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Sample records for features high mitotic

  1. Evaluation of associations between common variation in mitotic regulatory pathways and risk of overall and high grade breast cancer

    PubMed Central

    Stevens, Kristen N.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, V. Shane; Cerhan, James; Vachon, Celine M.; Olson, Janet E.; Couch, Fergus J.

    2012-01-01

    Mitotic regulatory pathways ensure proper timing of mitotic entry, sister chromatid cohesion and separation, and cytokinesis. Disruption of this process results in inappropriate chromosome segregation and aneuploidy and appears to contribute to cancer. Specifically, disregulation and somatic mutation of mitotic regulators has been observed in human cancers, and overexpression of mitotic regulators is common in aggressive and late stage tumors. However, the role of germline variation in mitotic pathways and risk of cancer is not well understood. We tested 1,084 haplotype-tagging and functional variants from 164 genes in mitotic regulatory pathways in 791 Caucasian women with breast cancer and 843 healthy controls for association with risk of overall and high grade breast cancer. Sixty-one single nucleotide polymorphisms (SNPs) from 40 genes were associated (p<0.05) with risk of breast cancer in a log-additive model. In addition 60 SNPs were associated (p<0.05) with risk of high grade breast cancer. However, none of these associations were significant after Bonferroni correction for multiple testing. In gene-level analyses, CDC25C, SCC1/RAD21, TLK2, and SMC6L1 were associated (p<0.05) with overall breast cancer risk, CDC6, CDC27, SUMO3, RASSF1, KIF2, and CDC14A were associated with high grade breast cancer risk, and EIF3S10 and CDC25A were associated with both. Further investigation in breast and other cancers are needed to understand the influence of inherited variation in mitotic genes on tumor grade and cancer risk. PMID:21607584

  2. Evaluation of associations between common variation in mitotic regulatory pathways and risk of overall and high grade breast cancer.

    PubMed

    Stevens, Kristen N; Wang, Xianshu; Fredericksen, Zachary; Pankratz, V Shane; Cerhan, James; Vachon, Celine M; Olson, Janet E; Couch, Fergus J

    2011-09-01

    Mitotic regulatory pathways insure proper timing of mitotic entry, sister chromatid cohesion and separation, and cytokinesis. Disruption of this process results in inappropriate chromosome segregation and aneuploidy, and appears to contribute to cancer. Specifically, disregulation and somatic mutation of mitotic regulators has been observed in human cancers, and overexpression of mitotic regulators is common in aggressive and late stage tumors. However, the role of germline variation in mitotic pathways and risk of cancer is not well understood. We tested 1,084 haplotype-tagging and functional variants from 164 genes in mitotic regulatory pathways in 791 Caucasian women with breast cancer and 843 healthy controls for association with risk of overall and high grade breast cancer. Sixty-one single nucleotide polymorphisms (SNPs) from 40 genes were associated (P<0.05) with risk of breast cancer in a log-additive model. In addition, 60 SNPs were associated (P<0.05) with risk of high grade breast cancer. However, none of these associations were significant after Bonferroni correction for multiple testing. In gene-level analyses, CDC25C, SCC1/RAD21, TLK2, and SMC6L1 were associated (P<0.05) with overall breast cancer risk, CDC6, CDC27, SUMO3, RASSF1, KIF2, and CDC14A were associated with high grade breast cancer risk, and EIF3S10 and CDC25A were associated with both. Further investigation in breast and other cancers are needed to understand the influence of inherited variation in mitotic genes on tumor grade and cancer risk. PMID:21607584

  3. Mitotic crisis

    PubMed Central

    Anantha, Rachel William; Borowiec, James A.

    2009-01-01

    Mitotic DNA damage is a constant threat to genomic integrity, yet understanding of the cellular responses to this stress remain incomplete. Recent work by Anantha et al. (PNAS 2008; 105:129038) has found surprising evidence that RPA, the primary eukaryotic single-stranded DNA-binding protein, can stimulate the ability of cells to exit mitosis into a 2N G1 phase. Along with providing additional discussion of this study, we review evidence suggesting that DNA replication and repair factors can modulate mitotic transit by acting through Polo-like kinase-1 (Plk1) and the centrosome. A crisis unmasks everyone.Mason Cooley, US aphorist. PMID:19176996

  4. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells.

    PubMed

    Mazzio, E; Badisa, R; Mack, N; Deiab, S; Soliman, K F A

    2014-06-01

    Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust National Cancer Institute botanical screenings. In this study, a high-through put microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015-0.5 mg/mL) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % of the extracts tested showed inhibitory growth (IG50 ) properties <0.0183 mg/mL. The most potent anti-mitotics (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja twigs (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu Cao [symbol: see text] Speranskia herb (Speranskia tuberculata), Bentonite clay, Bunge root (Pulsatilla chinensis), Brucea fruit (Brucea javanica), Madder root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane root (Inula Helenium), Yuan Zhi [symbol: see text] root (Polygala tenuifolia), Pagoda Tree fruit (Melia Toosendan), Stone root (Collinsonia Canadensis), and others such as American Witchhazel, Arjun, and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth root (Trillium Pendulum), and alkanet root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (S. tuberculata), which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis, leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of anti-mitotic natural plants that are effective against human breast carcinoma MDA-MB-231 cell division. PMID:24105850

  5. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells

    PubMed Central

    Mazzio, E; Badisa, R; Mack, N; Deiab, S; Soliman, KFA

    2013-01-01

    Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust NCI botanical screenings. In this study, a high-through microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015–0.5 mg/ml) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % tested showed inhibitory growth (IG50) properties <0.0183 mg/ml. The most potent anti-mitotics (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja Twigs (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu Cao Speranskia Herb (Speranskia tuberculata), Bentonite Clay, Bunge Root (Pulsatilla chinensis), Brucea Fruit (Brucea javanica), Madder Root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane Root (Inula Helenium), Yuan Zhi Root (Polygala tenuifolia), Pagoda Tree Fruit (Melia Toosendan), Stone Root (Collinsonia Canadensis) and others such as American Witchhazel, Arjun and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth-root (Trillium Pendulum) and alkanet-root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (Speranskia tuberculata) which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of natural anti-mitotic resources effective against human breast carcinoma MDA-MB-231 cell division. PMID:24105850

  6. Nup2 requires a highly divergent partner, NupA, to fulfill functions at nuclear pore complexes and the mitotic chromatin region

    PubMed Central

    Markossian, Sarine; Suresh, Subbulakshmi; Osmani, Aysha H.; Osmani, Stephen A.

    2015-01-01

    Chromatin and nuclear pore complexes (NPCs) undergo dramatic changes during mitosis, which in vertebrates and Aspergillus nidulans involves movement of Nup2 from NPCs to the chromatin region to fulfill unknown functions. This transition is shown to require the Cdk1 mitotic kinase and be promoted prematurely by ectopic expression of the NIMA kinase. Nup2 localizes with a copurifying partner termed NupA, a highly divergent yet essential NPC protein. NupA and Nup2 locate throughout the chromatin region during prophase but during anaphase move to surround segregating DNA. NupA function is shown to involve targeting Nup2 to its interphase and mitotic locations. Deletion of either Nup2 or NupA causes identical mitotic defects that initiate a spindle assembly checkpoint (SAC)–dependent mitotic delay and also cause defects in karyokinesis. These mitotic problems are not caused by overall defects in mitotic NPC disassembly–reassembly or general nuclear import. However, without Nup2 or NupA, although the SAC protein Mad1 locates to its mitotic locations, it fails to locate to NPCs normally in G1 after mitosis. Collectively the study provides new insight into the roles of Nup2 and NupA during mitosis and in a surveillance mechanism that regulates nucleokinesis when mitotic defects occur after SAC fulfillment. PMID:25540430

  7. Toward automatic mitotic cell detection and segmentation in multispectral histopathological images.

    PubMed

    Lu, Cheng; Mandal, Mrinal

    2014-03-01

    The count of mitotic cells is a critical factor in most cancer grading systems. Extracting the mitotic cell from the histopathological image is a very challenging task. In this paper, we propose an efficient technique for detecting and segmenting the mitotic cells in the high-resolution multispectral image. The proposed technique consists of three main modules: discriminative image generation, mitotic cell candidate detection and segmentation, and mitotic cell candidate classification. In the first module, a discriminative image is obtained by linear discriminant analysis using ten different spectral band images. A set of mitotic cell candidate regions is then detected and segmented by the Bayesian modeling and local-region threshold method. In the third module, a 226 dimension feature is extracted from the mitotic cell candidates and their surrounding regions. An imbalanced classification framework is then applied to perform the classification for the mitotic cell candidates in order to detect the real mitotic cells. The proposed technique has been evaluated on a publicly available dataset of 35 10 multispectral images, in which 224 mitotic cells are manually labeled by experts. The proposed technique is able to provide superior performance compared to the existing technique, 81.5% sensitivity rate and 33.9% precision rate in terms of detection performance, and 89.3% sensitivity rate and 87.5% precision rate in terms of segmentation performance. PMID:24608059

  8. Leiomyosarcoma arising in a patient with prior mitotically active leiomyoma.

    PubMed

    Kim, Jin Hwi; Choi, Young Jin; Kim, Dong Chul; Lee, Sung Jong

    2010-02-01

    Mitotically active leiomyomas exhibiting insignificant cytologic atypia (none to mild) with an increased mitotic count of 5-20 mitotic figures per 10 high power fields, and without coagulative tumor cell necrosis or atypical mitoses, tend to have a benign clinical course. We encountered a case of a mitotically active leiomyoma and malignant transformation after a total hysterectomy. The recurrent multiple abdominal masses were removed surgically; most of them were benign leiomyomas, but some were leiomyosarcomas. Although most mitotically active leiomyomas have a benign clinical course, these lesions can recur and have the potential for malignant transformation. Therefore, patients with mitotically active leiomyomas require close follow-up. PMID:20178549

  9. Iterative feature removal yields highly discriminative pathways

    PubMed Central

    2013-01-01

    Background We introduce Iterative Feature Removal (IFR) as an unbiased approach for selecting features with diagnostic capacity from large data sets. The algorithm is based on recently developed tools in machine learning that are driven by sparse feature selection goals. When applied to genomic data, our method is designed to identify genes that can provide deeper insight into complex interactions while remaining directly connected to diagnostic utility. We contrast this approach with the search for a minimal best set of discriminative genes, which can provide only an incomplete picture of the biological complexity. Results Microarray data sets typically contain far more features (genes) than samples. For this type of data, we demonstrate that there are many equivalently-predictive subsets of genes. We iteratively train a classifier using features identified via a sparse support vector machine. At each iteration, we remove all the features that were previously selected. We found that we could iterate many times before a sustained drop in accuracy occurs, with each iteration removing approximately 30 genes from consideration. The classification accuracy on test data remains essentially flat even as hundreds of top-genes are removed. Our method identifies sets of genes that are highly predictive, even when comprised of genes that individually are not. Through automated and manual analysis of the selected genes, we demonstrate that the selected features expose relevant pathways that other approaches would have missed. Conclusions Our results challenge the paradigm of using feature selection techniques to design parsimonious classifiers from microarray and similar high-dimensional, small-sample-size data sets. The fact that there are many subsets of genes that work equally well to classify the data provides a strong counter-result to the notion that there is a small number of top genes that should be used to build classifiers. In our results, the best classifiers were formed using genes with limited univariate power, thus illustrating that deeper mining of features using multivariate techniques is important. PMID:24274115

  10. A Non-Motor Microtubule Binding Site Is Essential for the High Processivity and Mitotic Function of Kinesin-8 Kif18A

    PubMed Central

    Howard, Jonathon; Mayer, Thomas U.

    2011-01-01

    Background Members of the kinesin-8 subfamily are plus end-directed molecular motors that accumulate at the plus-ends of kinetochore-microtubules (kt-MTs) where they regulate MT dynamics. Loss of vertebrate kinesin-8 function induces hyperstable MTs and elongated mitotic spindles accompanied by severe chromosome congression defects. It has been reported that the motility of human kinesin-8, Kif18A, is required for its accumulation at the plus tips of kt-MTs. Methodology/Findings Here, we investigate how Kif18A localizes to the plus-ends of kt-MTs. We find that Kif18A lacking its C-terminus does not accumulate on the tips of kt-MTs and fails to fulfill its mitotic function. In vitro studies reveal that Kif18A possesses a non-motor MT binding site located within its C-proximal 121 residues. Using single molecule measurements we find that Kif18A is a highly processive motor and, furthermore, that the C-terminal tail is essential for the high processivity of Kif18A. Conclusion/Significance These results show that Kif18A like its yeast orthologue is a highly processive motor. The ability of Kif18A to walk on MTs for a long distance without dissociating depends on a non-motor MT binding site located at the C-terminus of Kif18A. This C-proximal tail of Kif18A is essential for its plus-end accumulation and mitotic function. These findings advance our understanding of how Kif18A accumulates at the tips of kt-MTs to fulfill its function in mitosis. PMID:22102900

  11. Building mitotic chromosomes

    PubMed Central

    Ohta, Shinya; Wood, Laura; Bukowski-Wills, Jimi-Carlo; Rappsilber, Juri; Earnshaw, William C

    2011-01-01

    Mitotic chromosomes are the iconic structures into which the genome is packaged to ensure its accurate segregation during mitosis. Although they have appeared on countless journal cover illustrations, there remains no consensus on how the chromatin fiber is packaged during mitosis. In fact, work in recent years has both added to existing controversies and sparked new ones. By contrast, there has been very significant progress in determining the protein composition of isolated mitotic chromosomes. Here, we discuss recent studies of chromosome organization and provide an in depth description of the latest proteomics studies, which have at last provided us with a definitive proteome for vertebrate chromosomes. PMID:20974528

  12. A High Throughput, Whole Cell Screen for Small Molecule Inhibitors of the Mitotic Spindle Checkpoint Identifies OM137, a Novel Aurora Kinase Inhibitor

    PubMed Central

    DeMoe, Joanna H.; Santaguida, Stefano; Daum, John R.; Musacchio, Andrea; Gorbsky, Gary J.

    2008-01-01

    In mitosis the kinetochores of chromosomes that lack full microtubule attachments and/or mechanical tension activate a signaling pathway called the mitotic spindle checkpoint that blocks progression into anaphase and prevents premature segregation of the chromatids until chromosomes become aligned at the metaphase plate (1). The spindle checkpoint is responsible for arresting cells in mitosis in response to chemotherapeutic spindle poisons such as paclitaxel or vinblastine. Some cancer cells show a weakened checkpoint signaling system that may contribute to chromosome instability in tumors. Since complete absence of the spindle checkpoint leads to catastrophic cell division, we reasoned that drugs targeting the checkpoint might provide a therapeutic window in which the checkpoint would be eliminated in cancer cells but sufficiently preserved in normal cells. We developed an assay to identify lead compounds that inhibit the spindle checkpoint. Most cells respond to microtubule drugs by activating the spindle checkpoint and arresting in mitosis with a rounded morphology. Our assay depended on the ability of checkpoint inhibitor compounds to drive mitotic exit and cause cells to flatten onto the substrate in the continuous presence of microtubule drugs. In this study we characterize one of the compounds, OM137, as an inhibitor of Aurora kinases. We find that this compound is growth inhibitory to cultured cells when applied at high concentration and potentiates the growth inhibitory effects of subnanomolar concentrations of paclitaxel. PMID:19190331

  13. Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

    PubMed Central

    Aziz, Sura; Wik, Elisabeth; Davidsen, Benedicte; Aas, Hans; Aas, Turid; Akslen, Lars A.

    2016-01-01

    Few studies have addressed the risk of recurrence by assessing proliferation markers in lymph node metastasis from breast cancer. Here, we aimed to examine Ki-67 expression and mitotic count in lymph nodes in comparison with primary tumors. A cohort of node positive breast cancer (n = 168) was studied as a part of the prospective Norwegian Breast Cancer Screening Program (1996–2009). The percentage of Ki-67 positivity was counted per 500 tumor cells in hot-spot areas (x630). Mitotic count was conducted in the most cellular and mitotic active areas in 10 high power fields (x400). Our results showed that Ki-67 and mitotic count were significantly correlated between primary tumor and lymph nodes (Spearman`s correlation 0. 56 and 0.46, respectively) and were associated with most of the histologic features of the primary tumor. Univariate survival analysis (log-rank test) showed that high Ki-67 and mitotic count in the primary tumor and lymph node metastasis significantly predicted risk of recurrence. In multivariate analysis, mitotic count in the lymph node metastasis was an independent predictor of tumor recurrence. In conclusion, proliferation markers in lymph node metastases significantly predicted disease free survival in node positive breast cancer. PMID:26954367

  14. Sources and structures of mitotic crossovers that arise when BLM helicase is absent in Drosophila.

    PubMed

    LaFave, Matthew C; Andersen, Sabrina L; Stoffregen, Eric P; Holsclaw, Julie K; Kohl, Kathryn P; Overton, Lewis J; Sekelsky, Jeff

    2014-01-01

    The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions that block replication forks increased crossover frequencies, consistent with functions for BLM in responding to fork blockage. In contrast, treatment with hydroxyurea, which stalls forks, did not elevate crossovers, even though mutants lacking BLM are sensitive to killing by this agent. To learn about sources of spontaneous recombination, we mapped mitotic crossovers in mutants lacking BLM. In the male germline, irradiation-induced crossovers were distributed randomly across the euchromatin, but spontaneous crossovers were nonrandom. We suggest that regions of the genome with a high frequency of mitotic crossovers may be analogous to common fragile sites in the human genome. Interestingly, in the male germline there is a paucity of crossovers in the interval that spans the pericentric heterochromatin, but in the female germline this interval is more prone to crossing over. Finally, our system allowed us to recover pairs of reciprocal crossover chromosomes. Sequencing of these revealed the existence of gene conversion tracts and did not provide any evidence for mutations associated with crossovers. These findings provide important new insights into sources and structures of mitotic crossovers and functions of BLM helicase. PMID:24172129

  15. The ATPase cycle of the mitotic motor CENP-E.

    PubMed

    Rosenfeld, Steven S; van Duffelen, Marilyn; Behnke-Parks, William M; Beadle, Christopher; Corrreia, John; Xing, Jun

    2009-11-20

    We have previously shown that the mitotic motor centrosome protein E (CENP-E) is capable of walking for more than 250 steps on its microtubule track without dissociating. We have examined the kinetics of this molecular motor to see if its enzymology explains this remarkable degree of processivity. We find that like the highly processive transport motor kinesin 1, the enzymatic cycle of CENP-E is characterized by rapid ATP binding, multiple enzymatic turnovers per diffusive encounter, and gating of nucleotide binding. These features endow CENP-E with a high duty cycle, a prerequisite for processivity. However, unlike kinesin 1, neck linker docking in CENP-E is slow, occurring at a rate closer to that for Eg5, a mitotic kinesin that takes only 5-10 steps per processive run. These results suggest that like kinesin 1, features outside of the catalytic domain of CENP-E may also play a role in regulating the processive behavior of this motor. PMID:19759394

  16. Mitotic chromosome condensation in vertebrates

    SciTech Connect

    Vagnarelli, Paola

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes of proteins and their co-operation in establishing the final mitotic chromosome structure.

  17. High frequency, cell type-specific visualization of fluorescent-tagged genomic sites in interphase and mitotic cells of living Arabidopsis plants

    PubMed Central

    2010-01-01

    Background Interphase chromosome organization and dynamics can be studied in living cells using fluorescent tagging techniques that exploit bacterial operator/repressor systems and auto-fluorescent proteins. A nuclear-localized Repressor Protein-Fluorescent Protein (RP-FP) fusion protein binds to operator repeats integrated as transgene arrays at defined locations in the genome. Under a fluorescence microscope, the tagged sites appear as bright fluorescent dots in living cells. This technique has been used successfully in plants, but is often hampered by low expression of genes encoding RP-FP fusion proteins, perhaps owing to one or more gene silencing mechanisms that are prevalent in plant cells. Results We used two approaches to overcome this problem. First, we tested mutations in four factors involved in different types of gene silencing and/or epigenetic modifications for their effects on nuclear fluorescence. Only mutations in DDM1, a chromatin remodelling ATPase involved in repeat-induced heterochromatin formation and DNA methylation, released silencing of the RP-FP fusion protein. This result suggested that the operator repeats can trigger silencing of the adjacent gene encoding the RP-FP fusion protein. In the second approach, we transformed the tagged lines with a second T-DNA encoding the RP-FP fusion protein but lacking operator repeats. This strategy avoided operator repeat-induced gene silencing and increased the number of interphase nuclei displaying fluorescent dots. In a further extension of the technique, we show that green fluorescent-tagged sites can be visualized on moving mitotic chromosomes stained with red fluorescent-labelled histone H2B. Conclusions The results illustrate the propensity of operator repeat arrays to form heterochromatin that can silence the neighbouring gene encoding the RP-FP fusion protein. Supplying the RP-FP fusion protein in trans from a second T-DNA largely alleviates this problem. Depending on the promoter used to drive expression of the RP-FP fusion protein gene, the fluorescent tagged sites can be visualized at high frequency in different cell types. The ability to observe fluorescent dots on both interphase and mitotic chromosomes allows tagged sites to be tracked throughout the cell cycle. These improvements enhance the versatility of the fluorescent tagging technique for future studies of chromosome arrangement and dynamics in living plants. PMID:20148117

  18. Chemically diverse microtubule stabilizing agents initiate distinct mitotic defects and dysregulated expression of key mitotic kinases.

