730 computer is presented. The ECIS code calculates cross section by coupled channel method. Some problems were calculated to verify the compactibility of results obtained from BOURROUGHS 6700 version with the version. The problems calculated by new version and the carried out modifications, are described (M.C.K.) [pt

CDC STATE System Tobacco Legislation - Smokefree Indoor Air Summary

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2017. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. Legislation – Smokefree Indoor Air....

CDC STATE System E-Cigarette Legislation - Smokefree Indoor Air

Data.gov (United States)

U.S. Department of Health & Human Services — 1995-2016. Centers for Disease Control and Prevention (CDC). State Tobacco Activities Tracking and Evaluation (STATE) System. E-Cigarette Legislation—Smokefree...

Cdc6-Induced Conformational Changes in ORC Bound to Origin DNA Revealed by Cryo-Electron Microscopy

Energy Technology Data Exchange (ETDEWEB)

Sun J.; Li H.; Kawakami, H.; Zech, J.; Speck, C.; Stillman, B.

2012-03-07

The eukaryotic origin recognition complex (ORC) interacts with and remodels origins of DNA replication prior to initiation in S phase. Here, we report a single-particle cryo-EM-derived structure of the supramolecular assembly comprising Saccharomyces cerevisiae ORC, the replication initiation factor Cdc6, and double-stranded ARS1 origin DNA in the presence of ATP{gamma}S. The six subunits of ORC are arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2. Cdc6 binding changes the conformation of ORC, in particular reorienting the Orc1 N-terminal BAH domain. Segmentation of the 3D map of ORC-Cdc6 on DNA and docking with the crystal structure of the homologous archaeal Orc1/Cdc6 protein suggest an origin DNA binding model in which the DNA tracks along the interior surface of the crescent-like ORC. Thus, ORC bends and wraps the DNA. This model is consistent with the observation that binding of a single Cdc6 extends the ORC footprint on origin DNA from both ends.

Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.

Science.gov (United States)

Liao, Yuning; Liu, Ningning; Hua, Xianliang; Cai, Jianyu; Xia, Xiaohong; Wang, Xuejun; Huang, Hongbiao; Liu, Jinbao

2017-02-02

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Ethnic variations in immigrant poverty exit and female employment: the missing link.

Science.gov (United States)

Kaida, Lisa

2015-04-01

Despite widespread interest in poverty among recent immigrants and female immigrant employment, research on the link between the two is limited. This study evaluates the effect of recently arrived immigrant women's employment on the exit from family poverty and considers the implications for ethnic differences in poverty exit. It uses the bivariate probit model and the Fairlie decomposition technique to analyze data from the Longitudinal Survey of Immigrants to Canada (LSIC), a nationally representative survey of immigrants arriving in Canada, 2000-2001. Results show that the employment of recently arrived immigrant women makes a notable contribution to lifting families out of poverty. Moreover, the wide ethnic variations in the probability of exit from poverty between European and non-European groups are partially explained by the lower employment rates among non-European women. The results suggest that the equal earner/female breadwinner model applies to low-income recent immigrant families in general, but the male breadwinner model explains the low probability of poverty exit among select non-European groups whose female employment rates are notably low.

Mean-Variance portfolio optimization when each asset has individual uncertain exit-time

Directory of Open Access Journals (Sweden)

Reza Keykhaei

2016-12-01

Full Text Available The standard Markowitz Mean-Variance optimization model is a single-period portfolio selection approach where the exit-time (or the time-horizon is deterministic. ‎In this paper we study the Mean-Variance portfolio selection problem ‎with ‎uncertain ‎exit-time ‎when ‎each ‎has ‎individual uncertain ‎xit-time‎, ‎which generalizes the Markowitz's model‎. ‎‎‎‎‎‎We provide some conditions under which the optimal portfolio of the generalized problem is independent of the exit-times distributions. Also, ‎‎it is shown that under some general circumstances, the sets of optimal portfolios‎ ‎in the generalized model and the standard model are the same‎.

Indirect semiquantitative determination of p34cdc2 levels in G1 and G2 cells of the carbohydrate-starved root meristems in Vicia faba var. minor

Directory of Open Access Journals (Sweden)

Justyna Polit

2014-01-01

Full Text Available In eukaryotes, the 34kDa kinase (p34 encoded by the cdc2 gene is a key regulator of both the onset of DNA synthesis (G1 to S phase transition and the onset of mitosis (G1 to M phase transition. Using mouse anti-human PSTAIRE and FITClabelled goat antibodies, indirect semiquantitative determination of p34cdc2 levels was performed in meristematic cells from the control (intact and excised, carbohydrate-starved main roots of Vicia faba var. minor. No evident differences in the intensity of fluorescence was found either between the G1 and G2 cells or between the control cells and the cells arrested at both Principal Control Points by carbohydrate starvation. It seems thus, that the cell cycle block induced in meristematic cells of V. faba var. minor is not correlated with the absolute level of the key cell cycle enzyme responsible for phosphory-lution of cellular proteins, but primarily with the altered activity of p34cdc2.

Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway

International Nuclear Information System (INIS)

Alleaume, Celine; Eychene, Alain; Harnois, Thomas; Bourmeyster, Nicolas; Constantin, Bruno; Caigneaux, Evelyne; Muller, Jean-Marc; Philippe, Michel

2004-01-01

Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells

Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin

DEFF Research Database (Denmark)

Woodham, Emma F; Paul, Nikki R; Tyrrell, Benjamin

2017-01-01

traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates...... multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large...... null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics....

Tunneling time, exit time and exit momentum in strong field tunnel ionization

International Nuclear Information System (INIS)

Teeny, Nicolas

2016-01-01

Tunnel ionization belongs to the fundamental processes of atomic physics. It is still an open question when does the electron tunnel ionize and how long is the duration of tunneling. In this work we solve the time-dependent Schroedinger equation in one and two dimensions and use ab initio quantum calculations in order to answer these questions. Additionally, we determine the exit momentum of the tunnel ionized electron from first principles. We find out results that are different from the assumptions of the commonly employed two-step model, which assumes that the electron ionizes at the instant of electric field maximum with a zero momentum. After determining the quantum final momentum distribution of tunnel ionized electrons we show that the two-step model fails to predict the correct final momentum. Accordingly we suggest how to correct the two-step model. Furthermore, we determine the instant at which tunnel ionization starts, which turns out to be different from the instant usually assumed. From determining the instant at which it is most probable for the electron to enter the tunneling barrier and the instant at which it exits we determine the most probable time spent under the barrier. Moreover, we apply a quantum clock approach in order to determine the duration of tunnel ionization. From the quantum clock we determine an average tunneling time which is different in magnitude and origin with respect to the most probable tunneling time. By defining a probability distribution of tunneling times using virtual detectors we relate both methods and explain the apparent discrepancy. The results found have in general an effect on the interpretation of experiments that measure the spectra of tunnel ionized electrons, and specifically on the calibration of the so called attoclock experiments, because models with imprecise assumptions are usually employed in order to interpret experimental results.

Tunneling time, exit time and exit momentum in strong field tunnel ionization

Energy Technology Data Exchange (ETDEWEB)

Teeny, Nicolas

2016-10-18

Tunnel ionization belongs to the fundamental processes of atomic physics. It is still an open question when does the electron tunnel ionize and how long is the duration of tunneling. In this work we solve the time-dependent Schroedinger equation in one and two dimensions and use ab initio quantum calculations in order to answer these questions. Additionally, we determine the exit momentum of the tunnel ionized electron from first principles. We find out results that are different from the assumptions of the commonly employed two-step model, which assumes that the electron ionizes at the instant of electric field maximum with a zero momentum. After determining the quantum final momentum distribution of tunnel ionized electrons we show that the two-step model fails to predict the correct final momentum. Accordingly we suggest how to correct the two-step model. Furthermore, we determine the instant at which tunnel ionization starts, which turns out to be different from the instant usually assumed. From determining the instant at which it is most probable for the electron to enter the tunneling barrier and the instant at which it exits we determine the most probable time spent under the barrier. Moreover, we apply a quantum clock approach in order to determine the duration of tunnel ionization. From the quantum clock we determine an average tunneling time which is different in magnitude and origin with respect to the most probable tunneling time. By defining a probability distribution of tunneling times using virtual detectors we relate both methods and explain the apparent discrepancy. The results found have in general an effect on the interpretation of experiments that measure the spectra of tunnel ionized electrons, and specifically on the calibration of the so called attoclock experiments, because models with imprecise assumptions are usually employed in order to interpret experimental results.

MRG15 activates the cdc2 promoter via histone acetylation in human cells

International Nuclear Information System (INIS)

Pena, AndreAna N.; Tominaga, Kaoru; Pereira-Smith, Olivia M.

2011-01-01

Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

MRG15 activates the cdc2 promoter via histone acetylation in human cells

Energy Technology Data Exchange (ETDEWEB)

Pena, AndreAna N., E-mail: andreana.pena@gmail.com [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Tominaga, Kaoru; Pereira-Smith, Olivia M. [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

2011-07-01

Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and migration.