    PubMed

    Rohena, Cristina C; Peng, Jiangnan; Johnson, Tyler A; Crews, Phillip; Mooberry, Susan L

    2013-04-15

    Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent than paclitaxel or laulimalide, which is consistent with the distinct defects in expression and activation of Plk1 and Eg5 caused by each stabilizer. Localization studies revealed that TPX2 and Aurora A are associated with each spindle aster formed by each stabilizer. This suggests a common mechanism of aster formation. However, taccalonolide AJ also causes pericentrin accumulation on every spindle aster. The presence of pericentrin at every spindle aster initiated by taccalonolide AJ might facilitate the maintenance and stability of the highly focused asters formed by this stabilizer. Laulimalide and paclitaxel cause completely different patterns of expression and activation of these proteins, as well as phenotypically different spindle phenotypes. Delineating how diverse microtubule stabilizers affect mitotic signaling pathways could identify key proteins involved in modulating sensitivity and resistance to the antimitotic actions of these compounds. PMID:23399639

  19. Monoclonal antibodies to mitotic cells.

    PubMed Central

    Davis, F M; Tsao, T Y; Fowler, S K; Rao, P N

    1983-01-01

    Certain proteins or activities are present in mitotic cells but not in interphase cells. These proteins may be synthesized or activated, or both, just prior to mitosis and are responsible for the breakdown of the nuclear envelope and the condensation of chromosomes. To learn more about the nature of these proteins, we raised monoclonal antibodies to mitotic cells. Spleen cells from mice immunized with a 0.15 M NaCl extract of synchronized mitotic HeLa cells were fused with SP2/0-Ag14 mouse myeloma cells, and hybrids were selected in medium containing hypoxanthine, methotrexate, thymidine, and glycine. Two different hybridoma clones secreting antibodies reactive with mitotic and meiotic cells from every species tested were isolated. Chromosomes as well as cytoplasm in mitotic cells reacted with the antibodies, as detected by indirect immunofluorescence. The proteins from mitotic cells were separated by electrophoresis in NaDodSO4/polyacrylamide slab gels, transferred to nitrocellulose sheets, and stained immunochemically. The two antibodies, designated MPM-1 and MPM-2, recognize a family of polypeptides with apparent molecular masses of 0.40 to greater than 200 kilodaltons (kDa). Both antibodies reacted strongly with three polypeptide bands of 182 kDa, 118 kDa, and 70 kDa. Only mitotic cells exhibited the protein bands that were recognized by the antibodies. All these bands were found to be phosphoproteins as shown by 32P labeling and autoradiography and their removal by alkaline phosphatase treatment. Images PMID:6574461

  20. Wee-1 kinase inhibition overcomes cisplatin resistance associated with high-risk TP53 mutations in head and neck cancer through mitotic arrest followed by senescence.

    PubMed

    Osman, Abdullah A; Monroe, Marcus M; Ortega Alves, Marcus V; Patel, Ameeta A; Katsonis, Panagiotis; Fitzgerald, Alison L; Neskey, David M; Frederick, Mitchell J; Woo, Sang Hyeok; Caulin, Carlos; Hsu, Teng-Kuei; McDonald, Thomas O; Kimmel, Marek; Meyn, Raymond E; Lichtarge, Olivier; Myers, Jeffrey N

    2015-02-01

    Although cisplatin has played a role in "standard-of-care" multimodality therapy for patients with advanced squamous cell carcinoma of the head and neck (HNSCC), the rate of treatment failure remains particularly high for patients receiving cisplatin whose tumors have mutations in the TP53 gene. We found that cisplatin treatment of HNSCC cells with mutant TP53 leads to arrest of cells in the G2 phase of the cell cycle, leading us to hypothesize that the wee-1 kinase inhibitor MK-1775 would abrogate the cisplatin-induced G2 block and thereby sensitize isogenic HNSCC cells with mutant TP53 or lacking p53 expression to cisplatin. We tested this hypothesis using clonogenic survival assays, flow cytometry, and in vivo tumor growth delay experiments with an orthotopic nude mouse model of oral tongue cancer. We also used a novel TP53 mutation classification scheme to identify which TP53 mutations are associated with limited tumor responses to cisplatin treatment. Clonogenic survival analyses indicate that nanomolar concentration of MK-1775 sensitizes HNSCC cells with high-risk mutant p53 to cisplatin. Consistent with its ability to chemosensitize, MK-1775 abrogated the cisplatin-induced G2 block in p53-defective cells leading to mitotic arrest associated with a senescence-like phenotype. Furthermore, MK-1775 enhanced the efficacy of cisplatin in vivo in tumors harboring TP53 mutations. These results indicate that HNSCC cells expressing high-risk p53 mutations are significantly sensitized to cisplatin therapy by the selective wee-1 kinase inhibitor, supporting the clinical evaluation of MK-1775 in combination with cisplatin for the treatment of patients with TP53 mutant HNSCC. PMID:25504633

  1. Wee-1 Kinase Inhibition Overcomes Cisplatin Resistance Associated with High-Risk TP53 Mutations in Head and Neck Cancer through Mitotic Arrest Followed by Senescence

    PubMed Central

    Osman, Abdullah A.; Monroe, Marcus M.; Ortega Alves, Marcus V.; Patel, Ameeta A.; Katsonis, Panagiotis; Fitzgerald, Alison L.; Neskey, David M.; Frederick, Mitchell J.; Woo, Sang Hyeok; Caulin, Carlos; Hsu, Teng-Kuei; McDonald, Thomas O.; Kimmel, Marek; Meyn, Raymond E.; Lichtarge, Olivier; Myers, Jeffrey N.

    2015-01-01

    Although cisplatin has played a role in standard-of-care multimodality therapy for patients with advanced squamous cell carcinoma of the head and neck (HNSCC), the rate of treatment failure remains particularly high for patients receiving cisplatin whose tumors have mutations in the TP53 gene. We found that cisplatin treatment of HNSCC cells with mutant TP53 leads to arrest of cells in the G2 phase of the cell cycle, leading us to hypothesize that the wee-1 kinase inhibitor MK-1775 would abrogate the cisplatin-induced G2 block and thereby sensitize isogenic HNSCC cells with mutant TP53 or lacking p53 expression to cisplatin. We tested this hypothesis using clonogenic survival assays, flow cytometry, and in vivo tumor growth delay experiments with an orthotopic nude mouse model of oral tongue cancer. We also used a novel TP53 mutation classification scheme to identify which TP53 mutations are associated with limited tumor responses to cisplatin treatment. Clonogenic survival analyses indicate that nanomolar concentration of MK-1775 sensitizes HNSCC cells with high-risk mutant p53 to cisplatin. Consistent with its ability to chemosensitize, MK-1775 abrogated the cisplatin-induced G2 block in p53-defective cells leading to mitotic arrest associated with a senescence-like phenotype. Furthermore, MK-1775 enhanced the efficacy of cisplatin in vivo in tumors harboring TP53 mutations. These results indicate that HNSCC cells expressing high-risk p53 mutations are significantly sensitized to cisplatin therapy by the selective wee-1 kinase inhibitor, supporting the clinical evaluation of MK-1775 in combination with cisplatin for the treatment of patients with TP53 mutant HNSCC. PMID:25504633

  2. Isolation of Human Mitotic Protein Phosphatase Complexes: Identification of a Complex between Protein Phosphatase 1 and the RNA Helicase Ddx21

    PubMed Central

    De Wever, Veerle; Lloyd, David C.; Nasa, Isha; Nimick, Mhairi; Trinkle-Mulcahy, Laura; Gourlay, Robert; Morrice, Nick; Moorhead, Greg B. G.

    2012-01-01

    Metazoan mitosis requires remodelling of sub-cellular structures to ensure proper division of cellular and genetic material. Faults often lead to genomic instability, cell cycle arrests and disease onset. These key structural changes are under tight spatial-temporal and post-translational control, with crucial roles for reversible protein phosphorylation. The phosphoprotein phosphatases PP1 and PP2A are paramount for the timely execution of mitotic entry and exit but their interaction partners and substrates are still largely unresolved. High throughput, mass-spectrometry based studies have limited sensitivity for the detection of low-abundance and transient complexes, a typical feature of many protein phosphatase complexes. Moreover, the limited timeframe during which mitosis takes place reduces the likelihood of identifying mitotic phosphatase complexes in asynchronous cells. Hence, numerous mitotic protein phosphatase complexes still await identification. Here we present a strategy to enrich and identify serine/threonine protein phosphatase complexes at the mitotic spindle. We thus identified a nucleolar RNA helicase, Ddx21/Gu, as a novel, direct PP1 interactor. Furthermore, our results place PP1 within the toposome, a Topoisomerase II alpha (TOPOII?) containing complex with a key role in mitotic chromatin regulation and cell cycle progression, possibly via regulated protein phosphorylation. This study provides a strategy for the identification of further mitotic PP1 partners and the unravelling of PP1 functions during mitosis. PMID:22761809

  3. Mitotic Spindle Form and Function

    PubMed Central

    Winey, Mark; Bloom, Kerry

    2012-01-01

    The Saccharomyces cerevisiae mitotic spindle in budding yeast is exemplified by its simplicity and elegance. Microtubules are nucleated from a crystalline array of proteins organized in the nuclear envelope, known as the spindle pole body in yeast (analogous to the centrosome in larger eukaryotes). The spindle has two classes of nuclear microtubules: kinetochore microtubules and interpolar microtubules. One kinetochore microtubule attaches to a single centromere on each chromosome, while approximately four interpolar microtubules emanate from each pole and interdigitate with interpolar microtubules from the opposite spindle to provide stability to the bipolar spindle. On the cytoplasmic face, two to three microtubules extend from the spindle pole toward the cell cortex. Processes requiring microtubule function are limited to spindles in mitosis and to spindle orientation and nuclear positioning in the cytoplasm. Microtubule function is regulated in large part via products of the 6 kinesin gene family and the 1 cytoplasmic dynein gene. A single bipolar kinesin (Cin8, class Kin-5), together with a depolymerase (Kip3, class Kin-8) or minus-end-directed kinesin (Kar3, class Kin-14), can support spindle function and cell viability. The remarkable feature of yeast cells is that they can survive with microtubules and genes for just two motor proteins, thus providing an unparalleled system to dissect microtubule and motor function within the spindle machine. PMID:22491889

  4. Energy Conservation Featured in Illinois High School

    ERIC Educational Resources Information Center

    Modern Schools, 1976

    1976-01-01

    The William Fremd High School in Palatine, Illinois, scheduled to open in 1977, is being built with energy conservation uppermost in mind. In this system, 70 heat pumps will heat and cool 300,000 square feet of educational facilities. (Author/MLF)

  5. Mitotic Exit Control as an Evolved Complex System

    SciTech Connect

    Bosl, W; Li, R

    2005-04-25

    The exit from mitosis is the last critical decision a cell has to make during a division cycle. A complex regulatory system has evolved to evaluate the success of mitotic events and control this decision. Whereas outstanding genetic work in yeast has led to rapid discovery of a large number of interacting genes involved in the control of mitotic exit, it has also become increasingly difficult to comprehend the logic and mechanistic features embedded in the complex molecular network. Our view is that this difficulty stems in part from the attempt to explain mitotic exit control using concepts from traditional top-down engineering design, and that exciting new results from evolutionary engineering design applied to networks and electronic circuits may lend better insights. We focus on four particularly intriguing features of the mitotic exit control system: the two-stepped release of Cdc14; the self-activating nature of Tem1 GTPase; the spatial sensor associated with the spindle pole body; and the extensive redundancy in the mitotic exit network. We attempt to examine these design features from the perspective of evolutionary design and complex system engineering.

  6. Quantitative Comparison of Mitotic Spindles by Confocal Image Analysis

    SciTech Connect

    Price, Jeffery R; Aykac, Deniz; Gleason, Shaun Scott

    2005-01-01

    The mitotic spindle is a subcellular protein structure that facilitates chromosome segregation and is crucial to cell division. We describe an image processing approach to quantitatively characterize and compare mitotic spindles that have been imaged three dimensionally using confocal microscopy with fixed-cell preparations. The proposed approach is based on a set of features that are computed from each image stack representing a spindle. We compare several spindle datasets of varying biological (genotype) and/or environmental (drug treatment) conditions. The goal of this effort is to aid biologists in detecting differences between spindles that may not be apparent under subjective visual inspection, and furthermore, to eventually automate such analysis in high-throughput scenarios (thousands of images) where manual inspection would be unreasonable. Experimental results on positive- and negative-control data indicate that the proposed approach is indeed effective. Differences are detected when it is known they do exist (positive control) and no differences are detected when there are none (negative control). In two other experimental comparisons, results indicate structural spindle differences that biologists had not observed previously.

  7. High-resolution Urban Image Classification Using Extended Features

    SciTech Connect

    Vatsavai, Raju

    2011-01-01

    High-resolution image classification poses several challenges because the typical object size is much larger than the pixel resolution. Any given pixel (spectral features at that location) by itself is not a good indicator of the object it belongs to without looking at the broader spatial footprint. Therefore most modern machine learning approaches that are based on per-pixel spectral features are not very effective in high- resolution urban image classification. One way to overcome this problem is to extract features that exploit spatial contextual information. In this study, we evaluated several features in- cluding edge density, texture, and morphology. Several machine learning schemes were tested on the features extracted from a very high-resolution remote sensing image and results were presented.

  8. Measuring mitotic spindle dynamics in budding yeast

    NASA Astrophysics Data System (ADS)

    Plumb, Kemp

    In order to carry out its life cycle and produce viable progeny through cell division, a cell must successfully coordinate and execute a number of complex processes with high fidelity, in an environment dominated by thermal noise. One important example of such a process is the assembly and positioning of the mitotic spindle prior to chromosome segregation. The mitotic spindle is a modular structure composed of two spindle pole bodies, separated in space and spanned by filamentous proteins called microtubules, along which the genetic material of the cell is held. The spindle is responsible for alignment and subsequent segregation of chromosomes into two equal parts; proper spindle positioning and timing ensure that genetic material is appropriately divided amongst mother and daughter cells. In this thesis, I describe fluorescence confocal microscopy and automated image analysis algorithms, which I have used to observe and analyze the real space dynamics of the mitotic spindle in budding yeast. The software can locate structures in three spatial dimensions and track their movement in time. By selecting fluorescent proteins which specifically label the spindle poles and cell periphery, mitotic spindle dynamics have been measured in a coordinate system relevant to the cell division. I describe how I have characterised the accuracy and precision of the algorithms by simulating fluorescence data for both spindle poles and the budding yeast cell surface. In this thesis I also describe the construction of a microfluidic apparatus that allows for the measurement of long time-scale dynamics of individual cells and the development of a cell population. The tools developed in this thesis work will facilitate in-depth quantitative analysis of the non-equilibrium processes in living cells.

  9. Micromechanics of human mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Sun, Mingxuan; Kawamura, Ryo; Marko, John F.

    2011-02-01

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed.

  10. Unsupervised Feature Learning for High-Resolution Satellite Image Classification

    SciTech Connect

    Cheriyadat, Anil M

    2013-01-01

    The rich data provided by high-resolution satellite imagery allow us to directly model geospatial neighborhoods by understanding their spatial and structural patterns. In this paper we explore an unsupervised feature learning approach to model geospatial neighborhoods for classification purposes. While pixel and object based classification approaches are widely used for satellite image analysis, often these approaches exploit the high-fidelity image data in a limited way. In this paper we extract low-level features to characterize the local neighborhood patterns. We exploit the unlabeled feature measurements in a novel way to learn a set of basis functions to derive new features. The derived sparse feature representation obtained by encoding the measured features in terms of the learned basis function set yields superior classification performance. We applied our technique on two challenging image datasets: ORNL dataset representing one-meter spatial resolution satellite imagery representing five land-use categories and, UCMERCED dataset consisting of 21 different categories representing sub-meter resolution overhead imagery. Our results are highly promising and, in the case of UCMERCED dataset we outperform the best results obtained for this dataset. We show that our feature extraction and learning methods are highly effective in developing a detection system that can be used to automatically scan large-scale high-resolution satellite imagery for detecting large-facility.

  11. The Prognostic Role of Mitotic Index in Hepatocellular Carcinoma Patients after Curative Hepatectomy

    PubMed Central

    Ha, Sang Yun; Choi, Misun; Lee, Taebum; Park, Cheol-Keun

    2016-01-01

    Purpose High proliferation rate is a hallmark of cancer. The mitotic index is a useful and simple method for analysis of cell proliferation. However, the practical utility of mitotic index as a predictor of prognosis in patients with hepatocellular carcinoma (HCC) has not been determined. Therefore, we examined mitotic index as a prognostic marker in HCC patients. Materials and Methods We counted the number of mitotic cells in 10 high-power fields of the tumor area on hematoxylin and eosinstained slides representing 282 surgically resected HCCs. The highest number of mitotic cells was defined as the mitotic index. Results High mitotic index was observed in 127 of 282 HCCs. High mitotic index showed significant association with younger age, larger tumor size, higher Edmondson grade, microvascular invasion, major portal vein invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T-stage, higher Barcelona Clinic Liver Cancer (BCLC) stage, higher alpha-fetoprotein level, hepatitis B virus etiology, and liver cirrhosis. Patients with high mitotic index had shorter disease-specific survival (DSS) (p < 0.001) and tended to have shorter recurrence-free survival (p=0.112). In subgroup analysis among patients with a larger tumor size, microvascular invasion, intrahepatic metastasis, higher AJCC T-stage, and higher BLCL stage, high mitotic index showed unfavorable influences on DSS (p=0.001, p=0.008, p=0.003, p=0.012, and p < 0.001, respectively). In addition, high mitotic index was an independent predictor of shorter DSS (p=0.004). Conclusion High mitotic index may be a novel predictor of DSS in patients with HCC and may have utility as an auxiliary prognostic factor in HCC. PMID:25797572

  12. High Dimensional Classification Using Features Annealed Independence Rules.

    PubMed

    Fan, Jianqing; Fan, Yingying

    2008-01-01

    Classification using high-dimensional features arises frequently in many contemporary statistical studies such as tumor classification using microarray or other high-throughput data. The impact of dimensionality on classifications is largely poorly understood. In a seminal paper, Bickel and Levina (2004) show that the Fisher discriminant performs poorly due to diverging spectra and they propose to use the independence rule to overcome the problem. We first demonstrate that even for the independence classification rule, classification using all the features can be as bad as the random guessing due to noise accumulation in estimating population centroids in high-dimensional feature space. In fact, we demonstrate further that almost all linear discriminants can perform as bad as the random guessing. Thus, it is paramountly important to select a subset of important features for high-dimensional classification, resulting in Features Annealed Independence Rules (FAIR). The conditions under which all the important features can be selected by the two-sample t-statistic are established. The choice of the optimal number of features, or equivalently, the threshold value of the test statistics are proposed based on an upper bound of the classification error. Simulation studies and real data analysis support our theoretical results and demonstrate convincingly the advantage of our new classification procedure. PMID:19169416

  13. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1.

    PubMed

    Aarts, Marieke; Sharpe, Rachel; Garcia-Murillas, Isaac; Gevensleben, Heidrun; Hurd, Melissa S; Shumway, Stuart D; Toniatti, Carlo; Ashworth, Alan; Turner, Nicholas C

    2012-06-01

    Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. We show that WEE1 inhibition forces S-phase-arrested cells directly into mitosis without completing DNA synthesis, resulting in highly abnormal mitoses characterized by dispersed chromosomes and disorganized bipolar spindles, ultimately resulting in mitotic exit with gross micronuclei formation and apoptosis. This mechanism of cell death is shared by CHK1 inhibitors, and combined WEE1 and CHK1 inhibition forces mitotic entry from S-phase in the absence of chemotherapy. We show that p53/p21 inactivation combined with high expression of mitotic cyclins and EZH2 predispose to mitotic entry during S-phase with cells reliant on WEE1 to prevent premature cyclin-dependent kinase (CDK)1 activation. These features are characteristic of aggressive breast, and other, cancers for which WEE1 inhibitor combinations represent a promising targeted therapy. PMID:22628408

  14. Exploring KM Features of High-Performance Companies

    NASA Astrophysics Data System (ADS)

    Wu, Wei-Wen

    2007-12-01

    For reacting to an increasingly rival business environment, many companies emphasize the importance of knowledge management (KM). It is a favorable way to explore and learn KM features of high-performance companies. However, finding out the critical KM features of high-performance companies is a qualitative analysis problem. To handle this kind of problem, the rough set approach is suitable because it is based on data-mining techniques to discover knowledge without rigorous statistical assumptions. Thus, this paper explored KM features of high-performance companies by using the rough set approach. The results show that high-performance companies stress the importance on both tacit and explicit knowledge, and consider that incentives and evaluations are the essentials to implementing KM.

  15. The Sparse MLE for Ultra-High-Dimensional Feature Screening

    PubMed Central

    Xu, Chen; Chen, Jiahua

    2014-01-01

    Feature selection is fundamental for modeling the high dimensional data, where the number of features can be huge and much larger than the sample size. Since the feature space is so large, many traditional procedures become numerically infeasible. It is hence essential to first remove most apparently non-influential features before any elaborative analysis. Recently, several procedures have been developed for this purpose, which include the sure-independent-screening (SIS) as a widely-used technique. To gain the computational efficiency, the SIS screens features based on their individual predicting power. In this paper, we propose a new screening method via the sparsity-restricted maximum likelihood estimator (SMLE). The new method naturally takes the joint effects of features in the screening process, which gives itself an edge to potentially outperform the existing methods. This conjecture is further supported by the simulation studies under a number of modeling settings. We show that the proposed method is screening consistent in the context of ultra-high-dimensional generalized linear models. PMID:25382886

  16. Mitotic Kinases and p53 Signaling

    PubMed Central

    Ha, Geun-Hyoung; Breuer, Eun-Kyoung Yim

    2012-01-01

    Mitosis is tightly regulated and any errors in this process often lead to aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic kinases is significantly associated with improper cell division and aneuploidy. Because of their importance during mitosis and the relevance to cancer, mitotic kinase signaling has been extensively studied over the past few decades and, as a result, several mitotic kinase inhibitors have been developed. Despite promising preclinical results, targeting mitotic kinases for cancer therapy faces numerous challenges, including safety and patient selection issues. Therefore, there is an urgent need to better understand the molecular mechanisms underlying mitotic kinase signaling and its interactive network. Increasing evidence suggests that tumor suppressor p53 functions at the center of the mitotic kinase signaling network. In response to mitotic spindle damage, multiple mitotic kinases phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53 can also regulate the expression and function of mitotic kinases, suggesting the existence of a network of mutual regulation, which can be positive or negative, between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory network will provide knowledge to overcome current limitations of targeting mitotic kinases and further improve the results of targeted therapy. PMID:22852086

  17. Origin of the high vlos feature in the Galactic bar

    NASA Astrophysics Data System (ADS)

    Aumer, Michael; Schönrich, Ralph

    2015-12-01

    We analyse a controlled N-body+smoothed particle hydrodynamics simulation of a growing disc galaxy within a non-growing, live dark halo. The disc is continuously fed with gas and star particles on near-circular orbits and develops a bar comparable in size to the one of the Milky Way (MW). We extract line-of-sight velocity vlos distributions from the model and compare it to data recently obtained from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey which show distinct high-velocity features around vlos ˜ 200 km s-1. With an APOGEE-like selection function, but without any scaling nor adjustment, we find vlos distributions very similar to those in APOGEE. The stars that make up the high vlos features at positive longitudes l are preferentially young bar stars (age τ ≲ 2-3 Gyr) which move away from us along the rear side of the bar. At negative l, we find the corresponding low vlos feature from stars moving towards us. At l > 10 deg, the highest vlos stars are a mixture of bar and background disc stars which complicates the interpretation of observations. The main peak in vlos is dominated by fore- and background stars. At a given time, ˜40-50 per cent of high vlos stars occupy x1-like orbits, but a significant fraction are on more complex orbits. The observed feature is likely due to a population of dynamically cool, young stars formed from gas just outside the bar and subsequently captured by the growing bar. The high vlos features disappear at high latitudes |b| ≳ 2 deg which explains the non-detection of such features in other surveys.

  18. Spectral feature design in high dimensional multispectral data

    NASA Technical Reports Server (NTRS)

    Chen, Chih-Chien Thomas; Landgrebe, David A.

    1988-01-01

    The High resolution Imaging Spectrometer (HIRIS) is designed to acquire images simultaneously in 192 spectral bands in the 0.4 to 2.5 micrometers wavelength region. It will make possible the collection of essentially continuous reflectance spectra at a spectral resolution sufficient to extract significantly enhanced amounts of information from return signals as compared to existing systems. The advantages of such high dimensional data come at a cost of increased system and data complexity. For example, since the finer the spectral resolution, the higher the data rate, it becomes impractical to design the sensor to be operated continuously. It is essential to find new ways to preprocess the data which reduce the data rate while at the same time maintaining the information content of the high dimensional signal produced. Four spectral feature design techniques are developed from the Weighted Karhunen-Loeve Transforms: (1) non-overlapping band feature selection algorithm; (2) overlapping band feature selection algorithm; (3) Walsh function approach; and (4) infinite clipped optimal function approach. The infinite clipped optimal function approach is chosen since the features are easiest to find and their classification performance is the best. After the preprocessed data has been received at the ground station, canonical analysis is further used to find the best set of features under the criterion that maximal class separability is achieved. Both 100 dimensional vegetation data and 200 dimensional soil data were used to test the spectral feature design system. It was shown that the infinite clipped versions of the first 16 optimal features had excellent classification performance. The overall probability of correct classification is over 90 percent while providing for a reduced downlink data rate by a factor of 10.

  19. High-speed digital signal normalization for feature identification

    NASA Technical Reports Server (NTRS)

    Ortiz, J. A.; Meredith, B. D.

    1983-01-01

    A design approach for high speed normalization of digital signals was developed. A reciprocal look up table technique is employed, where a digital value is mapped to its reciprocal via a high speed memory. This reciprocal is then multiplied with an input signal to obtain the normalized result. Normalization improves considerably the accuracy of certain feature identification algorithms. By using the concept of pipelining the multispectral sensor data processing rate is limited only by the speed of the multiplier. The breadboard system was found to operate at an execution rate of five million normalizations per second. This design features high precision, a reduced hardware complexity, high flexibility, and expandability which are very important considerations for spaceborne applications. It also accomplishes a high speed normalization rate essential for real time data processing.

  20. The NIMA Kinase Is Required To Execute Stage-Specific Mitotic Functions after Initiation of Mitosis

    PubMed Central

    Govindaraghavan, Meera; Lad, Alisha A.

    2014-01-01

    The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events. PMID:24186954

  1. The Zebra fish cassiopeia Mutant Reveals that SIL Is Required for Mitotic Spindle Organization?

    PubMed Central

    Pfaff, Kathleen L.; Straub, Christian T.; Chiang, Ken; Bear, Daniel M.; Zhou, Yi; Zon, Leonard I.

    2007-01-01

    A critical step in cell division is formation of the mitotic spindle, which is a bipolar array of microtubules that mediates chromosome separation. Here, we report that the SCL-interrupting locus (SIL), a vertebrate-specific cytosolic protein, is necessary for proper mitotic spindle organization in zebrafish and human cells. A homozygous lethal zebrafish mutant, cassiopeia (csp), was identified by a genetic screen for mitotic mutant. csp mutant embryos have an increased mitotic index, have highly disorganized mitotic spindles, and often lack one or both centrosomes. These phenotypes are caused by a loss-of-function mutation in zebrafish sil. To determine if the requirement for SIL in mitotic spindle organization is conserved in mammals, we generated an antibody against human SIL, which revealed that SIL localizes to the poles of the mitotic spindle during metaphase. Furthermore, short hairpin RNA knockdown of SIL in human cells recapitulates the zebrafish csp mitotic spindle defects. These data, taken together, identify SIL as a novel, vertebrate-specific regulator of mitotic spindle assembly. PMID:17576815

  2. The effects of high presentation levels on consonant feature transmission

    NASA Astrophysics Data System (ADS)

    Hornsby, Benjamin W. Y.; Trine, Timothy D.; Ohde, Ralph N.

    2005-09-01

    The effect of high speech presentation levels on consonant recognition and feature transmission was assessed in eight participants with normal hearing. Consonant recognition in noise (0 dB signal-to-noise ratio) was measured at five overall speech levels ranging from 65 to 100 dB SPL. Consistent with the work of others, overall percent correct performance decreased as the presentation level of speech increased [e.g., G. A. Studebaker, R. L. Sherbecoe, D. M. McDaniel, and C. A. Gwaltney, J. Acoust. Soc. Am. 105(4), 2431-2444 (1999)]. Confusion matrices were analyzed in terms of relative percent information transmitted at each speech presentation level, as a function of feature. Six feature sets (voicing, place, nasality, duration, frication, and sonorance) were analyzed. Results showed the feature duration (long consonant duration fricatives) to be most affected by increases in level, while the voicing feature was relatively unaffected by increases in level. In addition, alveolar consonants were substantially affected by level, while palatal consonants were not. While the underlying mechanisms responsible for decreases in performance with level increases are unclear, an analysis of common error patterns at high levels suggests that saturation of the neural response and/or a loss of neural synchrony may play a role.

  3. Loops determine the mechanical properties of mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Heermann, Dieter W.

    2013-03-01

    In mitosis, chromosomes undergo a condensation into highly compacted, rod-like objects. Many models have been put forward for the higher-order organization of mitotic chromosomes including radial loop and hierarchical folding models. Additionally, mechanical properties of mitotic chromosomes under different conditions were measured. However, the internal organization of mitotic chromosomes still remains unclear. Here we present a polymer model for mitotic chromosomes and show how chromatin loops play a major role for their mechanical properties. The key assumption of the model is the ability of the chromatin fibre to dynamically form loops with the help of binding proteins. Our results show that looping leads to a tight compaction and significantly increases the bending rigidity of chromosomes. Moreover, our qualitative prediction of the force elongation behaviour is close to experimental findings. This indicates that the internal structure of mitotic chromosomes is based on self-organization of the chromatin fibre. We also demonstrate how number and size of loops have a strong influence on the mechanical properties. We suggest that changes in the mechanical characteristics of chromosomes can be explained by an altered internal loop structure. YZ gratefully appreciates funding by the German National Academic Foundation (Studienstiftung des deutschen Volkes) and support by the Heidelberg Graduate School for Mathematical and Computational Methods in the Sciences (HGS MathComp).

  4. Feature extraction and classification algorithms for high dimensional data

    NASA Technical Reports Server (NTRS)

    Lee, Chulhee; Landgrebe, David

    1993-01-01

    Feature extraction and classification algorithms for high dimensional data are investigated. Developments with regard to sensors for Earth observation are moving in the direction of providing much higher dimensional multispectral imagery than is now possible. In analyzing such high dimensional data, processing time becomes an important factor. With large increases in dimensionality and the number of classes, processing time will increase significantly. To address this problem, a multistage classification scheme is proposed which reduces the processing time substantially by eliminating unlikely classes from further consideration at each stage. Several truncation criteria are developed and the relationship between thresholds and the error caused by the truncation is investigated. Next an approach to feature extraction for classification is proposed based directly on the decision boundaries. It is shown that all the features needed for classification can be extracted from decision boundaries. A characteristic of the proposed method arises by noting that only a portion of the decision boundary is effective in discriminating between classes, and the concept of the effective decision boundary is introduced. The proposed feature extraction algorithm has several desirable properties: it predicts the minimum number of features necessary to achieve the same classification accuracy as in the original space for a given pattern recognition problem; and it finds the necessary feature vectors. The proposed algorithm does not deteriorate under the circumstances of equal means or equal covariances as some previous algorithms do. In addition, the decision boundary feature extraction algorithm can be used both for parametric and non-parametric classifiers. Finally, some problems encountered in analyzing high dimensional data are studied and possible solutions are proposed. First, the increased importance of the second order statistics in analyzing high dimensional data is recognized. By investigating the characteristics of high dimensional data, the reason why the second order statistics must be taken into account in high dimensional data is suggested. Recognizing the importance of the second order statistics, there is a need to represent the second order statistics. A method to visualize statistics using a color code is proposed. By representing statistics using color coding, one can easily extract and compare the first and the second statistics.

  5. Identifying high-level features of texture perception

    NASA Astrophysics Data System (ADS)

    Rao, A. Ravishankar; Lohse, Gerald L.

    1992-08-01

    A fundamental issue in texture analysis is that of deciding what textural features are important in texture perception, and how they are used. Experiments on human pre-attentive vision have identified several low-level features (such as orientation on blobs, and size of line segments), which are used in texture perception. However, the question of what higher level features of texture are used has not been adequately addressed. We designed an experiment to help identify the relevant higher order features of texture perceived by humans. We used twenty subjects, who were asked to perform an unsupervised classification of thirty pictures from Brodatz's album on texture. Each subject was asked to group these pictures into as many classes as desired. Both hierarchical cluster analysis and non-metric MDS were applied to the pooled similarity matrix generated from the subjects' groupings. A surprising outcome is that the MDS solutions fit the data very well. The stress in the two dimensional case is 0.10, and in the three dimensional case is 0.045. We rendered the original textures in these coordinate systems, and interpreted the (rotated) axes. It appears that the axes in the 2D case correspond to periodicity versus irregularity, and directional versus non-directional. In the 3D case, the third dimension represents the structural complexity of the texture. Furthermore, the clusters identified by the hierarchical cluster analysis remain virtually intact in the MDS solution. The results of our experiment indicate that people use three high level features for texture perception. Future studies are needed to determine the appropriateness of these high-level features for computational texture analysis and classification.

  6. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.

    PubMed

    Giladi, Moshe; Schneiderman, Rosa S; Voloshin, Tali; Porat, Yaara; Munster, Mijal; Blat, Roni; Sherbo, Shay; Bomzon, Zeev; Urman, Noa; Itzhaki, Aviran; Cahal, Shay; Shteingauz, Anna; Chaudhry, Aafia; Kirson, Eilon D; Weinberg, Uri; Palti, Yoram

    2015-01-01

    Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells. PMID:26658786

  7. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells

    PubMed Central

    Giladi, Moshe; Schneiderman, Rosa S; Voloshin, Tali; Porat, Yaara; Munster, Mijal; Blat, Roni; Sherbo, Shay; Bomzon, Zeev; Urman, Noa; Itzhaki, Aviran; Cahal, Shay; Shteingauz, Anna; Chaudhry, Aafia; Kirson, Eilon D; Weinberg, Uri; Palti, Yoram

    2015-01-01

    Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells. PMID:26658786

  8. Stellar absorption features in high-redshift radio galaxies

    SciTech Connect

    Chambers, K.C.; Mccarthy, P.J. Mount Wilson and Las Campanas Observatories, Pasadena, CA )

    1990-05-01

    Evidence for stellar absorption features in a composite ultraviolet spectrum of high-redshift radio galaxies is presented. A large fraction of the ultraviolet light from these objects appears to be starlight. Explanations for the alignment of the optical/infrared continuum and the radio axis in these objects must take this into account. The overall shape of the spectrum suggests that the star formation rate in these objects was higher in the immediate past. 42 refs.

  9. Mitotic trafficking of silicon microparticles

    NASA Astrophysics Data System (ADS)

    Serda, Rita E.; Ferrati, Silvia; Godin, Biana; Tasciotti, Ennio; Liu, Xuewu; Ferrari, Mauro

    2009-11-01

    Multistage carriers were recently introduced by our laboratory, with the concurrent objectives of co-localized delivery of multiple therapeutic agents, the ``theranostic'' integration of bioactive moieties with imaging contrast, and the selective, potentially personalized bypassing of the multiplicity of biological barriers that adversely impact biodistribution of vascularly injected particulates. Mesoporous (``nanoporous'') silicon microparticles were selected as primary carriers in multi-stage devices, with targets including vascular endothelia at pathological lesions. The objective of this study was to evaluate biocompatibility of mesoporous silicon microparticles with endothelial cells using in vitro assays with an emphasis on microparticle compatibility with mitotic events. We observed that vascular endothelial cells, following internalization of silicon microparticles, maintain cellular integrity, as demonstrated by cellular morphology, viability and intact mitotic trafficking of vesicles bearing silicon microparticles. The presence of gold or iron oxide nanoparticles within the porous matrix did not alter the cellular uptake of particles or the viability of endothelial cells subsequent to engulfment of microparticles. Endothelial cells maintained basal levels of IL-6 and IL-8 release in the presence of silicon microparticles. This is the first study that demonstrates polarized, ordered partitioning of endosomes based on tracking microparticles. The finding that mitotic sorting of endosomes is unencumbered by the presence of nanoporous silicon microparticles advocates the use of silicon microparticles for biomedical applications.Multistage carriers were recently introduced by our laboratory, with the concurrent objectives of co-localized delivery of multiple therapeutic agents, the ``theranostic'' integration of bioactive moieties with imaging contrast, and the selective, potentially personalized bypassing of the multiplicity of biological barriers that adversely impact biodistribution of vascularly injected particulates. Mesoporous (``nanoporous'') silicon microparticles were selected as primary carriers in multi-stage devices, with targets including vascular endothelia at pathological lesions. The objective of this study was to evaluate biocompatibility of mesoporous silicon microparticles with endothelial cells using in vitro assays with an emphasis on microparticle compatibility with mitotic events. We observed that vascular endothelial cells, following internalization of silicon microparticles, maintain cellular integrity, as demonstrated by cellular morphology, viability and intact mitotic trafficking of vesicles bearing silicon microparticles. The presence of gold or iron oxide nanoparticles within the porous matrix did not alter the cellular uptake of particles or the viability of endothelial cells subsequent to engulfment of microparticles. Endothelial cells maintained basal levels of IL-6 and IL-8 release in the presence of silicon microparticles. This is the first study that demonstrates polarized, ordered partitioning of endosomes based on tracking microparticles. The finding that mitotic sorting of endosomes is unencumbered by the presence of nanoporous silicon microparticles advocates the use of silicon microparticles for biomedical applications. Electronic supplementary information (ESI) available: Supplementary movies 1 and 2. See DOI: 10.1039/b9nr00138g

  10. Axin localizes to mitotic spindles and centrosomes in mitotic cells

    SciTech Connect

    Kim, Shi-Mun; Choi, Eun-Jin; Song, Ki-Joon; Kim, Sewoon; Seo, Eunjeong; Jho, Eek-Hoon; Kee, Sun-Ho

    2009-04-01

    Wnt signaling plays critical roles in cell proliferation and carcinogenesis. In addition, numerous recent studies have shown that various Wnt signaling components are involved in mitosis and chromosomal instability. However, the role of Axin, a negative regulator of Wnt signaling, in mitosis has remained unclear. Using monoclonal antibodies against Axin, we found that Axin localizes to the centrosome and along mitotic spindles. This localization was suppressed by siRNA specific for Aurora A kinase and by Aurora kinase inhibitor. Interestingly, Axin over-expression altered the subcellular distribution of Plk1 and of phosphorylated glycogen synthase kinase (GSK3{beta}) without producing any notable changes in cellular phenotype. In the presence of Aurora kinase inhibitor, Axin over-expression induced the formation of cleavage furrow-like structures and of prominent astral microtubules lacking midbody formation in a subset of cells. Our results suggest that Axin modulates distribution of Axin-associated proteins such as Plk1 and GSK3{beta} in an expression level-dependent manner and these interactions affect the mitotic process, including cytokinesis under certain conditions, such as in the presence of Aurora kinase inhibitor.

  11. Mitotic force generators and chromosome segregation

    PubMed Central

    Civelekoglu-Scholey, Gul

    2010-01-01

    The mitotic spindle uses dynamic microtubules and mitotic motors to generate the pico-Newton scale forces that are needed to drive the mitotic movements that underlie chromosome capture, alignment and segregation. Here, we consider the biophysical and molecular basis of force-generation for chromosome movements in the spindle, and, with reference to the Drosophila embryo mitotic spindle, we briefly discuss how mathematical modeling can complement experimental analysis to illuminate the mechanisms of chromosome-to-pole motility during anaphase A and spindle elongation during anaphase B. PMID:20221784

  12. Microelasticity of Single Mitotic Chromosomes

    NASA Astrophysics Data System (ADS)

    Poirier, Michael; Eroglu, Sertac; Chatenay, Didier; Marko, John F.; Hirano, Tatsuya

    2000-03-01

    The force-extension behavior of mitotic chromosomes from the newt TVI tumor cell line was studied using micropipette manipulation and force measuring techniques. Reversible, linear elastic response was observed for extensions up to 5 times the native length; the force required to double chromosome length was 1 nanonewton (nN). For further elongations, the linear response teminates at a force plateau of 15 nN and at an extension of 20x. Beyond this extension, the chromosome breaks at elongations between 20x and 70x. These results will be compared to the similar behavior of mitotic chromosomes from explanted newt cells (Poirier, Eroglu, Chatenay and Marko, Mol. Biol. Cell, in press). Also, the effect of biochemical modifications on the elasticity was studied. Ethidium Bromide, which binds to DNA, induces up to a 10 times increase in the Young's modulus. Anti-XCAP-E, which binds to a putative chromosome folding protein, induces up to a 2 times increase in the Young's modulus. Preliminary results on the dynamical relaxation of chromosomes will also be presented. Support of this research through a Biomedical Engineering Research Grant from The Whitaker Foundation is gratefully acknowledged.

  13. Chromatin shapes the mitotic spindle.

    PubMed

    Dinarina, Ana; Pugieux, Cline; Corral, Maria Mora; Loose, Martin; Spatz, Joachim; Karsenti, Eric; Ndlec, Franois

    2009-08-01

    In animal and plant cells, mitotic chromatin locally generates microtubules that self-organize into a mitotic spindle, and its dimensions and bipolar symmetry are essential for accurate chromosome segregation. By immobilizing microscopic chromatin-coated beads on slide surfaces using a microprinting technique, we have examined the effect of chromatin on the dimensions and symmetry of spindles in Xenopus laevis cytoplasmic extracts. While circular spots with diameters around 14-18 microm trigger bipolar spindle formation, larger spots generate an incorrect number of poles. We also examined lines of chromatin with various dimensions. Their length determined the number of poles that formed, with a 6 x 18 microm rectangular patch generating normal spindle morphology. Around longer lines, multiple poles formed and the structures were disorganized. While lines thinner than 10 mum generated symmetric structures, thicker lines induced the formation of asymmetric structures where all microtubules are on the same side of the line. Our results show that chromatin defines spindle shape and orientation. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. PMID:19665972

  14. The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

    PubMed Central

    Carvalhal, Sara; Ribeiro, Susana Abreu; Arocena, Miguel; Kasciukovic, Taciana; Temme, Achim; Koehler, Katrin; Huebner, Angela; Griffis, Eric R.

    2015-01-01

    The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome. PMID:26246606

  15. AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest.

    PubMed

    Domnech, Elena; Maestre, Carolina; Esteban-Martnez, Lorena; Partida, David; Pascual, Rosa; Fernndez-Miranda, Gonzalo; Seco, Esther; Campos-Olivas, Ramn; Prez, Manuel; Megias, Diego; Allen, Katherine; Lpez, Miguel; Saha, Asish K; Velasco, Guillermo; Rial, Eduardo; Mndez, Ral; Boya, Patricia; Salazar-Roa, Mara; Malumbres, Marcos

    2015-10-01

    Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic cells. Prolonged mitotic arrest results in mitophagy-dependent loss of mitochondria, accompanied by reduced ATP levels and the activation of AMPK. Oxidative respiration is replaced by glycolysis owing to AMPK-dependent phosphorylation of PFKFB3 and increased production of this protein as a consequence of mitotic-specific translational activation of its mRNA. Induction of autophagy or inhibition of AMPK or PFKFB3 results in enhanced cell death in mitosis and improves the anti-tumoral efficiency of microtubule poisons in breast cancer cells. Thus, survival of mitotic-arrested cells is limited by their metabolic requirements, a feature with potential implications in cancer therapies aimed to impair mitosis or metabolism in tumour cells. PMID:26322680

  16. High resolution cloud feature tracking on Venus by Galileo

    NASA Technical Reports Server (NTRS)

    Toigo, Anthony; Gierasch, Peter J.; Smith, Michael D.