Science.gov (United States)

Williams, B Blairanne; Cantrell, V Ashley; Mundell, Nathan A; Bennett, Andrea C; Quick, Rachel E; Jessen, Jason R

2012-05-01

Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes.

The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation

Science.gov (United States)

Kühn, Sonja; Erdmann, Constanze; Kage, Frieda; Block, Jennifer; Schwenkmezger, Lisa; Steffen, Anika; Rottner, Klemens; Geyer, Matthias

2015-05-01

Formins are actin polymerization factors that elongate unbranched actin filaments at the barbed end. Rho family GTPases activate Diaphanous-related formins through the relief of an autoregulatory interaction. The crystal structures of the N-terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that Cdc42 mediates contacts with all five armadillo repeats of the formin with specific interactions formed by the Rho-GTPase insert helix. Mutation of three residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a parallel coiled coil segment leads to formation of an umbrella-shaped structure that--together with Cdc42--spans more than 15 nm in diameter. The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia.

Micro-supercapacitors from carbide derived carbon (CDC) films on silicon chips

Science.gov (United States)

Huang, Peihua; Heon, Min; Pech, David; Brunet, Magali; Taberna, Pierre-Louis; Gogotsi, Yury; Lofland, Samuel; Hettinger, Jeffrey D.; Simon, Patrice

2013-03-01

Interdigitated on-chip micro-supercapacitors based on Carbide Derived Carbon (CDC) films were fabricated and tested. A titanium carbide (TiC) film was patterned and treated with chlorine to obtain a TiC derived carbon (TiC-CDC) film, followed by the deposition of two types of current collectors (Ti/Au and Al) using standard micro-fabrication processes. CDC based micro-supercapacitors were electrochemically characterized by cyclic voltammetry and impedance spectroscopy using a 1 M tetraethylammonium tetrafluoroborate, NEt4BF4, in propylene carbonate (PC) electrolyte. A capacitance of 0.78 mF for the device and 1.5 mF cm-2 as the specific capacitance for the footprint of the device was measured for a 2 V potential range at 100 mV s-1. A specific energy of 3.0 mJ cm-2 and a specific power of 84 mW cm-2 were calculated for the devices. These devices provide a pathway for fabricating pure carbon-based micro-supercapacitors by micro-fabrication, and can be used for powering micro-electromechanical systems (MEMS) and electronic devices.

Unraveling the molecular mechanism of interactions of the Rho GTPases Cdc42 and Rac1 with the scaffolding protein IQGAP2.

Science.gov (United States)

Ozdemir, E Sila; Jang, Hyunbum; Gursoy, Attila; Keskin, Ozlem; Li, Zhigang; Sacks, David B; Nussinov, Ruth

2018-03-09

IQ motif-containing GTPase-activating proteins (IQGAPs) are scaffolding proteins playing central roles in cell-cell adhesion, polarity, and motility. The Rho GTPases Cdc42 and Rac1, in their GTP-bound active forms, interact with all three human IQGAPs. The IQGAP-Cdc42 interaction promotes metastasis by enhancing actin polymerization. However, despite their high sequence identity, Cdc42 and Rac1 differ in their interactions with IQGAP. Two Cdc42 molecules can bind to the Ex-domain and the RasGAP site of the GTPase-activating protein (GAP)-related domain (GRD) of IQGAP and promote IQGAP dimerization. Only one Rac1 molecule might bind to the RasGAP site of GRD and may not facilitate the dimerization, and the exact mechanism of Cdc42 and Rac1 binding to IQGAP is unclear. Using all-atom molecular dynamics simulations, site-directed mutagenesis, and Western blotting, we unraveled the detailed mechanisms of Cdc42 and Rac1 interactions with IQGAP2. We observed that Cdc42 binding to the Ex-domain of GRD of IQGAP2 (GRD2) releases the Ex-domain at the C-terminal region of GRD2, facilitating IQGAP2 dimerization. Cdc42 binding to the Ex-domain promoted allosteric changes in the RasGAP site, providing a binding site for the second Cdc42 in the RasGAP site. Of note, the Cdc42 "insert loop" was important for the interaction of the first Cdc42 with the Ex-domain. By contrast, differences in Rac1 insert-loop sequence and structure precluded its interaction with the Ex-domain. Rac1 could bind only to the RasGAP site of apo-GRD2 and could not facilitate IQGAP2 dimerization. Our detailed mechanistic insights help decipher how Cdc42 can stimulate actin polymerization in metastasis.

Ecologies of ideologies : Explaining party entry and exit in European parliaments, 1945-2013