    1994-01-01

    The Venus cloud deck was monitored in February 1990 for 16 hours at 400 nanometers wavelength by the Galileo imaging system, with a spatial resolution of about 15 km and with image time separations as small as 10 minutes. Velocities are deduced by following the motion of small cloud features. In spite of the high temporal frequence is capable of being detected, no dynamical phenomena are apparent in the velocity data except the already well-known solar tides, possibly altered by the slow 4-day wave and the Hadley circulation. There is no evidence, to a level of approximately 4 m/s, of eddy or wavelike activity. The dominant size of sub-global scale albedo features is 200-500 km, and their contrast is approximately 5%. At low altitudes there are patches of blotchy, cell-like structures but at most locations the markings are streaky. The patterns are similar to those discovered by Mariner 10 and Pioneer Venus (M. J. S. Belton et al., 1976, W. B. Rossow et al., 1980). Scaling arguments are presented to argue that the mesoscale blotchy cell-like cloud patterns are caused by local dynamics driven in a shallow layer by differential absorption of sunlight. It is also argued that mesoscale albedo features are either streaky or cell-like simply depending on whether the horizontal shear of the large scale flow exceeds a certain critical value.

  17. High Spatial Velocity Features in the Orion Nebula,

    NASA Astrophysics Data System (ADS)

    O'Dell, C. R.; Henney, W. J.

    2008-10-01

    We have used widely spaced in time Hubble Space Telescope images to determine tangential velocities of features associated with outflows from young stars. These observations were supplemented by ground-based telescope spectroscopy, and from the resultant radial velocities, space velocities were determined for many outflows. Numerous new moving features were found and grouped into known and newly assigned Herbig-Haro objects. It was found that stellar outflow is highly discontinuous, as frequently is the case, with long-term gaps of a few hundred years, and that these outflow periods are marked by staccato bursts over periods of about ten years. Although this has been observed in other regions, the Orion Nebula Cluster presents the richest display of this property. Most of the large-scale Herbig-Haro objects in the brightest part of the Orion Nebula appear to originate from a small region northeast of the strong Orion-S radio and infrared sources. With the possible exception of HH 203, we are not able to identify specific stellar sources, but do identify candidate sources for several other bright Herbig-Haro objects. We find that there are optical features in the BN-KL region that can be related to the known large-scale outflow that originates there. We find additional evidence for this outflow originating 500-1000 years ago. Based on observations at the San Pedro Martir Observatory operated by the Universidad Nacional Autónoma de México.

  18. [Metabolism features of bacteria resistant to high concentrations of chromate].

    PubMed

    Smirnova, G F; Podgorski?, V S

    2013-01-01

    Twenty strains of bacteria resistant to high concentrations of chromate were isolated from different ecological niches. They were able to reduce chromate to compounds of trivalent chromium--nonsoluble chromium hydroxide or soluble crystalline hydrates of trivalent chromium. The growth features of these microorganisms on media containing chromate at high concentrations (up to 20.0 g/l) are described. Besides chromate bacteria can reduce vanadate to compounds of V(4+) and Mo(6+) to Mo(5+). The best reduction takes place on the media where MPB. glucose or ethanol serves as the source of carbon. The growth and reduction of anion-in-study did not occur on organic acids. It was shown that tungstate, chlorate or perchlorate were not toxic for the studied bacteria up to concentrations of 10.0 g/l, however were not reduced by these microorganisms. The most active strains belong to genera Pseudomonas, Oerskovia, Bacillus, Micrococcus. PMID:23720958

  19. Mitotic and mitogenic Wnt signalling

    PubMed Central

    Niehrs, Christof; Acebron, Sergio P

    2012-01-01

    Canonical Wnt signalling plays an important role in development, tissue homeostasis, and cancer. At the cellular level, canonical Wnt signalling acts by regulating cell fate, cell growth, and cell proliferation. With regard to proliferation, there is increasing evidence for a complex interaction between canonical Wnt signalling and the cell cycle. Mitogenic Wnt signalling regulates cell proliferation by promoting G1 phase. In mitosis, components of the Wnt signalling cascade function directly in spindle formation. Moreover, Wnt signalling is strongly activated in mitosis, suggesting that ‘mitotic Wnt signalling' plays an important role to orchestrate a cell division program. Here, we review the complex interplay between Wnt signalling and the cell cycle. PMID:22617425

  20. Practical multi-featured perfect absorber utilizing high conductivity silicon

    NASA Astrophysics Data System (ADS)

    Gok, Abdullah; Yilmaz, Mehmet; Bıyıklı, Necmi; Topallı, Kağan; Okyay, Ali K.

    2016-03-01

    We designed all-silicon, multi-featured band-selective perfect absorbing surfaces based on CMOS compatible processes. The center wavelength of the band-selective absorber can be varied between 2 and 22 μm while a bandwidth as high as 2.5 μm is demonstrated. We used a silicon-on-insulator (SOI) wafer which consists of n-type silicon (Si) device layer, silicon dioxide (SiO2) as buried oxide layer, and n-type Si handle layer. The center wavelength and bandwidth can be tuned by adjusting the conductivity of the Si device and handle layers as well as the thicknesses of the device and buried oxide layers. We demonstrate proof-of-concept absorber surfaces experimentally. Such absorber surfaces are easy to microfabricate because the absorbers do not require elaborate microfabrication steps such as patterning. Due to the structural simplicity, low-cost fabrication, wide spectrum range of operation, and band properties of the perfect absorber, the proposed multi-featured perfect absorber surfaces are promising for many applications. These include sensing devices, surface enhanced infrared absorption applications, solar cells, meta-materials, frequency selective sensors and modulators.

  1. High-Throughput Quantification of Phenotype Heterogeneity Using Statistical Features

    PubMed Central

    Chaddad, Ahmad; Tanougast, Camel

    2015-01-01

    Statistical features are widely used in radiology for tumor heterogeneity assessment using magnetic resonance (MR) imaging technique. In this paper, feature selection based on decision tree is examined to determine the relevant subset of glioblastoma (GBM) phenotypes in the statistical domain. To discriminate between active tumor (vAT) and edema/invasion (vE) phenotype, we selected the significant features using analysis of variance (ANOVA) with p value < 0.01. Then, we implemented the decision tree to define the optimal subset features of phenotype classifier. Nave Bayes (NB), support vector machine (SVM), and decision tree (DT) classifier were considered to evaluate the performance of the feature based scheme in terms of its capability to discriminate vAT from vE. Whole nine features were statistically significant to classify the vAT from vE with p value < 0.01. Feature selection based on decision tree showed the best performance by the comparative study using full feature set. The feature selected showed that the two features Kurtosis and Skewness achieved a highest range value of 58.3375.00% accuracy classifier and 73.8892.50% AUC. This study demonstrated the ability of statistical features to provide a quantitative, individualized measurement of glioblastoma patient and assess the phenotype progression. PMID:26640485

  2. Radar-anomalous, high-altitude features on Venus

    NASA Technical Reports Server (NTRS)

    Muhleman, Duane O.; Butler, Bryan J.

    1992-01-01

    Over nearly all of the surface of Venus the reflectivity and emissivity at centimeter wavelengths are about 0.15 and 0.85 respectively. These values are consistent with moderately dense soils and rock populations, but the mean reflectivity is about a factor of 2 greater than that for the Moon and other terrestrial planets. Pettingill and Ford, using Pioneer Venus reflectivities and emissivities, found a number of anomalous features on Venus that showed much higher reflectivities and much lower emissivities with both values approaching 0.5. These include Maxwell Montes, a number of high regions in Aphrodite Terra and Beta Regio, and several isolated mountain peaks. Most of the features are at altitudes above the mean radius by 2 to 3 km or more. However, such features have been found in the Magellan data at low altitudes and the anomalies do not exist on all high structures, Maat Mons being the most outstanding example. A number of papers have been written that attempt to explain the phenomena in terms of the geochemistry balance of weathering effects on likely surface minerals. The geochemists have shown that the fundamentally basaltic surface would be stable at the temperatures and pressures of the mean radius in the form of magnetite, but would evolve to pyrite and/or pyrrhotite in the presence of sulfur-bearing compounds such as SO2. Pyrite will be stable at altitudes above 4 or 5 km on Venus. Although the geochemical arguments are rather compelling, it is vitally important to rationally look at other explanations for radar and radio emission measurements such as that presented by Tryka and Muhleman. The radar reflectivity values are retrieved from the raw Magellan backscatter measurements by fitting the Hagfors' radar scattering model in which a surface roughness parameters and a normal incidence electrical reflectivity are estimated. The assumptions of the theory behind the model must be considered carefully before the results can be believed. These include that the surface roughness exists only at horizontal scales large compared to the wavelength, the vertical deviations are gaussianly distributed, there is no shadowing, and that the reflection occurs at the interface of two homogeneous dielectric half-spaces. Probably all these conditions are violated at the anomalous features under discussion. The most important of these is the homogeneity of the near surface of Venus, particularly in highlands. Under the assumptions of the theory, all of the radio energy is reflected by the impedance jump at the very boundary. However, in heterogeneous soil some fraction of the illuminating energy is propagated into the soil and then scattered back out by impedance discontinuities such as rock, voids, and cracks. In light soils, the latter effect can overwhelm the scattering effects of the true surface and greatly enhance the backscatter power, suggesting a much higher value of an effective dielectric constant that would be estimated from Hagfors' model.

  3. Orthologues of the Anaphase-Promoting Complex/Cyclosome Coactivators Cdc20p and Cdh1p Are Important for Mitotic Progression and Morphogenesis in Candida albicans ?

    PubMed Central

    Chou, Hsini; Glory, Amandeep; Bachewich, Catherine

    2011-01-01

    The conserved anaphase-promoting complex/cyclosome (APC/C) system mediates protein degradation during mitotic progression. Conserved coactivators Cdc20p and Cdh1p regulate the APC/C during early to late mitosis and G1 phase. Candida albicans is an important fungal pathogen of humans, and it forms highly polarized cells when mitosis is blocked through depletion of the polo-like kinase Cdc5p or other treatments. However, the mechanisms governing mitotic progression and associated polarized growth in the pathogen are poorly understood. In order to gain insights into these processes, we characterized C. albicans orthologues of Cdc20p and Cdh1p. Cdc20p-depleted cells were blocked in early or late mitosis with elevated levels of Cdc5p and the mitotic cyclin Clb2p, suggesting that Cdc20p is essential and has some conserved functions during mitosis. However, the yeast cells formed highly polarized buds in contrast to the large doublets of S. cerevisiae cdc20 mutants, implying a distinct role in morphogenesis. In comparison, cdh1?/cdh1? cells were viable but showed enrichment of Clb2p and Cdc5p, suggesting that Cdh1p may influence mitotic exit. The cdh1?/cdh1? phenotype was pleiotropic, consisting of normal or enlarged yeast, pseudohyphae, and some elongated buds, whereas S. cerevisiae cdh1? yeast cells were reduced in size. Thus, C. albicans Cdh1p may have some distinct functions. Finally, absence of Cdh1p or Cdc20p had a minor or no effect on hyphal development, respectively. Overall, the results suggest that Cdc20p and Cdh1p may be APC/C activators that are important for mitosis but also morphogenesis in C. albicans. Their novel features imply additional variations in function and underscore rewiring in the emerging mitotic regulatory networks of the pathogen. PMID:21398510

  4. The chromosomal passenger complex (CPC) as a key orchestrator of orderly mitotic exit and cytokinesis

    PubMed Central

    Kitagawa, Mayumi; Lee, Sang Hyun

    2015-01-01

    Understanding the molecular network of orderly mitotic exit to re-establish a functional interphase nucleus is critical because disordered mitotic exit inevitably leads to genomic instability. In contrast to the mechanisms of the entrance to mitosis, however, little is known about what controls the orderly exit from mitosis, particularly in mammalian cells. The chromosomal passenger complex (CPC), which is composed of Aurora B, INCENP, Borealin and Survivin, is one of the most widely studied and highly conserved hetero-tetrameric complexes. The CPC orchestrates proper chromosome segregation with cytokinesis by targeting to specific locations at different stages of mitosis. Recent studies reveal that controlling CPC localization and Aurora B kinase activity also serves as a key surveillance mechanism for the orderly mitotic exit. This ensures the reformation of a functional interphase nucleus from condensed mitotic chromosomes by delaying mitotic exit and cytokinetic processes in response to defects in chromosome segregation. In this review, we will summarize the latest insight into the molecular mechanisms that regulate CPC localization during mitotic exit and discuss how targeting Aurora B activity to different locations at different times impacts executing multiple mitotic exit events in order and recently proposed surveillance mechanisms. Finally, we briefly discuss the potential implication of deregulated Aurora B in inducing genomic damage and tumorigenesis with current efforts in targeting Aurora B activity for anti-cancer therapy. PMID:25798441

  5. On the molecular mechanisms of mitotic kinase activation.

    PubMed

    Bayliss, Richard; Fry, Andrew; Haq, Tamanna; Yeoh, Sharon

    2012-11-01

    During mitosis, human cells exhibit a peak of protein phosphorylation that alters the behaviour of a significant proportion of proteins, driving a dramatic transformation in the cell's shape, intracellular structures and biochemistry. These mitotic phosphorylation events are catalysed by several families of protein kinases, including Auroras, Cdks, Plks, Neks, Bubs, Haspin and Mps1/TTK. The catalytic activities of these kinases are activated by phosphorylation and through protein-protein interactions. In this review, we summarize the current state of knowledge of the structural basis of mitotic kinase activation mechanisms. This review aims to provide a clear and comprehensive primer on these mechanisms to a broad community of researchers, bringing together the common themes, and highlighting specific differences. Along the way, we have uncovered some features of these proteins that have previously gone unreported, and identified unexplored questions for future work. The dysregulation of mitotic kinases is associated with proliferative disorders such as cancer, and structural biology will continue to play a critical role in the development of chemical probes used to interrogate disease biology and applied to the treatment of patients. PMID:23226601

  6. On the molecular mechanisms of mitotic kinase activation

    PubMed Central

    Bayliss, Richard; Fry, Andrew; Haq, Tamanna; Yeoh, Sharon

    2012-01-01

    During mitosis, human cells exhibit a peak of protein phosphorylation that alters the behaviour of a significant proportion of proteins, driving a dramatic transformation in the cell's shape, intracellular structures and biochemistry. These mitotic phosphorylation events are catalysed by several families of protein kinases, including Auroras, Cdks, Plks, Neks, Bubs, Haspin and Mps1/TTK. The catalytic activities of these kinases are activated by phosphorylation and through proteinprotein interactions. In this review, we summarize the current state of knowledge of the structural basis of mitotic kinase activation mechanisms. This review aims to provide a clear and comprehensive primer on these mechanisms to a broad community of researchers, bringing together the common themes, and highlighting specific differences. Along the way, we have uncovered some features of these proteins that have previously gone unreported, and identified unexplored questions for future work. The dysregulation of mitotic kinases is associated with proliferative disorders such as cancer, and structural biology will continue to play a critical role in the development of chemical probes used to interrogate disease biology and applied to the treatment of patients. PMID:23226601

  7. A comprehensive model to predict mitotic division in budding yeasts

    PubMed Central

    Sutradhar, Sabyasachi; Yadav, Vikas; Sridhar, Shreyas; Sreekumar, Lakshmi; Bhattacharyya, Dibyendu; Ghosh, Santanu Kumar; Paul, Raja; Sanyal, Kaustuv

    2015-01-01

    High-fidelity chromosome segregation during cell division depends on a series of concerted interdependent interactions. Using a systems biology approach, we built a robust minimal computational model to comprehend mitotic events in dividing budding yeasts of two major phyla: Ascomycota and Basidiomycota. This model accurately reproduces experimental observations related to spindle alignment, nuclear migration, and microtubule (MT) dynamics during cell division in these yeasts. The model converges to the conclusion that biased nucleation of cytoplasmic microtubules (cMTs) is essential for directional nuclear migration. Two distinct pathways, based on the population of cMTs and cortical dyneins, differentiate nuclear migration and spindle orientation in these two phyla. In addition, the model accurately predicts the contribution of specific classes of MTs in chromosome segregation. Thus we present a model that offers a wider applicability to simulate the effects of perturbation of an event on the concerted process of the mitotic cell division. PMID:26310442

  8. A comprehensive model to predict mitotic division in budding yeasts.

    PubMed

    Sutradhar, Sabyasachi; Yadav, Vikas; Sridhar, Shreyas; Sreekumar, Lakshmi; Bhattacharyya, Dibyendu; Ghosh, Santanu Kumar; Paul, Raja; Sanyal, Kaustuv

    2015-11-01

    High-fidelity chromosome segregation during cell division depends on a series of concerted interdependent interactions. Using a systems biology approach, we built a robust minimal computational model to comprehend mitotic events in dividing budding yeasts of two major phyla: Ascomycota and Basidiomycota. This model accurately reproduces experimental observations related to spindle alignment, nuclear migration, and microtubule (MT) dynamics during cell division in these yeasts. The model converges to the conclusion that biased nucleation of cytoplasmic microtubules (cMTs) is essential for directional nuclear migration. Two distinct pathways, based on the population of cMTs and cortical dyneins, differentiate nuclear migration and spindle orientation in these two phyla. In addition, the model accurately predicts the contribution of specific classes of MTs in chromosome segregation. Thus we present a model that offers a wider applicability to simulate the effects of perturbation of an event on the concerted process of the mitotic cell division. PMID:26310442

  9. Mitotic regulation by NIMA-related kinases

    PubMed Central

    O'Regan, Laura; Blot, Joelle; Fry, Andrew M

    2007-01-01

    The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non-dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets. PMID:17727698

  10. High Resolution Urban Feature Extraction for Global Population Mapping using High Performance Computing

    SciTech Connect

    Vijayaraj, Veeraraghavan; Bright, Eddie A; Bhaduri, Budhendra L

    2007-01-01

    The advent of high spatial resolution satellite imagery like Quick Bird (0.6 meter) and IKONOS (1 meter) has provided a new data source for high resolution urban land cover mapping. Extracting accurate urban regions from high resolution images has many applications and is essential to the population mapping efforts of Oak Ridge National Laboratory's (ORNL) LandScan population distribution program. This paper discusses an automated parallel algorithm that has been implemented on a high performance computing environment to extract urban regions from high resolution images using texture and spectral features

  11. Micromechanical study of mitotic chromosome structure

    NASA Astrophysics Data System (ADS)

    Marko, John

    2011-03-01

    Our group has developed micromanipulation techniques for study of the highly compacted mitotic form of chromosome found in eukaryote cells during cell division. Each metaphase chromosome contains two duplicate centimeter-long DNA molecules, folded up by proteins into cylindrical structures several microns in length. Native chromosomes display linear and reversible stretching behavior over a wide range of extensions (up to 5x native length for amphibian chromosomes), described by a Young modulus of about 300 Pa. Studies using DNA-cutting and protein-cutting enzymes have revealed that metaphase chromosomes behave as a network of chromatin fibers held together by protein-based isolated crosslinks. Our results are not consistent with the more classical model of loops of chromatin attached to a protein-based structural organizer or ``scaffold". In short, our experiments indicate that metaphase chromosomes can be considered to be ``gels" of chromatin; the stretching modulus of a whole chromosome is consistent with stretching of the chromatin fibers contained within it. Experiments using topoisomerases suggest that topological constraints may play an appreciable role in confining chromatin in the metaphase chromosome. Finally, recent experiments on human chromosomes will be reviewed, including results of experiments where chromosome-folding proteins are specifically depleted using siRNA methods. Supported by NSF-MCB-1022117, DMR-0715099, PHY-0852130, DMR-0520513, NCI 1U54CA143869-01 (NU-PS-OC), and the American Heart Association.

  12. p53 mutation and mitotic infidelity.

    PubMed

    Tarapore, P; Fukasawa, K

    2000-01-01

    Chromosome instability (a high frequency of chromosomal loss and gain and genome doubling, often referred to as karyotypic instability) is one of the major characteristics of cancer cells. It facilitates carcinogenesis by increasing the chance of specific mutations responsible for malignant phenotypes. Chromosome instability in most cases reflects the occurrence of defective mitosis, including unequal distribution of chromosomes to daughter cells and failure to undergo cytokinesis, which leads to generation of aneuploid cells. Both in vivo and in vitro, chromosome instability has been shown to correlate with loss or mutation of the p53 tumor suppressor protein, the product of one of the most frequently mutated genes in cancer. The major function of p53 is to prevent cells from proceeding through the cell cycle when cells experience stress, insults, or errors that disturb the preprogrammed cell cycle progression. During the last several years, significant advances have been made in understanding how p53 is involved in the regulation of mitosis and how loss or mutation of p53 affects mitotic fidelity, which will be the subject of this review. PMID:10705877

  13. Toward a systems-level view of mitotic checkpoints.

    PubMed

    Ibrahim, Bashar

    2015-03-01

    Reproduction and natural selection are the key elements of life. In order to reproduce, the genetic material must be doubled, separated and placed into two new daughter cells, each containing a complete set of chromosomes and organelles. In mitosis, transition from one process to the next is guided by intricate surveillance mechanisms, known as the mitotic checkpoints. Dis-regulation of cell division through checkpoint malfunction can lead to developmental defects and contribute to the development or progression of tumors. This review approaches two important mitotic checkpoints, the spindle assembly checkpoint (SAC) and the spindle position checkpoint (SPOC). The highly conserved spindle assembly checkpoint (SAC) controls the onset of anaphase by preventing premature segregation of the sister chromatids of the duplicated genome, to the spindle poles. In contrast, the spindle position checkpoint (SPOC), in the budding yeast Saccharomyces cerevisiae, ensures that during asymmetric cell division mitotic exit does not occur until the spindle is properly aligned with the cell polarity axis. Although there are no known homologs, there is indication that functionally similar checkpoints exist also in animal cells. This review can be regarded as an "executable model", which could be easily translated into various quantitative concrete models like Petri nets, ODEs, PDEs, or stochastic particle simulations. It can also function as a base for developing quantitative models explaining the interplay of the various components and proteins controlling mitosis. PMID:25722206

  14. The Drosophila microtubule-associated protein mars stabilizes mitotic spindles by crosslinking microtubules through its N-terminal region.

    PubMed

    Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

    2013-01-01

    Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs. PMID:23593258

  15. Fluorescent in situ hybridization on mitotic chromosomes of mosquitoes.

    PubMed

    Timoshevskiy, Vladimir A; Sharma, Atashi; Sharakhov, Igor V; Sharakhova, Maria V

    2012-01-01

    Fluorescent in situ hybridization (FISH) is a technique routinely used by many laboratories to determine the chromosomal position of DNA and RNA probes. One important application of this method is the development of high-quality physical maps useful for improving the genome assemblies for various organisms. The natural banding pattern of polytene and mitotic chromosomes provides guidance for the precise ordering and orientation of the genomic supercontigs. Among the three mosquito genera, namely Anopheles, Aedes, and Culex, a well-established chromosome-based mapping technique has been developed only for Anopheles, whose members possess readable polytene chromosomes. As a result of genome mapping efforts, 88% of the An. gambiae genome has been placed to precise chromosome positions. Two other mosquito genera, Aedes and Culex, have poorly polytenized chromosomes because of significant overrepresentation of transposable elements in their genomes. Only 31 and 9% of the genomic supercontings have been assigned without order or orientation to chromosomes of Ae. aegypti and Cx. quinquefasciatus, respectively. Mitotic chromosome preparation for these two species had previously been limited to brain ganglia and cell lines. However, chromosome slides prepared from the brain ganglia of mosquitoes usually contain low numbers of metaphase plates. Also, although a FISH technique has been developed for mitotic chromosomes from a cell line of Ae. aegypti, the accumulation of multiple chromosomal rearrangements in cell line chromosomes makes them useless for genome mapping. Here we describe a simple, robust technique for obtaining high-quality mitotic chromosome preparations from imaginal discs (IDs) of 4th instar larvae which can be used for all three genera of mosquitoes. A standard FISH protocol is optimized for using BAC clones of genomic DNA as a probe on mitotic chromosomes of Ae. aegypti and Cx. quinquefasciatus, and for utilizing an intergenic spacer (IGS) region of ribosomal DNA (rDNA) as a probe on An. gambiae chromosomes. In addition to physical mapping, the developed technique can be applied to population cytogenetics and chromosome taxonomy/systematics of mosquitoes and other insect groups. PMID:23007640

  16. Copy Number Suppressors of the Aspergillus nidulans nimA1 Mitotic Kinase Display Distinctive and Highly Dynamic Cell Cycle-Regulated Locations?

    PubMed Central

    Ukil, Leena; Varadaraj, Archana; Govindaraghavan, Meera; Liu, Hui-Lin; Osmani, Stephen A.

    2008-01-01

    The Aspergillus nidulans NIMA kinase is essential for mitosis and is the founding member of the conserved NIMA-related kinase (Nek) family of protein kinases. To gain insight into NIMA function, a copy number suppression screen has been completed that defines three proteins termed MCNA, MCNB, and MCNC (multi-copy-number suppressor of nimA1 A, B, and C). All display a distinctive and dynamic cell cycle-specific distribution. MCNC has weak similarity to Saccharomyces cerevisiae Def1 within a shared CUE-like domain. MCNC, like Def1, is a cytoplasmic protein with slow mobility during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its deletion causes polarization defects and a small colony phenotype. MCNC enters nuclei during mitosis. In contrast, MCNB is a nuclear protein displaying increased nuclear levels as cells progress through interphase but is lost from nuclei at mitosis. MCNB is highly related to the Schizosaccharomyces pombe forkhead transcription factor Sep1 and is likely a transcriptional activator of nimA. Most surprisingly, MCNA, a protein restricted to the aspergilli and pathogenic systemic dimorphic fungi (the Eurotiomycetes), defines a nuclear body located near nucleoli at the nuclear periphery of G2 nuclei. During progression through mitosis, the MCNA body is excluded from nuclei. Cytoplasmic MCNA bodies then diminish during early stages of interphase, and single MCNA bodies are formed within nuclei as interphase progresses. Three sites of MCNA phosphorylation were mapped and mutated to implicate proline-directed phosphorylation in the equal segregation of MCNA during the cell cycle. The data indicate all three MCN proteins likely have cell cycle functions. PMID:18931041

  17. Increased mitotic activity as a negative prognostic indicator in pleomorphic xanthoastrocytoma. Case report.

    PubMed

    Macaulay, R J; Jay, V; Hoffman, H J; Becker, L E

    1993-11-01

    Pleomorphic xanthoastrocytoma is a recently characterized neoplasm with a favorable prognosis despite aggressive histological features. The authors report a case of pleomorphic xanthoastrocytoma that recurred 4 years after complete gross resection. The original tumor exhibited histological features characteristic of this neoplasm, but up to 4 mitoses/10 high-power fields were present focally. The recurrent tumor contained small foci of classical pleomorphic xanthoastrocytoma, but consisted predominantly of glioblastoma multiforme. Transitional zones contained nests of glial fibrillary acidic protein (GFAP)-immunopositive cells surrounded by delicate collagenous and reticulin-rich septa. Electron microscopy of the transitional zone showed continuous basal lamina investing cells containing bundles of intermediate filaments. These were GFAP-positive by immunogold electron microscopy, confirming the astrocytic nature of pleomorphic xanthoastrocytoma. This example illustrates the capacity of this tumor to evolve into glioblastoma. The indolent clinical behavior of most pleomorphic xanthoastrocytomas is evident from a literature review, which confirms the prolonged survival of many patients after onset of symptoms. Completeness of excision, subjectively assessed at surgery, did not influence the risk of recurrence or survival up to 10 years after initial resection. Postoperative radiotherapy did not improve survival, but may reduce the probability of recurrence; more studies are needed to corroborate this finding. The data compiled herein support the designation of pleomorphic xanthoastrocytoma as a distinct astrocytic neoplasm with a favorable prognosis. An increased mitotic rate has not previously been correlated with a worse outcome, and should not be used to exclude this diagnosis. However, anaplastic transformation of pleomorphic xanthoastrocytoma confers a much worse prognosis, and this case suggests that increased mitotic activity may be a negative prognostic indicator since it may herald subsequent anaplastic transformation. PMID:8410257

  18. Design features and performance of a high speed TDMA demodulator

    NASA Astrophysics Data System (ADS)

    Wallace, R. L.

    Design features and performance ranges of a new TDMA demodulator are presented. The device includes 500 MHz bandwidth amplifier stages with 15 dB gain, a bandpass filter for band rejection and receiver noise filtering, a pin attenuator, and a diode limiter to minimize the driving force variations and prevent saturation and overload effects. The demodulator is capable of burst-to-burst I.F. leveling, optimal coherent carrier recovery, and symbol clock recovery in 1.5 microsec. Less than 1 dB modem loss in data demodulation is achieved, compared with theoretical values, using Nyquist, matched filtering techniques at the baseband. Finally, the device has a time sampled, digitized COSTAS recovered carrier phasing loop and operates at a data rate of 48 Mbps.

  19. Rapid measurement of mitotic spindle orientation in cultured mammalian cells.

    PubMed

    Decarreau, Justin; Driver, Jonathan; Asbury, Charles; Wordeman, Linda

    2014-01-01

    Factors that influence the orientation of the mitotic spindle are important for the maintenance of stem cell populations and in cancer development. However, screening for these factors requires rapid quantification of alterations of the angle of the mitotic spindle in cultured cell lines. Here we describe a method to image mitotic cells and rapidly score the angle of the mitotic spindle using a simple MATLAB application to analyze a stack of Z-images. PMID:24633791

  20. Rapid measurement of mitotic spindle orientation in cultured mammalian cells

    PubMed Central

    Decarreau, Justin; Driver, Jonathan; Asbury, Charles; Wordeman, Linda

    2014-01-01

    Summary Factors that influence the orientation of the mitotic spindle are important for the maintenance of stem cell populations and in cancer development. However, screening for these factors requires rapid quantification of alterations of the angle of the mitotic spindle in cultured cell lines. Here we describe a method to image mitotic cells and rapidly score the angle of the mitotic spindle using a simple MATLAB application to analyze a stack of Z-images. PMID:24633791

  1. Mitotic Stress and Chromosomal Instability in Cancer

    PubMed Central

    Malumbres, Marcos

    2012-01-01

    Cell cycle deregulation is a common motif in human cancer, and multiple therapeutic strategies are aimed to prevent tumor cell proliferation. Whereas most current therapies are designed to arrest cell cycle progression either in G1/S or in mitosis, new proposals include targeting the intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) or aneuploidy (a genomic composition that differs from diploid) that many tumor cells display. Why tumors cells are chromosomally unstable or aneuploid and what are the consequences of these alterations are not completely clear at present. Several mitotic regulators are overexpressed as a consequence of oncogenic alterations, and they are likely to alter the proper regulation of chromosome segregation in cancer cells. In this review, we propose the relevance of TPX2, a mitotic regulator involved in the formation of the mitotic spindle, in oncogene-induced mitotic stress. This protein, as well as its partner Aurora-A, is frequently overexpressed in human cancer, and its deregulation may participate not only in chromosome numeric aberrations but also in other forms of genomic instability in cancer cells. PMID:23634259

  2. Concentrating on the mitotic spindle.

    PubMed

    Maddox, Paul S; Ladouceur, Anne-Marie

    2015-08-31

    In eukaryotes, the microtubule-based spindle drives chromosome segregation. In this issue, Schweizer et al. (2015; J. Cell Biol. http://dx.doi.org/10.1083/jcb.201506107) find that the spindle area is demarcated by a semipermeable organelle barrier. Molecular crowding, which is microtubule independent, causes the enrichment and/or retention of crucial factors in the spindle region. Their results add an important new feature to the models of how this structure assembles and is regulated. PMID:26323687

  3. Identification of Drosophila Mitotic Genes by Combining Co-Expression Analysis and RNA Interference

    PubMed Central

    Somma, Maria Patrizia; Ceprani, Francesca; Bucciarelli, Elisabetta; Naim, Valeria; De Arcangelis, Valeria; Piergentili, Roberto; Palena, Antonella; Ciapponi, Laura; Giansanti, Maria Grazia; Pellacani, Claudia; Petrucci, Romano; Cenci, Giovanni; Vern, Fiammetta; Fasulo, Barbara; Goldberg, Michael L.; Di Cunto, Ferdinando; Gatti, Maurizio

    2008-01-01

    RNAi screens have, to date, identified many genes required for mitotic divisions of Drosophila tissue culture cells. However, the inventory of such genes remains incomplete. We have combined the powers of bioinformatics and RNAi technology to detect novel mitotic genes. We found that Drosophila genes involved in mitosis tend to be transcriptionally co-expressed. We thus constructed a co-expressionbased list of 1,000 genes that are highly enriched in mitotic functions, and we performed RNAi for each of these genes. By limiting the number of genes to be examined, we were able to perform a very detailed phenotypic analysis of RNAi cells. We examined dsRNA-treated cells for possible abnormalities in both chromosome structure and spindle organization. This analysis allowed the identification of 142 mitotic genes, which were subdivided into 18 phenoclusters. Seventy of these genes have not previously been associated with mitotic defects; 30 of them are required for spindle assembly and/or chromosome segregation, and 40 are required to prevent spontaneous chromosome breakage. We note that the latter type of genes has never been detected in previous RNAi screens in any system. Finally, we found that RNAi against genes encoding kinetochore components or highly conserved splicing factors results in identical defects in chromosome segregation, highlighting an unanticipated role of splicing factors in centromere function. These findings indicate that our co-expressionbased method for the detection of mitotic functions works remarkably well. We can foresee that elaboration of co-expression lists using genes in the same phenocluster will provide many candidate genes for small-scale RNAi screens aimed at completing the inventory of mitotic proteins. PMID:18797514

  4. Emission features in the spectrum of NGC 7027 near 3. 3 microns at very high resolution

    SciTech Connect

    Lowe, R.P.; Moorhead, J.M.; Wehlau, W.H.; Maillard, J.P. CNRS, Institut d'Astrophysique, Paris )

    1991-02-01

    A very high resolution spectrum is presented of the planetary nebula NGC 7027 over a 200/cm interval centered at 2950/cm, and the features found are described: (1) nebular continuum, (2) atomic recombination lines of H and He II, and (3) three broader emission features of uncertain origin. For the latter the first evidence is presented that the 3.46 micron feature and possibly the 3.40 micron feature are resolvable into a sequence of narrower features. The interpretation of the broader features is discussed in terms of the hypothesis of identification with emission by polycyclic aromatic hydrocarbons. 18 refs.

  5. Practical features of illumination with high pressure sodium lamps

    SciTech Connect

    Corth, R.

    1983-06-01

    A number of concerns raised about the health effects of high pressure sodium lamps (HPS) are discussed. The notion of a ''natural'' human photic environment based on sunlight is disputed. Humans are better adapted to the ''greenish'' spectral composition of forest light than to direct sunlight. It is ironic that the artificial light source which has received the most disapproval, cool white flourescent lamp, has a spectral composition similar to that of forest light. HPS is also available in a full range of colors. Some successful examples of HPS--from North Division High School, in Milwaukee, Wisconsin, to museum exhibits at National Geographic in Washington--are listed.

  6. STEM High School Communities: Common and Differing Features

    ERIC Educational Resources Information Center

    Tofel-Grehl, Colby; Callahan, Carolyn M.

    2014-01-01

    Using observations and interviews, the researchers explore the experiences and perspectives of students, teachers, and administrators at six specialized high schools with a focus on science, technology, engineering, and mathematics (STEM) as they pertain to the practices and structures affecting student outcomes. Four themes were found to be…

  7. STEM High School Communities: Common and Differing Features

    ERIC Educational Resources Information Center

    Tofel-Grehl, Colby; Callahan, Carolyn M.

    2014-01-01

    Using observations and interviews, the researchers explore the experiences and perspectives of students, teachers, and administrators at six specialized high schools with a focus on science, technology, engineering, and mathematics (STEM) as they pertain to the practices and structures affecting student outcomes. Four themes were found to be

  8. Features of structure formation in high-viscosity paraffinic crudes

    SciTech Connect

    Ratov, A.N.; Ashmyan, K.D.; Nemirovskaya, G.B.

    1995-09-01

    In the design of petroleum refining processes for high-viscosity crudes and in solving problems associated with transportation of the crudes and increasing the recovery of oil from the formation, the viscosity characteristics and other rheological properties of the oil are of prime importance. These properties are governed to a considerable degree by associative interactions of the components of the crude. Here we are presenting results from an investigation of the viscosity properties of a number of crudes from fields in Ul`yanov Oblast, located in the Severo-Vostochnaya (Northeastern) and Filippovka groups of fields, and also its Yuzhnyi (Southern) pocket. These crudes differ among themselves in content of resins and asphaltenes and contain rather large amounts of high-molecular weight paraffin waxes; also, these crudes have high densities (up to 900 kg/cubic meter) and high viscosities (up to 600 mPa-sec). For this particular set of crudes, we have found certain correlations between rheological properties and composition.

  9. Polyoma small T antigen triggers cell death via mitotic catastrophe

    PubMed Central

    Fernando, Arun T Pores; Andrabi, Shaida; Cizmecioglu, Onur; Zhu, Cailei; Livingston, David M.; Higgins, Jonathan M.G; Schaffhausen, Brian S; Roberts, Thomas M

    2014-01-01

    Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis. Live-cell and immunofluorescence studies showed that the majority of the PyST-expressing cells were arrested in prometaphase with almost no cells progressing beyond metaphase. These cells exhibited defects in chromosomal congression, sister chromatid cohesion and spindle positioning, resulting in the activation of the Spindle Assembly Checkpoint (SAC). Prolonged mitotic arrest then led to cell death via mitotic catastrophe. Cell cycle inhibitors that block cells in G1/S prevented PyST-induced death. PyST-induced cell death that occurs during M is not dependent on p53 status. These data suggested, and our results confirmed that, PP2A inhibition could be used to preferentially kill cancer cells with p53 mutations that proliferate normally in the presence of cell cycle inhibitors. PMID:24998850

  10. Polyoma small T antigen triggers cell death via mitotic catastrophe.

    PubMed

    Pores Fernando, A T; Andrabi, S; Cizmecioglu, O; Zhu, C; Livingston, D M; Higgins, J M G; Schaffhausen, B S; Roberts, T M

    2015-05-01

    Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis. Live-cell and immunofluorescence studies showed that the majority of the PyST expressing cells were arrested in prometaphase with almost no cells progressing beyond metaphase. These cells exhibited defects in chromosomal congression, sister chromatid cohesion and spindle positioning, thereby resulting in the activation of the spindle assembly checkpoint. Prolonged mitotic arrest then led to cell death via mitotic catastrophe. Cell cycle inhibitors that block cells in G1/S prevented PyST-induced death. PyST-induced cell death that occurs during M is not dependent on p53 status. These data suggested, and our results confirmed, that PP2A inhibition could be used to preferentially kill cancer cells with p53 mutations that proliferate normally in the presence of cell cycle inhibitors. PMID:24998850

  11. Incremental slow feature analysis: adaptive low-complexity slow feature updating from high-dimensional input streams.

    PubMed

    Kompella, Varun Raj; Luciw, Matthew; Schmidhuber, Jrgen

    2012-11-01

    We introduce here an incremental version of slow feature analysis (IncSFA), combining candid covariance-free incremental principal components analysis (CCIPCA) and covariance-free incremental minor components analysis (CIMCA). IncSFA's feature updating complexity is linear with respect to the input dimensionality, while batch SFA's (BSFA) updating complexity is cubic. IncSFA does not need to store, or even compute, any covariance matrices. The drawback to IncSFA is data efficiency: it does not use each data point as effectively as BSFA. But IncSFA allows SFA to be tractably applied, with just a few parameters, directly on high-dimensional input streams (e.g., visual input of an autonomous agent), while BSFA has to resort to hierarchical receptive-field-based architectures when the input dimension is too high. Further, IncSFA's updates have simple Hebbian and anti-Hebbian forms, extending the biological plausibility of SFA. Experimental results show IncSFA learns the same set of features as BSFA and can handle a few cases where BSFA fails. PMID:22845826

  12. Optimal Feature Selection in High-Dimensional Discriminant Analysis

    PubMed Central

    Kolar, Mladen; Liu, Han

    2014-01-01

    We consider the high-dimensional discriminant analysis problem. For this problem, different methods have been proposed and justified by establishing exact convergence rates for the classification risk, as well as the ?2 convergence results to the discriminative rule. However, sharp theoretical analysis for the variable selection performance of these procedures have not been established, even though model interpretation is of fundamental importance in scientific data analysis. This paper bridges the gap by providing sharp sufficient conditions for consistent variable selection using the sparse discriminant analysis (Mai et al., 2012). Through careful analysis, we establish rates of convergence that are significantly faster than the best known results and admit an optimal scaling of the sample size n, dimensionality p, and sparsity level s in the high-dimensional setting. Sufficient conditions are complemented by the necessary information theoretic limits on the variable selection problem in the context of high-dimensional discriminant analysis. Exploiting a numerical equivalence result, our method also establish the optimal results for the ROAD estimator (Fan et al., 2012) and the sparse optimal scaling estimator (Clemmensen et al., 2011). Furthermore, we analyze an exhaustive search procedure, whose performance serves as a benchmark, and show that it is variable selection consistent under weaker conditions. Extensive simulations demonstrating the sharpness of the bounds are also provided. PMID:25620807

  13. Evidence of Selection against Complex Mitotic-Origin Aneuploidy during Preimplantation Development

    PubMed Central

    McCoy, Rajiv C.; Demko, Zachary P.; Ryan, Allison; Banjevic, Milena; Hill, Matthew; Sigurjonsson, Styrmir; Rabinowitz, Matthew; Petrov, Dmitri A.

    2015-01-01

    Whole-chromosome imbalances affect over half of early human embryos and are the leading cause of pregnancy loss. While these errors frequently arise in oocyte meiosis, many such whole-chromosome abnormalities affecting cleavage-stage embryos are the result of chromosome missegregation occurring during the initial mitotic cell divisions. The first wave of zygotic genome activation at the 48 cell stage results in the arrest of a large proportion of embryos, the vast majority of which contain whole-chromosome abnormalities. Thus, the full spectrum of meiotic and mitotic errors can only be detected by sampling after the initial cell divisions, but prior to this selective filter. Here, we apply 24-chromosome preimplantation genetic screening (PGS) to 28,052 single-cell day-3 blastomere biopsies and 18,387 multi-cell day-5 trophectoderm biopsies from 6,366 in vitro fertilization (IVF) cycles. We precisely characterize the rates and patterns of whole-chromosome abnormalities at each developmental stage and distinguish errors of meiotic and mitotic origin without embryo disaggregation, based on informative chromosomal signatures. We show that mitotic errors frequently involve multiple chromosome losses that are not biased toward maternal or paternal homologs. This outcome is characteristic of spindle abnormalities and chaotic cell division detected in previous studies. In contrast to meiotic errors, our data also show that mitotic errors are not significantly associated with maternal age. PGS patients referred due to previous IVF failure had elevated rates of mitotic error, while patients referred due to recurrent pregnancy loss had elevated rates of meiotic error, controlling for maternal age. These results support the conclusion that mitotic error is the predominant mechanism contributing to pregnancy losses occurring prior to blastocyst formation. This high-resolution view of the full spectrum of whole-chromosome abnormalities affecting early embryos provides insight into the cytogenetic mechanisms underlying their formation and the consequences for human fertility. PMID:26491874

  14. Arsenite-induced mitotic death involves stress response and is independent of tubulin polymerization

    PubMed Central

    Taylor, B. Frazier; McNeely, Samuel C.; Miller, Heather L.; States, J. Christopher

    2008-01-01

    Arsenite, a known mitotic disruptor, causes cell cycle arrest and cell death at anaphase. The mechanism causing mitotic arrest is highly disputed. We compared arsenite to the spindle poisons nocodazole and paclitaxel. Immunofluorescence analysis of ?-tubulin in interphase cells demonstrated that, while nocodazole and paclitaxel disrupt microtubule polymerization through destabilization and hyperpolymerization, respectively, microtubules in arsenite-treated cells remain comparable to untreated cells even at supra-therapeutic concentrations. Immunofluorescence analysis of ?-tubulin in mitotic cells showed spindle formation in arsenite- and paclitaxel-treated cells but not in nocodazole-treated cells. Spindle formation in arsenite-treated cells appeared irregular and multi-polar. ?-tubulin staining showed that cells treated with nocodazole and therapeutic concentrations of paclitaxel contained two centrosomes. In contrast, most arsenite-treated mitotic cells contained more than two centrosomes, similar to centrosome abnormalities induced by heat shock. Of the three drugs tested, only arsenite treatment increased expression of the inducible isoform of heat shock protein 70 (HSP70i). HSP70 and HSP90 proteins are intimately involved in centrosome regulation and mitotic spindle formation. HSP90 inhibitor 17-DMAG sensitized cells to arsenite treatment and increased arsenite-induced centrosome abnormalities. Combined treatment of 17-DMAG and arsenite resulted in a supra-additive effect on viability, mitotic arrest, and centrosome abnormalities. Thus, arsenite-induced abnormal centrosome amplification and subsequent mitotic arrest is independent of effects on tubulin polymerization and may be due to specific stresses that are protected against by HSP90 and HSP70. PMID:18485433

  15. Arsenite-induced mitotic death involves stress response and is independent of tubulin polymerization

    SciTech Connect

    Taylor, B. Frazier; McNeely, Samuel C.; Miller, Heather L.; States, J. Christopher

    2008-07-15

    Arsenite, a known mitotic disruptor, causes cell cycle arrest and cell death at anaphase. The mechanism causing mitotic arrest is highly disputed. We compared arsenite to the spindle poisons nocodazole and paclitaxel. Immunofluorescence analysis of {alpha}-tubulin in interphase cells demonstrated that, while nocodazole and paclitaxel disrupt microtubule polymerization through destabilization and hyperpolymerization, respectively, microtubules in arsenite-treated cells remain comparable to untreated cells even at supra-therapeutic concentrations. Immunofluorescence analysis of {alpha}-tubulin in mitotic cells showed spindle formation in arsenite- and paclitaxel-treated cells but not in nocodazole-treated cells. Spindle formation in arsenite-treated cells appeared irregular and multi-polar. {gamma}-tubulin staining showed that cells treated with nocodazole and therapeutic concentrations of paclitaxel contained two centrosomes. In contrast, most arsenite-treated mitotic cells contained more than two centrosomes, similar to centrosome abnormalities induced by heat shock. Of the three drugs tested, only arsenite treatment increased expression of the inducible isoform of heat shock protein 70 (HSP70i). HSP70 and HSP90 proteins are intimately involved in centrosome regulation and mitotic spindle formation. HSP90 inhibitor 17-DMAG sensitized cells to arsenite treatment and increased arsenite-induced centrosome abnormalities. Combined treatment of 17-DMAG and arsenite resulted in a supra-additive effect on viability, mitotic arrest, and centrosome abnormalities. Thus, arsenite-induced abnormal centrosome amplification and subsequent mitotic arrest is independent of effects on tubulin polymerization and may be due to specific stresses that are protected against by HSP90 and HSP70.

  16. Clinical Risk Prediction by Exploring High-Order Feature Correlations

    PubMed Central

    Wang, Fei; Zhang, Ping; Wang, Xiang; Hu, Jianying

    2014-01-01

    Clinical risk prediction is one important problem in medical informatics, and logistic regression is one of the most widely used approaches for clinical risk prediction. In many cases, the number of potential risk factors is fairly large and the actual set of factors that contribute to the risk is small. Therefore sparse logistic regression is proposed, which can not only predict the clinical risk but also identify the set of relevant risk factors. The inputs of logistic regression and sparse logistic regression are required to be in vector form. This limits the applicability of these models in the problems when the data cannot be naturally represented vectors (e.g., medical images are two-dimensional matrices). To handle the cases when the data are in the form of multi-dimensional arrays, we propose HOSLR: High-Order Sparse Logistic Regression, which can be viewed as a high order extension of sparse logistic regression. Instead of solving one classification vector as in conventional logistic regression, we solve for K classification vectors in HOSLR (K is the number of modes in the data). A block proximal descent approach is proposed to solve the problem and its convergence is guaranteed. Finally we validate the effectiveness of HOSLR on predicting the onset risk of patients with Alzheimers disease and heart failure. PMID:25954428

  17. Micalastic high-voltage insulation: Design features and experience

    NASA Astrophysics Data System (ADS)

    Wichmann, A.

    1981-12-01

    High-quality mica, carefully selected epoxy resins and a well-matched vacuum/pressure impregnation process determine the characteristics of the MICALASTIC insulation for large turbine-generators. Logical development and process manufacturing quality control have led to an insulation system of high quality and operating reliability. The first winding of a turbine-generator being impregnated and cured under vacuum with solvent-free synthetic resin in 1958 was designed for 10.5 kV rated voltage. Ever since, Siemens AG and Kraftwerk Union AG have used this type of insulation for all direct-cooled windings and also for an increasing number of indirect-cooled windings. At present, 240 turbine-generators with a total of more than 115,000 MVA output have been built. Since 1960, this insulation system has been registered for Siemens AG under the trade name MICALASTIC. The stator windings of the largest, single-shaft generators to date, rated 1560 MVA, 27 kV, has been built with MICALASTIC insulation.

  18. Pair normalized channel feature and statistics-based learning for high-performance pedestrian detection

    NASA Astrophysics Data System (ADS)

    Zeng, Bobo; Wang, Guijin; Ruan, Zhiwei; Lin, Xinggang; Meng, Long

    2012-07-01

    High-performance pedestrian detection with good accuracy and fast speed is an important yet challenging task in computer vision. We design a novel feature named pair normalized channel feature (PNCF), which simultaneously combines and normalizes two channel features in image channels, achieving a highly discriminative power and computational efficiency. PNCF applies to both gradient channels and color channels so that shape and appearance information are described and integrated in the same feature. To efficiently explore the formidably large PNCF feature space, we propose a statistics-based feature learning method to select a small number of potentially discriminative candidate features, which are fed into the boosting algorithm. In addition, channel compression and a hybrid pyramid are employed to speed up the multiscale detection. Experiments illustrate the effectiveness of PNCF and its learning method. Our proposed detector outperforms the state-of-the-art on several benchmark datasets in both detection accuracy and efficiency.

  19. Unbiased feature selection in learning random forests for high-dimensional data.

    PubMed

    Nguyen, Thanh-Tung; Huang, Joshua Zhexue; Nguyen, Thuy Thi

    2015-01-01

    Random forests (RFs) have been widely used as a powerful classification method. However, with the randomization in both bagging samples and feature selection, the trees in the forest tend to select uninformative features for node splitting. This makes RFs have poor accuracy when working with high-dimensional data. Besides that, RFs have bias in the feature selection process where multivalued features are favored. Aiming at debiasing feature selection in RFs, we propose a new RF algorithm, called xRF, to select good features in learning RFs for high-dimensional data. We first remove the uninformative features using p-value assessment, and the subset of unbiased features is then selected based on some statistical measures. This feature subset is then partitioned into two subsets. A feature weighting sampling technique is used to sample features from these two subsets for building trees. This approach enables one to generate more accurate trees, while allowing one to reduce dimensionality and the amount of data needed for learning RFs. An extensive set of experiments has been conducted on 47 high-dimensional real-world datasets including image datasets. The experimental results have shown that RFs with the proposed approach outperformed the existing random forests in increasing the accuracy and the AUC measures. PMID:25879059

  20. Unbiased Feature Selection in Learning Random Forests for High-Dimensional Data

    PubMed Central

    Nguyen, Thanh-Tung; Huang, Joshua Zhexue; Nguyen, Thuy Thi

    2015-01-01

    Random forests (RFs) have been widely used as a powerful classification method. However, with the randomization in both bagging samples and feature selection, the trees in the forest tend to select uninformative features for node splitting. This makes RFs have poor accuracy when working with high-dimensional data. Besides that, RFs have bias in the feature selection process where multivalued features are favored. Aiming at debiasing feature selection in RFs, we propose a new RF algorithm, called xRF, to select good features in learning RFs for high-dimensional data. We first remove the uninformative features using p-value assessment, and the subset of unbiased features is then selected based on some statistical measures. This feature subset is then partitioned into two subsets. A feature weighting sampling technique is used to sample features from these two subsets for building trees. This approach enables one to generate more accurate trees, while allowing one to reduce dimensionality and the amount of data needed for learning RFs. An extensive set of experiments has been conducted on 47 high-dimensional real-world datasets including image datasets. The experimental results have shown that RFs with the proposed approach outperformed the existing random forests in increasing the accuracy and the AUC measures. PMID:25879059

  1. Mitotic inhibition of clathrin-mediated endocytosis

    PubMed Central

    Fielding, Andrew B.; Royle, Stephen J.

    2014-01-01

    Endocytosis and mitosis are fundamental processes in a cell’s life. Nearly fifty years of research suggest that these processes are linked and that endocytosis is shut down as cells undergo the early stages of mitosis. Precisely how this occurs at a molecular level is an open question. In this review, we summarize the early work characterizing the inhibition of clathrin-mediated endocytosis and discuss recent challenges to this established concept. We also set out four proposed mechanisms for the inhibition: mitotic phosphorylation of endocytic proteins, altered membrane tension, moonlighting of endocytic proteins and a mitotic spindle-dependent mechanism. Finally, we speculate the functional consequences of endocytic shutdown during mitosis and where an understanding of the mechanism of inhibition will lead us in the future. PMID:23307073

  2. Automatic microscopy for mitotic cell location.

    NASA Technical Reports Server (NTRS)

    Herron, J.; Ranshaw, R.; Castle, J.; Wald, N.

    1972-01-01

    Advances are reported in the development of an automatic microscope with which to locate hematologic or other cells in mitosis for subsequent chromosome analysis. The system under development is designed to perform the functions of: slide scanning to locate metaphase cells; conversion of images of selected cells into binary form; and on-line computer analysis of the digitized image for significant cytogenetic data. Cell detection criteria are evaluated using a test sample of 100 mitotic cells and 100 artifacts.

  3. Highly featured amorphous silicon nanorod arrays for high-performance lithium-ion batteries

    SciTech Connect

    Soleimani-Amiri, Samaneh; Safiabadi Tali, Seied Ali; Azimi, Soheil; Sanaee, Zeinab; Mohajerzadeh, Shamsoddin

    2014-11-10

    High aspect-ratio vertical structures of amorphous silicon have been realized using hydrogen-assisted low-density plasma reactive ion etching. Amorphous silicon layers with the thicknesses ranging from 0.5 to 10 μm were deposited using radio frequency plasma enhanced chemical vapor deposition technique. Standard photolithography and nanosphere colloidal lithography were employed to realize ultra-small features of the amorphous silicon. The performance of the patterned amorphous silicon structures as a lithium-ion battery electrode was investigated using galvanostatic charge-discharge tests. The patterned structures showed a superior Li-ion battery performance compared to planar amorphous silicon. Such structures are suitable for high current Li-ion battery applications such as electric vehicles.

  4. A study of directional instability during mitotic chromosome movement

    NASA Astrophysics Data System (ADS)

    Joglekar, Ajit P.

    Mitotic chromosome movements are responsible for the correct segregation of duplicated chromosomes into the daughter cells. Errors in this process are known to play a role in some of the serious diseases such as cancer, and the little understood process of aging. A thorough comprehension of the physical basis of this process is therefore necessary. An intriguing aspect of chromosome movements during mitosis is "directional instability": runs with approximately constant speed punctuated by abrupt reversal in direction of motion. I have constructed a mechanistic model that views chromosome movement as a result of interplay between poleward and antipoleward or polar ejection forces (PEF) on a chromosome; and microtubule (MT) depolymerization-coupled movement of the chromosome. Computer simulations based on this model using a single set of parameters accurately and quantitatively predict: the force, character, speed, and duration of chromosome movements, oscillations of chromosomes associated with only one spindle pole, the larger force during anaphase, the effect of MT-depolymerizing drugs on chromosome movements, and the decreased turnover of kinetochore-MTs during anaphase. The model also predicts how chromosome behavior should respond to perturbations of the PEF. These predictions could be unequivocally tested if it were possible to destroy structures smaller than the light resolution limit with minimal collateral damage. To address these requirements, I developed a methodology for ultrahigh resolution microsurgery with tightly-focused, ultrafast lasers pulses. This entailed an in-depth study of optical breakdown in dielectrics. Characterization of the single pulse damage in test dielectric materials ranging from silicon and glass to cell walls and membranes has shown that in the target regions where the laser intensity exceeds critical intensity, optical breakdown proceeds by tunneling ionization followed by a runaway avalanche ionization that ends with the ionization of all the valence electrons. Highly reproducible features on the nanometer size-scale indicate that the valence electron density is the central factor determining the critical intensity, implying that high precision can be maintained in a wide range of solids. Along with the new understanding optical breakdown, this technique will find potential applications in diverse fields ranging from MEMS fabrication to nano-fluidics, as well as cellular nanosurgery.

  5. DEK over-expression promotes mitotic defects and micronucleus formation.

    PubMed

    Matrka, Marie C; Hennigan, Robert F; Kappes, Ferdinand; DeLay, Monica L; Lambert, Paul F; Aronow, Bruce J; Wells, Susanne I

    2015-12-17

    The DEK gene encodes a nuclear protein that binds chromatin and is involved in various fundamental nuclear processes including transcription, RNA splicing, DNA replication and DNA repair. Several cancer types characteristically over-express DEK at the earliest stages of transformation. In order to explore relevant mechanisms whereby DEK supports oncogenicity, we utilized cancer databases to identify gene transcripts whose expression patterns are tightly correlated with that of DEK. We identified an enrichment of genes involved in mitosis and thus investigated the regulation and possible function of DEK in cell division. Immunofluorescence analyses revealed that DEK dissociates from DNA in early prophase and re-associates with DNA during telophase in human keratinocytes. Mitotic cell populations displayed a sharp reduction in DEK protein levels compared to the corresponding interphase population, suggesting DEK may be degraded or otherwise removed from the cell prior to mitosis. Interestingly, DEK overexpression stimulated its own aberrant association with chromatin throughout mitosis. Furthermore, DEK co-localized with anaphase bridges, chromosome fragments, and micronuclei, suggesting a specific association with mitotically defective chromosomes. We found that DEK over-expression in both non-transformed and transformed cells is sufficient to stimulate micronucleus formation. These data support a model wherein normal chromosomal clearance of DEK is required for maintenance of high fidelity cell division and chromosomal integrity. Therefore, the overexpression of DEK and its incomplete removal from mitotic chromosomes promotes genomic instability through the generation of genetically abnormal daughter cells. Consequently, DEK over-expression may be involved in the initial steps of developing oncogenic mutations in cells leading to cancer initiation. PMID:25945971

  6. Mitotic spindle studied using picosecond laser scissors

    NASA Astrophysics Data System (ADS)

    Baker, N. M.; Botvinick, E. L.; Shi, Linda; Berns, M. B.; Wu, George

    2006-08-01

    In previous studies we have shown that the second harmonic 532 nm, from a picosecond frequency doubled Nd:YAG laser, can cleanly and selectively disrupt spindle fiber microtubules in live cells (Botvinick et al 2004, Biophys. J. 87:4303-4212). In the present study we have ablated different locations and amounts of the metaphase mitotic spindle, and followed the cells in order to observe the fate of the irradiated spindle and the ability of the cell to continue through mitosis. Cells of the rat kangaroo line (PTK2) were stably transfected by ECFP-tubulin and, using fluorescent microscopy and the automated RoboLase microscope, (Botvinick and Berns, 2005, Micros. Res. Tech. 68:65-74) brightly fluorescent individual cells in metaphase were irradiated with 0.2447 nJ/micropulse corresponding to an irradiance of 1.4496*10^7 J/(ps*cm^2) . Upon irradiation the exposed part of the mitotic spindle immediately lost fluorescence and the following events were observed in the cells over time: (1) immediate contraction of the spindle pole towards the cut, (2) recovery of connection between pole and cut microtubule, (3) completion of mitosis. This system should be very useful in studying internal cellular dynamics of the mitotic spindle.

  7. Design features for high peak-load availability in cogeneration plants

    SciTech Connect

    Shor, S.W.W.

    1987-07-01

    High availability during periods of utility peak loads can be important to a cogeneration plant. Design features supporting high availability in both conventional steam-electric and gas-turbine-based cogeneration plants are described.

  8. Inhibition of glycogen synthase kinase-3 beta induces apoptosis and mitotic catastrophe by disrupting centrosome regulation in cancer cells

    PubMed Central

    Yoshino, Yuki; Ishioka, Chikashi

    2015-01-01

    Glycogen synthase kinase-3 beta (GSK-3?) has been investigated as a therapeutic target for numerous human diseases including cancer because of their diverse cellular functions. Although GSK-3? inhibitors have been investigated as anticancer reagents, precise biological mechanisms remain to be determined. In this study, we investigated the anticancer effects of GSK-3? inhibitors on cancer cell lines and observed centrosome dysregulation which resulted in abnormal mitosis. Mitotic checkpoints sensed the mitotic abnormalities and induced apoptosis. For cells that were inherently resistant to apoptosis, cell death distinct from apoptosis was induced. After GSK-3? inhibitor treatment, these cells exhibited characteristic features of mitotic catastrophe, including distended and multivesiculated nuclei and inappropriate reductions in cyclin B1 expression. This suggested that mitotic catastrophe was an alternative mechanism in cells resistant to apoptosis. Although the role of GSK-3? in centrosomes has not yet been clarified, phosphorylated GSK-3? was localised in centrosomes. From these data, GSK-3? seems to regulate centrosome function. Thus, we propose that centrosome dysregulation is an important mechanism for the anticancer effects of GSK-3? inhibitors and that mitotic catastrophe serves as a safe-guard system to remove cells with any mitotic abnormalities induced by GSK-3? inhibition. PMID:26292722

  9. Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitotic catastrophe

    PubMed Central

    Li, Jingjing; Hong, Myung Jin; Chow, Jeremy P.H.; Man, Wing Yu; Mak, Joyce P.Y.; Ma, Hoi Tang; Poon, Randy Y.C.

    2015-01-01

    Mitosis is choreographed by a number of protein kinases including polo-like kinases and Aurora kinases. As these kinases are frequently dysregulated in cancers, small-molecule inhibitors have been developed for targeted anticancer therapies. Given that PLK1 and Aurora kinases possess both unique functions as well as co-regulate multiple mitotic events, whether pharmacological inhibition of these kinases together can enhance mitotic catastrophe remains an outstanding issue to be determined. Using concentrations of inhibitors that did not induce severe mitotic defects on their own, we found that both the metaphase arrest and mitotic slippage induced by inhibitors targeting Aurora A and Aurora B (MK-5108 and Barasertib respectively) were enhanced by a PLK1 inhibitor (BI 2536). We found that PLK1 is overexpressed in cells from nasopharyngeal carcinoma, a highly invasive cancer with poor prognosis, in comparison to normal nasopharyngeal epithelial cells. Nasopharyngeal carcinoma cells were more sensitive to BI 2536 as a single agent and co-inhibition with Aurora kinases than normal cells. These observations underscore the mechanism and potential benefits of targeting PLK1 and Aurora kinases to induce mitotic catastrophe in cancer cells. PMID:25871386

  10. Using in Vivo Biotinylated Ubiquitin to Describe a Mitotic Exit Ubiquitome from Human Cells *

    PubMed Central

    Min, Mingwei; Mayor, Ugo; Dittmar, Gunnar; Lindon, Catherine

    2014-01-01

    Mitotic division requires highly regulated morphological and biochemical changes to the cell. Upon commitment to exit mitosis, cells begin to remove mitotic regulators in a temporally and spatially controlled manner to bring about the changes that reestablish interphase. Ubiquitin-dependent pathways target these regulators to generate polyubiquitin-tagged substrates for degradation by the 26S proteasome. However, the lack of cell-based assays to investigate in vivo ubiquitination limits our knowledge of the identity of substrates of ubiquitin-mediated regulation in mitosis. Here we report an in vivo ubiquitin tagging system used in human cells that allows efficient purification of ubiquitin conjugates from synchronized cell populations. Coupling purification with mass spectrometry, we have identified a series of mitotic regulators targeted for polyubiquitination in mitotic exit. We show that some are new substrates of the anaphase-promoting complex/cyclosome and validate KIFC1 and RacGAP1/Cyk4 as two such targets involved respectively in timely mitotic spindle disassembly and cell spreading. We conclude that in vivo biotin tagging of ubiquitin can provide valuable information about the role of ubiquitin-mediated regulation in processes required for rebuilding interphase cells. PMID:24857844

  11. Dietary flavonoid fisetin induces a forced exit from mitosis by targeting the mitotic spindle checkpoint

    PubMed Central

    Salmela, Anna-Leena; Pouwels, Jeroen; Varis, Asta; Kukkonen, Anu M.; Toivonen, Pauliina; Halonen, Pasi K.; Perälä, Merja; Kallioniemi, Olli; Gorbsky, Gary J.; Kallio, Marko J.

    2009-01-01

    Fisetin is a natural flavonol present in edible vegetables, fruits and wine at 2–160 μg/g concentrations and an ingredient in nutritional supplements with much higher concentrations. The compound has been reported to exert anticarcinogenic effects as well as antioxidant and anti-inflammatory activity via its ability to act as an inhibitor of cell proliferation and free radical scavenger, respectively. Our cell-based high-throughput screen for small molecules that override chemically induced mitotic arrest identified fisetin as an antimitotic compound. Fisetin rapidly compromised microtubule drug-induced mitotic block in a proteasome-dependent manner in several human cell lines. Moreover, in unperturbed human cancer cells fisetin caused premature initiation of chromosome segregation and exit from mitosis without normal cytokinesis. To understand the molecular mechanism behind these mitotic errors, we analyzed the consequences of fisetin treatment on the localization and phoshorylation of several mitotic proteins. Aurora B, Bub1, BubR1 and Cenp-F rapidly lost their kinetochore/centromere localization and others became dephosphorylated upon addition of fisetin to the culture medium. Finally, we identified Aurora B kinase as a novel direct target of fisetin. The activity of Aurora B was significantly reduced by fisetin in vitro and in cells, an effect that can explain the observed forced mitotic exit, failure of cytokinesis and decreased cell viability. In conclusion, our data propose that fisetin perturbs spindle checkpoint signaling, which may contribute to the antiproliferative effects of the compound. PMID:19395653

  12. Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitotic catastrophe.

    PubMed

    Li, Jingjing; Hong, Myung Jin; Chow, Jeremy P H; Man, Wing Yu; Mak, Joyce P Y; Ma, Hoi Tang; Poon, Randy Y C

    2015-04-20

    Mitosis is choreographed by a number of protein kinases including polo-like kinases and Aurora kinases. As these kinases are frequently dysregulated in cancers, small-molecule inhibitors have been developed for targeted anticancer therapies. Given that PLK1 and Aurora kinases possess both unique functions as well as co-regulate multiple mitotic events, whether pharmacological inhibition of these kinases together can enhance mitotic catastrophe remains an outstanding issue to be determined. Using concentrations of inhibitors that did not induce severe mitotic defects on their own, we found that both the metaphase arrest and mitotic slippage induced by inhibitors targeting Aurora A and Aurora B (MK-5108 and Barasertib respectively) were enhanced by a PLK1 inhibitor (BI 2536). We found that PLK1 is overexpressed in cells from nasopharyngeal carcinoma, a highly invasive cancer with poor prognosis, in comparison to normal nasopharyngeal epithelial cells. Nasopharyngeal carcinoma cells were more sensitive to BI 2536 as a single agent and co-inhibition with Aurora kinases than normal cells. These observations underscore the mechanism and potential benefits of targeting PLK1 and Aurora kinases to induce mitotic catastrophe in cancer cells. PMID:25871386

  13. Non-iridescent Transmissive Structural Color Filter Featuring Highly Efficient Transmission and High Excitation Purity

    PubMed Central

    Shrestha, Vivek Raj; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2014-01-01

    Nanostructure based color filtering has been considered an attractive replacement for current colorant pigmentation in the display technologies, in view of its increased efficiencies, ease of fabrication and eco-friendliness. For such structural filtering, iridescence relevant to its angular dependency, which poses a detrimental barrier to the practical development of high performance display and sensing devices, should be mitigated. We report on a non-iridescent transmissive structural color filter, fabricated in a large area of 76.2 25.4?mm2, taking advantage of a stack of three etalon resonators in dielectric films based on a high-index cavity in amorphous silicon. The proposed filter features a high transmission above 80%, a high excitation purity of 0.93 and non-iridescence over a range of 160, exhibiting no significant change in the center wavelength, dominant wavelength and excitation purity, which implies no change in hue and saturation of the output color. The proposed structure may find its potential applications to large-scale display and imaging sensor systems. PMID:24815530

  14. Non-iridescent Transmissive Structural Color Filter Featuring Highly Efficient Transmission and High Excitation Purity

    NASA Astrophysics Data System (ADS)

    Shrestha, Vivek Raj; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

    2014-05-01

    Nanostructure based color filtering has been considered an attractive replacement for current colorant pigmentation in the display technologies, in view of its increased efficiencies, ease of fabrication and eco-friendliness. For such structural filtering, iridescence relevant to its angular dependency, which poses a detrimental barrier to the practical development of high performance display and sensing devices, should be mitigated. We report on a non-iridescent transmissive structural color filter, fabricated in a large area of 76.2 25.4 mm2, taking advantage of a stack of three etalon resonators in dielectric films based on a high-index cavity in amorphous silicon. The proposed filter features a high transmission above 80%, a high excitation purity of 0.93 and non-iridescence over a range of 160, exhibiting no significant change in the center wavelength, dominant wavelength and excitation purity, which implies no change in hue and saturation of the output color. The proposed structure may find its potential applications to large-scale display and imaging sensor systems.

  15. Microtubule-dependent regulation of mitotic protein degradation

    PubMed Central

    Song, Ling; Craney, Allison; Rape, Michael

    2014-01-01

    Accurate cell division depends on tightly regulated ubiquitylation events catalyzed by the anaphase-promoting complex. Among its many substrates, the APC/C triggers the degradation of proteins that stabilize the mitotic spindle, and loss or accumulation of such spindle assembly factors can result in aneuploidy and cancer. Although critical for cell division, it has remained poorly understood how the timing of spindle assembly factor degradation is established during mitosis. Here, we report that active spindle assembly factors are protected from APC/C-dependent degradation by microtubules. In contrast, those molecules that are not bound to microtubules are highly susceptible to proteolysis and turned over immediately after APC/C-activation. The correct timing of spindle assembly factor degradation, as achieved by this regulatory circuit, is required for accurate spindle structure and function. We propose that the localized stabilization of APC/C-substrates provides a mechanism for the selective disposal of cell cycle regulators that have fulfilled their mitotic roles. PMID:24462202

  16. Differential Mitotic Stability of Yeast Disomes Derived from Triploid Meiosis

    PubMed Central

    Campbell, Douglas; Doctor, John S.; Feuersanger, Jeane H.; Doolittle, Mark M.

    1981-01-01

    The frequencies of recovered disomy among the meiotic segregants of yeast (Saccharomyces cerevisiae) triploids were assessed under conditions in which all 17 yeast chromosomes were monitored simultaneously. The studies employed inbred triploids, in which all homologous centromeres were identical by descent, and single haploid testers carrying genetic markers for all 17 linkage groups. The principal results include: (1) Ascospores from triploid meiosis germinate at frequencies comparable to those from normal diploids, but most fail to produce visible colonies due to the growth-retarding effects of high multiple disomy. (2) The probability of disome formation during triploid meiosis is the same for all chromosomes; disomy for any given chromosome does not exclude simultaneous disomy for any other chromosome. (3) The 17 yeast chromosomes fall into three frequency classes in terms of disome recovery. The results support the idea that multiply disomic meiotic segregants of the triploid experience repeated, nonrandom, post-germination mitotic chromosome losses (N+1→N) and that the observed variations in individual disome recovery are wholly attributable to inherent differences in disome mitotic stability. PMID:7035289

  17. INFUSE: Interactive Feature Selection for Predictive Modeling of High Dimensional Data.

    PubMed

    Krause, Josua; Perer, Adam; Bertini, Enrico

    2014-12-01

    Predictive modeling techniques are increasingly being used by data scientists to understand the probability of predicted outcomes. However, for data that is high-dimensional, a critical step in predictive modeling is determining which features should be included in the models. Feature selection algorithms are often used to remove non-informative features from models. However, there are many different classes of feature selection algorithms. Deciding which one to use is problematic as the algorithmic output is often not amenable to user interpretation. This limits the ability for users to utilize their domain expertise during the modeling process. To improve on this limitation, we developed INFUSE, a novel visual analytics system designed to help analysts understand how predictive features are being ranked across feature selection algorithms, cross-validation folds, and classifiers. We demonstrate how our system can lead to important insights in a case study involving clinical researchers predicting patient outcomes from electronic medical records. PMID:26356875

  18. Global Phosphoproteomic Mapping of Early Mitotic Exit in Human Cells Identifies Novel Substrate Dephosphorylation Motifs.

    PubMed

    McCloy, Rachael A; Parker, Benjamin L; Rogers, Samuel; Chaudhuri, Rima; Gayevskiy, Velimir; Hoffman, Nolan J; Ali, Naveid; Watkins, D Neil; Daly, Roger J; James, David E; Lorca, Thierry; Castro, Anna; Burgess, Andrew

    2015-08-01

    Entry into mitosis is driven by the coordinated phosphorylation of thousands of proteins. For the cell to complete mitosis and divide into two identical daughter cells it must regulate dephosphorylation of these proteins in a highly ordered, temporal manner. There is currently a lack of a complete understanding of the phosphorylation changes that occur during the initial stages of mitotic exit in human cells. Therefore, we performed a large unbiased, global analysis to map the very first dephosphorylation events that occur as cells exit mitosis. We identified and quantified the modification of >16,000 phosphosites on >3300 unique proteins during early mitotic exit, providing up to eightfold greater resolution than previous studies. The data have been deposited to the ProteomeXchange with identifier PXD001559. Only a small fraction (? 10%) of phosphorylation sites were dephosphorylated during early mitotic exit and these occurred on proteins involved in critical early exit events, including organization of the mitotic spindle, the spindle assembly checkpoint, and reformation of the nuclear envelope. Surprisingly this enrichment was observed across all kinase consensus motifs, indicating that it is independent of the upstream phosphorylating kinase. Therefore, dephosphorylation of these sites is likely determined by the specificity of phosphatase/s rather than the activity of kinase/s. Dephosphorylation was significantly affected by the amino acids at and surrounding the phosphorylation site, with several unique evolutionarily conserved amino acids correlating strongly with phosphorylation status. These data provide a potential mechanism for the specificity of phosphatases, and how they co-ordinate the ordered events of mitotic exit. In summary, our results provide a global overview of the phosphorylation changes that occur during the very first stages of mitotic exit, providing novel mechanistic insight into how phosphatase/s specifically regulate this critical transition. PMID:26055452

  19. Kinesin 6 family member Subito participates in mitotic spindle assembly and interacts with mitotic regulators.

    PubMed

    Cesario, Jeff M; Jang, Janet K; Redding, Bethany; Shah, Nishit; Rahman, Taslima; McKim, Kim S

    2006-11-15

    Drosophila Subito is a kinesin 6 family member and ortholog of mitotic kinesin-like protein (MKLP2) in mammalian cells. Based on the previously established requirement for Subito in meiotic spindle formation and for MKLP2 in cytokinesis, we investigated the function of Subito in mitosis. During metaphase, Subito localized to microtubules at the center of the mitotic spindle, probably interpolar microtubules that originate at the poles and overlap in antiparallel orientation. Consistent with this localization pattern, subito mutants improperly assembled microtubules at metaphase, causing activation of the spindle assembly checkpoint and lagging chromosomes at anaphase. These results are the first demonstration of a kinesin 6 family member with a function in mitotic spindle assembly, possibly involving the interpolar microtubules. However, the role of Subito during mitotic anaphase resembles other kinesin 6 family members. Subito localizes to the spindle midzone at anaphase and is required for the localization of Polo, Incenp and Aurora B. Genetic evidence suggested that the effects of subito mutants are attenuated as a result of redundant mechanisms for spindle assembly and cytokinesis. For example, subito double mutants with ncd, polo, Aurora B or Incenp mutations were synthetic lethal with severe defects in microtubule organization. PMID:17077127

  20. Grading of Well-differentiated Pancreatic Neuroendocrine Tumors Is Improved by the Inclusion of Both Ki67 Proliferative Index and Mitotic Rate

    PubMed Central

    McCall, Chad M.; Shi, Chanjuan; Cornish, Toby C.; Klimstra, David S.; Tang, Laura H.; Basturk, Olca; Mun, Liew Jun; Ellison, Trevor A.; Wolfgang, Christopher L.; Choti, Michael A.; Schulick, Richard D.; Edil, Barish H.; Hruban, Ralph H.

    2013-01-01

    The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010 by the World Health Organization (WHO) mandates the use of both mitotic rate and Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In cases when these measures are not concordant for grade, it is recommended to assign the higher grade, but specific data justifying this approach do not exist. Thus, we counted mitotic figures and immunolabeled, using the Ki67 antibody, 297 WHO mitotic grade 1 and 2 PanNETs surgically resected at a single institution. We quantified the Ki67 proliferative index by marking at least 500 cells in hot spots and by using digital image analysis software to count each marked positive/negative cell and then compared the results with histologic features and overall survival. Of 264 WHO mitotic grade 1 PanNETs, 33% were WHO grade 2 by Ki67 proliferative index. Compared with concordant grade 1 tumors, grade-discordant tumors were more likely to have metastases to lymph node (56% vs. 34%) (P < 0.01) and to distant sites (46% vs. 12%) (P < 0.01). Discordant mitotic grade 1 PanNETs also showed statistically significantly more infiltrative growth patterns, perineural invasion, and small vessel invasion. Overall survival was significantly different (P < 0.01), with discordant mitotic grade 1 tumors showing a median survival of 12 years compared with 16.7 years for concordant grade 1 tumors. Conversely, mitotic grade 1/Ki67 grade 2 PanNETs showed few significant differences from tumors that were mitotic grade 2 and either Ki67 grade 1 or 2. Our data demonstrate that mitotic rate and Ki67-based grades of PanNETs are often discordant, and when the Ki67 grade is greater than the mitotic grade, clinical outcomes and histopathologic features are significantly worse than concordant grade 1 tumors. Patients with discordant mitotic grade 1/Ki67 grade 2 tumors have shorter overall survival and larger tumors with more metastases and more aggressive histologic features. These data strongly suggest that Ki67 labeling be performed on all PanNETs in addition to mitotic rate determination to define more accurately tumor grade and prognosis. PMID:24121170

  1. Post-slippage multinucleation renders cytotoxic variation in anti-mitotic drugs that target the microtubules or mitotic spindle

    PubMed Central

    Zhu, Yanting; Zhou, Yuan; Shi, Jue

    2014-01-01

    One common cancer chemotherapeutic strategy is to perturb cell division with anti-mitotic drugs. Paclitaxel, the classic microtubule-targeting anti-mitotic drug, so far still outperforms the newer, more spindle-specific anti-mitotics in the clinic, but the underlying cellular mechanism is poorly understood. In this study we identified post-slippage multinucleation, which triggered extensive DNA damage and apoptosis after drug-induced mitotic slippage, contributes to the extra cytotoxicity of paclitaxel in comparison to the spindle-targeting drug, Kinesin-5 inhibitor. Based on quantitative single-cell microscopy assays, we showed that attenuation of the degree of post-slippage multinucleation significantly reduced DNA damage and apoptosis in response to paclitaxel, and that post-slippage apoptosis was likely mediated by the p53-dependent DNA damage response pathway. Paclitaxel appeared to act as a double-edge sword, capable of killing proliferating cancer cells both during mitotic arrest and after mitotic slippage by inducing DNA damage. Our results thus suggest that to predict drug response to paclitaxel and anti-mitotics in general, 2 distinct sets of bio-markers, which regulate mitotic and post-slippage cytotoxicity, respectively, may need to be considered. Our findings provide important new insight not only for elucidating the cytotoxic mechanisms of paclitaxel, but also for understanding the variable efficacy of different anti-mitotic chemotherapeutics. PMID:24694730

  2. Using high spectral resolution spectrophotometry to study broad mineral absorption features on Mars

    NASA Technical Reports Server (NTRS)

    Blaney, D. L.; Crisp, D.

    1993-01-01

    Traditionally telescopic measurements of mineralogic absorption features have been made using relatively low to moderate (R=30-300) spectral resolution. Mineralogic absorption features tend to be broad so high resolution spectroscopy (R greater than 10,000) does not provide significant additional compositional information. Low to moderate resolution spectroscopy allows an observer to obtain data over a wide wavelength range (hundreds to thousands of wavenumbers) compared to the several wavenumber intervals that are collected using high resolution spectrometers. However, spectrophotometry at high resolution has major advantages over lower resolution spectroscopy in situations that are applicable to studies of the Martian surface, i.e., at wavelengths where relatively weak surface absorption features and atmospheric gas absorption features both occur.

  3. Mitotic recombination of chromosome 17 in astrocytomas

    SciTech Connect

    James, C.D.; Carlbom, E.; Nordenskjold, M.; Collins, V.P.; Cavenee, W.K. )

    1989-04-01

    Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.

  4. Induction of mitotic aneuploidy in lower eukaryotes

    SciTech Connect

    Kappas, A.

    1993-12-31

    Genetic tests for induction of mitotic aneuploidy in lower eukarotes used mainly the fungal systems of Aspergillus nidulans and Saccharomyces cerevisiae. There are several differences between the two systems such as the greater tolerance for aneuploidy and the fertility of triploids in S. cerevisiae, the stability of diploids and the selective advantage of haploids over diploids in Aspergillus and the mycelial growth of Aspergillus. On the other hand several similarities also exist between the two systems such as the general instability and varying growth rate of disomics and the random loss of extra chromosomes which produces more competitive types or the most frequent recovery of certain specific aneuploids. In using lower eukaryotes as test systems for the identification of aneugens several points should be considered which concern the relevance of such systems to higher organisms, the ability to identify primary aneuploidy and distinguish this from events, such as chromosomal breaks, which lead to secondary aneuploidy and the ability to obtain repeatable results. Within the framework of an EEC comparative study for evaluating assays for aneuploidy, a number of chemicals were assayed in A. nidulans for mitotic instability due to malsegregation of chromosomes at cell division.

  5. The transforming acidic coiled coil 3 protein is essential for spindle-dependent chromosome alignment and mitotic survival.

    PubMed

    Schneider, Leonid; Essmann, Frank; Kletke, Anja; Rio, Paula; Hanenberg, Helmut; Wetzel, Wiebke; Schulze-Osthoff, Klaus; Nürnberg, Bernd; Piekorz, Roland P

    2007-10-01

    Cancer-associated centrosomal transforming acidic coiled coil (TACC) proteins are involved in mitotic spindle function. By employing gene targeting, we have recently described a nonredundant and essential role of TACC3 in regulating cell proliferation. In this study, we used an inducible RNA interference approach to characterize the molecular function of TACC3 and its role in mitotic progression and cell survival. Our data demonstrate that a TACC3 knockdown arrests G(1) checkpoint-compromised HeLa cells prior to anaphase with aberrant spindle morphology and severely misaligned chromosomes. Interestingly, TACC3-depleted cells fail to accumulate the mitotic kinase Aurora B and the checkpoint protein BubR1 to normal levels at kinetochores. Moreover, localization of the structural protein Ndc80 at outer kinetochores is reduced, indicating a defective kinetochore-microtubule attachment in TACC3-deficient cells. As a consequence of prolonged TACC3 depletion, cells undergo caspase-dependent cell death that relies on a spindle checkpoint-dependent mitotic arrest. TACC3 knockdown cells that escape from this arrest by mitotic slippage become highly polyploid and accumulate supernumerary centrosomes. Similarly, deficiency of the post-mitotic cell cycle inhibitor p21(WAF) exacerbates the effects of TACC3 depletion. Our findings therefore point to an essential role of TACC3 in spindle assembly and cellular survival and identify TACC3 as a potential therapeutic target in cancer cells. PMID:17675670

  6. Hybrid feature detection and information accumulation using high-resolution LC-MS metabolomics data.

    PubMed

    Yu, Tianwei; Park, Youngja; Li, Shuzhao; Jones, Dean P

    2013-03-01

    Feature detection is a critical step in the preprocessing of liquid chromatography-mass spectrometry (LC-MS) metabolomics data. Currently, the predominant approach is to detect features using noise filters and peak shape models based on the data at hand alone. Databases of known metabolites and historical data contain information that could help boost the sensitivity of feature detection, especially for low-concentration metabolites. However, utilizing such information in targeted feature detection may cause large number of false positives because of the high levels of noise in LC-MS data. With high-resolution mass spectrometry such as liquid chromatograph-Fourier transform mass spectrometry (LC-FTMS), high-confidence matching of peaks to known features is feasible. Here we describe a computational approach that serves two purposes. First it boosts feature detection sensitivity by using a hybrid procedure of both untargeted and targeted peak detection. New algorithms are designed to reduce the chance of false-positives by nonparametric local peak detection and filtering. Second, it can accumulate information on the concentration variation of metabolites over large number of samples, which can help find rare features and/or features with uncommon concentration in future studies. Information can be accumulated on features that are consistently found in real data even before their identities are found. We demonstrate the value of the approach in a proof-of-concept study. The method is implemented as part of the R package apLCMS at http://www.sph.emory.edu/apLCMS/ . PMID:23362826

  7. Pioneering barren land: mitotic bookmarking by transcription factors.

    PubMed

    Rada-Iglesias, Alvaro

    2013-02-25

    Genome condensation during mitosis presents a chromatin landscape largely inaccessible to RNA polymerase II and most transcription factors. Caravaca et al. (2013) now report in Genes and Development that the pioneer transcription factor FOXA1 is retained at mitotic chromosomes, bookmarking the genome to enable gene expression reestablishment upon mitotic exit. PMID:23449470

  8. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells

    PubMed Central

    Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J

    2014-01-01

    Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC. Ablation of MELK selectively impairs proliferation of basal-like, but not luminal breast cancer cells both in vitro and in vivo. Mechanistically, depletion of MELK in BBC cells induces caspase-dependent cell death, preceded by defective mitosis. Finally, we find that Melk is not required for mouse development and physiology. Together, these data indicate that MELK is a normally non-essential kinase, but is critical for BBC and thus represents a promising selective therapeutic target for the most aggressive subtype of breast cancer. DOI: http://dx.doi.org/10.7554/eLife.01763.001 PMID:24844244

  9. Identification of consensus motifs associated with mitotic recombination and clinical characteristics in patients with paternal uniparental isodisomy of chromosome 11.

    PubMed

    Ohtsuka, Yasufumi; Higashimoto, Ken; Oka, Takehiko; Yatsuki, Hitomi; Jozaki, Kosuke; Maeda, Toshiyuki; Kawahara, Kozo; Hamasaki, Yuhei; Matsuo, Muneaki; Nishioka, Kenichi; Joh, Keiichiro; Mukai, Tsunehiro; Soejima, Hidenobu

    2016-04-01

    Uniparental disomy (UPD) is defined as the inheritance of both homologs of a given genomic region from only one parent. The majority of UPD includes an entire chromosome. However, the extent of UPD is sometimes limited to a subchromosomal region (segmental UPD). Mosaic paternal UPD (pUPD) of chromosome 11 is found in approximately 20% of patients with Beckwith-Wiedemann syndrome (BWS) and almost all pUPDs are segmental isodisomic pUPDs resulting from mitotic recombination at an early embryonic stage. A mechanism initiating a DNA double strand break (DSB) within 11p has been predicted to lead to segmental pUPD. However, no consensus motif has yet been found. Here, we analyzed 32 BWS patients with pUPD by SNP array and searched for consensus motifs. We identified four consensus motifs frequently appearing within breakpoint regions of segmental pUPD. These motifs were found in another nine BWS patients with pUPD. In addition, the seven motifs found in meiotic recombination hot spots could not be found within pUPD breakpoint regions. Histone H3 lysine 4 trimethylation, a marker of DSB initiation, could not be found either. These findings suggest that the mechanism(s) of mitotic recombination leading to segmental pUPD are different from that of meiotic recombination. Furthermore, we found seven patients with paternal uniparental diploidy (PUD) mosaicism. Comparison of clinical features between segmental pUPDs and PUDs showed that developmental disability and cardiac abnormalities were additional characteristic features of PUD mosaicism, along with high risk of tumor development. We also found that macroglossia was characteristic of segmental pUPD mosaicism. PMID:26908620

  10. Random mitotic activities across human embryonic stem cell colonies.

    SciTech Connect

    Jin, Q.; Duggan, R.; Dasa, S.; Li, F.; Chen, L.

    2010-08-01

    A systemic and quantitative study was performed to examine whether different levels of mitotic activities, assessed by the percentage of S-phase cells at any given time point, existed at different physical regions of human embryonic stem (hES) cell colonies at 2, 4, 6 days after cell passaging. Mitotically active cells were identified by the positive incorporation of 5-bromo-2-deoxyuridine (BrdU) within their newly synthesized DNA. Our data indicated that mitotically active cells were often distributed as clusters randomly across the colonies within the examined growth period, presumably resulting from local deposition of newly divided cells. This latter notion was further demonstrated by the confined growth of enhanced green florescence protein (EGFP) expressing cells amongst non-GFP expressing cells. Furthermore, the overall percentage of mitotically active cells remained constantly at about 50% throughout the 6-day culture period, indicating mitotic activities of hES cell cultures were time-independent under current growth conditions.

  11. A new role for Rab GTPases during early mitotic stages.

    PubMed

    Das, Sanchaita; Hehnly, Heidi; Doxsey, Stephen

    2014-01-01

    A recent study revealed new roles for the Rab11 GTPase during mitosis. Rab11 is involved in recycling endosome localization to mitotic spindle poles via dynein-mediated transport. This process is in contrast to Golgi membranes, which disperse in mitosis and do not appear to directly contribute to mitotic functions. Rab11-depletion prevents recycling endosome organization at spindle poles, delays mitotic progression, and disrupts spindle pole protein recruitment, astral microtubule organization, and mitotic spindle orientation. However, Rab11 is not the only endocytic and/or trafficking protein that regulates mitotic progression. Clathrin and two small GTPases (Rab6A', Rab5) play key roles in spindle organization and function. In this commentary, we discuss the roles of all these canonical endocytic and membrane trafficking proteins during mitosis and speculate on possible cross-communication between them and their molecular pathways that ensure faithful progression through mitosis. PMID:24921241

  12. A new role for Rab GTPases during early mitotic stages

    PubMed Central

    Das, Sanchaita; Hehnly, Heidi; Doxsey, Stephen

    2014-01-01

    A recent study revealed new roles for the Rab11 GTPase during mitosis. Rab11 is involved in recycling endosome localization to mitotic spindle poles via dynein-mediated transport. This process is in contrast to Golgi membranes, which disperse in mitosis and do not appear to directly contribute to mitotic functions. Rab11-depletion prevents recycling endosome organization at spindle poles, delays mitotic progression, and disrupts spindle pole protein recruitment, astral microtubule organization, and mitotic spindle orientation. However, Rab11 is not the only endocytic and/or trafficking protein that regulates mitotic progression. Clathrin and two small GTPases (Rab6A’, Rab5) play key roles in spindle organization and function. In this commentary, we discuss the roles of all these canonical endocytic and membrane trafficking proteins during mitosis and speculate on possible cross-communication between them and their molecular pathways that ensure faithful progression through mitosis. PMID:24921241

  13. Mitotic catastrophe occurs in the absence of apoptosis in p53-null cells with a defective G1 checkpoint.

    PubMed

    Fragkos, Michalis; Beard, Peter

    2011-01-01

    Cell death occurring during mitosis, or mitotic catastrophe, often takes place in conjunction with apoptosis, but the conditions in which mitotic catastrophe may exhibit features of programmed cell death are still unclear. In the work presented here, we studied mitotic cell death by making use of a UV-inactivated parvovirus (adeno-associated virus; AAV) that has been shown to induce a DNA damage response and subsequent death of p53-defective cells in mitosis, without affecting the integrity of the host genome. Osteosarcoma cells (U2OSp53DD) that are deficient in p53 and lack the G1 cell cycle checkpoint respond to AAV infection through a transient G2 arrest. We found that the infected U2OSp53DD cells died through mitotic catastrophe with no signs of chromosome condensation or DNA fragmentation. Moreover, cell death was independent of caspases, apoptosis-inducing factor (AIF), autophagy and necroptosis. These findings were confirmed by time-lapse microscopy of cellular morphology following AAV infection. The assays used readily revealed apoptosis in other cell types when it was indeed occurring. Taken together the results indicate that in the absence of the G1 checkpoint, mitotic catastrophe occurs in these p53-null cells predominantly as a result of mechanical disruption induced by centrosome overduplication, and not as a consequence of a suicide signal. PMID:21853057

  14. Phosphohistone H3 expression correlates with manual mitotic counts and aids in identification of "hot spots" in fibroepithelial tumors of the breast.

    PubMed

    Ginter, Paula S; Shin, Sandra J; Liu, Yifang; Chen, Zhengming; D'Alfonso, Timothy M

    2016-03-01

    Classification of mammary fibroepithelial tumors (FETs) relies on assessment of mitotic activity, among other histopathologic parameters. Routine hematoxylin and eosin (H&E) mitotic counts can be subjective and time consuming. Difficulty may arise in identifying "true" mitoses for a variety of reasons. Phosphorylation of histone H3 protein (PHH3) is correlated with mitotic chromatin condensation. The utility of PHH3 immunohistochemical staining to identify mitoses has been demonstrated in multiple organ systems. In this study, we examined the utility of PHH3 in assessing mitotic activity in FETs and compared PHH3- with H&E-determined mitotic counts. PHH3-stained mitoses were readily identifiable at 10 magnification and allowed for rapid identification of mitotic "hot spots." Median mitotic counts/10 high-power fields for fibroadenoma, benign phyllodes tumor, borderline phyllodes tumor (BlnPT), and malignant phyllodes tumor (MPT) were 0, 0.5, 4.25, and 9, respectively on H&E, and 0, 0.75, 4.5, and 8, respectively for PHH3. Among all FETs, there was a strong positive correlation between H&E- and PHH3-determined mitotic counts (r=0.91, P<.001). Using PHH3, 2 cases would be reclassified, both from BlnPT to MPT. PHH3-determined counts correlated with H&E-determined counts in FETs. Using PHH3, a small number of cases were reclassified from BlnPT to MPT, for which treatment is similar. Although H&E-determined counts remain the criterion standard for assessing mitotic activity in FETs, PHH3 may be a useful adjunctive tool in some cases and is helpful in identifying mitotic hot spots. PMID:26826415

  15. Mitotic checkpoint control and chromatin remodeling.

    PubMed

    Yao, Yixin; Dai, Wei

    2012-01-01

    In order to maintain chromosomal stability during cell division, eukaryotic cells have evolved a number of surveillance mechanisms termed checkpoints. These checkpoints monitor the completion of essential molecular and cellular processes of one stage before entering another. The spindle checkpoint watches the bi-orientation attachment of spindle microtubules to all condensed chromosomes before initiation of nuclear division during mitosis. Histones are subject to a number of post-translational modifications during the cell cycle, which may in turn modify or facilitate cell cycle progression. Recent studies suggest that mitotic proteins including Bub1 and Sgo1 that are involved in the spindle checkpoint also play a major role in the regulation of histone modifications and chromatin remodeling. This mini-review summarizes emerging information about the new role of spindle checkpoint proteins in chromatin remodeling. PMID:22201785

  16. DEPDC1 is a novel cell cycle related gene that regulates mitotic progression

    PubMed Central

    Mi, Yan; Zhang, Chundong; Bu, Youquan; Zhang, Ying; He, Longxia; Li, Hongxia; Zhu, Huifang; Li, Yi; Lei, Yunlong; Zhu, Jiang

    2015-01-01

    DEPDC1 is a recently identified novel tumor-related gene that is upregulated in several types of cancer and contributes to tumorigenesis. In this study, we have investigated the expression pattern and functional implications of DEPDC1 during cell cycle progression. Expression studies using synchronized cells demonstrated that DEPDC1 is highly expressed in the mitotic phase of the cell cycle. Immunofluorescence assays showed that DEPDC1 is predominantly localized in the nucleus during interphase and is redistributed into the whole cell upon nuclear membrane breakdown in metaphase. Subsequently, siRNA-mediated knockdown of DEPDC1 caused a significant mitotic arrest. Moreover, knockdown of DEPDC1 resulted in remarkable mitotic defects such as abnormal multiple nuclei and multipolar spindle structures accompanied by the upregulation of the A20 gene as well as several cell cycle-related genes such as CCNB1 and CCNB2. Taken together, our current observations strongly suggest that this novel cancerous gene, DEPDC1, plays a pivotal role in the regulation of proper mitotic progression. [BMB Reports 2015; 48(7): 413-418] PMID:25902835

  17. Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint.

    PubMed

    Foss, Kristen M; Robeson, Alexander C; Kornbluth, Sally; Zhang, Liguo

    2016-01-17

    The spindle checkpoint prevents activation of the anaphase-promoting complex (APC/C) until all chromosomes are correctly attached to the mitotic spindle. Early in mitosis, the mitotic checkpoint complex (MCC) inactivates the APC/C by binding the APC/C activating protein CDC20 until the chromosomes are properly aligned and attached to the mitotic spindle, at which point MCC disassembly releases CDC20 to activate the APC/C. Once the APC/C is activated, it targets cyclin B and securin for degradation, and the cell progresses into anaphase. While phosphorylation is known to drive many of the events during the checkpoint, the precise molecular mechanisms regulating spindle checkpoint maintenance and inactivation are still poorly understood. We sought to determine the role of mitotic phosphatases during the spindle checkpoint. To address this question, we treated spindle checkpoint-arrested cells with various phosphatase inhibitors and examined the effect on the MCC and APC/C activation. Using this approach we found that 2 phosphatase inhibitors, calyculin A and okadaic acid (1?M), caused MCC dissociation and APC/C activation leading to cyclin A and B degradation in spindle checkpoint-arrested cells. Although the cells were able to degrade cyclin B, they did not exit mitosis as evidenced by high levels of Cdk1 substrate phosphorylation and chromosome condensation. Our results provide the first evidence that phosphatases are essential for maintenance of the MCC during operation of the spindle checkpoint. PMID:26652909

  18. The flavonoid eupatorin inactivates the mitotic checkpoint leading to polyploidy and apoptosis

    SciTech Connect

    Salmela, Anna-Leena; Turku Graduate School of Biomedical Sciences, Turku; Turku Centre for Biotechnology, P.O. Box 123, University of Turku ; Pouwels, Jeroen; Kukkonen-Macchi, Anu; Waris, Sinikka; Toivonen, Pauliina; Jaakkola, Kimmo; Maeki-Jouppila, Jenni; Turku Centre for Biotechnology, P.O. Box 123, University of Turku; Drug Discovery Graduate School, University of Turku ; Kallio, Lila; Kallio, Marko J.; Turku Centre for Biotechnology, P.O. Box 123, University of Turku; Centre of Excellence for Translational Genome-Scale Biology, P.O. Box 106, Academy of Finland

    2012-03-10

    The spindle assembly checkpoint (SAC) is a conserved mechanism that ensures the fidelity of chromosome distribution in mitosis by preventing anaphase onset until the correct bipolar microtubule-kinetochore attachments are formed. Errors in SAC function may contribute to tumorigenesis by inducing numerical chromosome anomalies (aneuploidy). On the other hand, total disruption of SAC can lead to massive genomic imbalance followed by cell death, a phenomena that has therapeutic potency. We performed a cell-based high-throughput screen with a compound library of 2000 bioactives for novel SAC inhibitors and discovered a plant-derived phenolic compound eupatorin (3 Prime ,5-dihydroxy-4 Prime ,6,7-trimethoxyflavone) as an anti-mitotic flavonoid. The premature override of the microtubule drug-imposed mitotic arrest by eupatorin is dependent on microtubule-kinetochore attachments but not interkinetochore tension. Aurora B kinase activity, which is essential for maintenance of normal SAC signaling, is diminished by eupatorin in cells and in vitro providing a mechanistic explanation for the observed forced mitotic exit. Eupatorin likely has additional targets since eupatorin treatment of pre-mitotic cells causes spindle anomalies triggering a transient M phase delay followed by impaired cytokinesis and polyploidy. Finally, eupatorin potently induces apoptosis in multiple cancer cell lines and suppresses cancer cell proliferation in organotypic 3D cell culture model.

  19. Direct preparation protocol to obtain mitotic chromosomes from canine mammary tumors.

    PubMed

    Morais, C S D; Affonso, P R A M; Bitencourt, J A; Wenceslau, A A

    2015-01-01

    Currently, mammary neoplasms in female canines are a serious problem in veterinary clinics. In addition, the canine species is an excellent disease model for human oncology because of the biological and genetic similarities between the species. Cytogenetics has allowed further study of the characterization of neoplasms in canines. We hypothesized that the use of a direct preparation protocol for mitotic chromosome analysis would provide a simple and low cost protocol for use in all laboratories. The objective of this method is to display in a few hours of dividing cells just like the time of collection since cell division in tissue can be obtained. Ten female canines with the spontaneous occurrence of mammary neoplasia were used to test a pioneering direct preparation protocol to obtain mitotic chromosomes. The excised breast tumor tissue fragments were subjected to the protocol consisting of treatment with colchicine, treatment with hypotonic solution, and fixation. Mitotic chromosomes were absent in cell suspensions of only two samples among the 10 materials analyzed, based on the analysis of five blades for each preparation obtained. So, the cell suspension obtained allowed for the observation of eight tissue samples viable for cytogenetic analysis, five of which had excellent numbers of mitotic chromosomes. However, the technique was unsuccessful in producing high-quality cell suspensions because of inadequate condensation and scattering of chromosomes. While adjustments to methodological procedures are needed, this protocol represents a low cost and simplified method to study the cytogenetics of canine tumors. PMID:26782592

  20. Classification of High Resolution C-Band PolSAR Data on Polarimetric and Texture Features

    NASA Astrophysics Data System (ADS)

    Zhao, Lei; Chen, Erxue; Li, Zengyuan; Feng, Qi; Li, Lan

    2014-11-01

    PolSAR image classification is an important technique in the remote sensing area. For high resolution PolSAR image, polarimetric and texture features are equally important for the high resolution PolSAR image classification. The texture features are mainly extracted through Gray Level Co-occurrence Matrix (GLCM) method, but this method has some deficiencies. First, GLCM method can only work on gray-scale images; Secondly, the number of texture features extracted by GLCM method is generally up dozens, or even hundreds. Too many features may exist larger redundancy and will increase the complexity of classification. Therefore, this paper introduces a new texture feature factor-RK that derived from PolSAR image non-Gaussian statistic model.Using the domestic airborne C-band PolSAR image data, we completed classification combined the polarization and texture characteristics.The results showed that this new texture feature factor-RK can overcome the above drawbacks and can achieve same performance compared with GLCM method.

  1. Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus

    SciTech Connect

    Yang, Feng; Camp, David G.; Gritsenko, Marina A.; Luo, Quanzhou; Kelly, Ryan T.; Clauss, Therese RW; Brinkley, William R.; Smith, Richard D.; Stenoien, David L.

    2007-11-16

    The chromosomal passenger complex (CPC) is a critical regulator of chromosome, cytoskeleton and membrane dynamics during mitosis. Here, we identified phosphopeptides and phosphoprotein complexes recognized by a phosphorylation specific antibody that labels the CPC using liquid chromatography coupled to mass spectrometry. A mitotic phosphorylation motif (PX{G/T/S}{L/M}[pS]P or WGL[pS]P) was identified in 11 proteins including Fzr/Cdh1 and RIC-8, two proteins with potential links to the CPC. Phosphoprotein complexes contained known CPC components INCENP, Aurora-B and TD-60, as well as SMAD2, 14-3-3 proteins, PP2A, and Cdk1, a likely kinase for this motif. Protein sequence analysis identified phosphorylation motifs in additional proteins including SMAD2, Plk3 and INCENP. Mitotic SMAD2 and Plk3 phosphorylation was confirmed using phosphorylation specific antibodies, and in the case of Plk3, phosphorylation correlates with its localization to the mitotic apparatus. A mutagenesis approach was used to show INCENP phosphorylation is required for midbody localization. These results provide evidence for a shared phosphorylation event that regulates localization of critical proteins during mitosis.

  2. A High Precision Feature Based on LBP and Gabor Theory for Face Recognition

    PubMed Central

    Xia, Wei; Yin, Shouyi; Ouyang, Peng

    2013-01-01

    How to describe an image accurately with the most useful information but at the same time the least useless information is a basic problem in the recognition field. In this paper, a novel and high precision feature called BG2D2LRP is proposed, accompanied with a corresponding face recognition system. The feature contains both static texture differences and dynamic contour trends. It is based on Gabor and LBP theory, operated by various kinds of transformations such as block, second derivative, direct orientation, layer and finally fusion in a particular way. Seven well-known face databases such as FRGC, AR, FERET and so on are used to evaluate the veracity and robustness of the proposed feature. A maximum improvement of 29.41% is achieved comparing with other methods. Besides, the ROC curve provides a satisfactory figure. Those experimental results strongly demonstrate the feasibility and superiority of the new feature and method. PMID:23552103

  3. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

    PubMed Central

    Purrington, Kristen S.; Slettedahl, Seth; Bolla, Manjeet K.; Michailidou, Kyriaki; Czene, Kamila; Nevanlinna, Heli; Bojesen, Stig E.; Andrulis, Irene L.; Cox, Angela; Hall, Per; Carpenter, Jane; Yannoukakos, Drakoulis; Haiman, Christopher A.; Fasching, Peter A.; Mannermaa, Arto; Winqvist, Robert; Brenner, Hermann; Lindblom, Annika; Chenevix-Trench, Georgia; Benitez, Javier; Swerdlow, Anthony; Kristensen, Vessela; Guénel, Pascal; Meindl, Alfons; Darabi, Hatef; Eriksson, Mikael; Fagerholm, Rainer; Aittomäki, Kristiina; Blomqvist, Carl; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Wang, Xianshu; Olswold, Curtis; Olson, Janet E.; Mulligan, Anna Marie; Knight, Julia A.; Tchatchou, Sandrine; Reed, Malcolm W.R.; Cross, Simon S.; Liu, Jianjun; Li, Jingmei; Humphreys, Keith; Clarke, Christine; Scott, Rodney; Fostira, Florentia; Fountzilas, George; Konstantopoulou, Irene; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Ekici, Arif B.; Hartmann, Arndt; Beckmann, Matthias W.; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Jukkola-Vuorinen, Arja; Pylkäs, Katri; Kauppila, Saila; Dieffenbach, Aida Karina; Stegmaier, Christa; Arndt, Volker; Margolin, Sara; Balleine, Rosemary; Arias Perez, Jose Ignacio; Pilar Zamora, M.; Menéndez, Primitiva; Ashworth, Alan; Jones, Michael; Orr, Nick; Arveux, Patrick; Kerbrat, Pierre; Truong, Thérèse; Bugert, Peter; Toland, Amanda E.; Ambrosone, Christine B.; Labrèche, France; Goldberg, Mark S.; Dumont, Martine; Ziogas, Argyrios; Lee, Eunjung; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Ficarazzi, Filomena; Barile, Monica; Peterlongo, Paolo; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Brüning, Thomas; Ko, Yon-Dschun; Van Deurzen, Carolien H.M.; Martens, John W.M.; Kriege, Mieke; Figueroa, Jonine D.; Chanock, Stephen J.; Lissowska, Jolanta; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Schneeweiss, Andreas; Tapper, William J.; Gerty, Susan M.; Durcan, Lorraine; Mclean, Catriona; Milne, Roger L.; Baglietto, Laura; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Van'T Veer, Laura J.; Cornelissen, Sten; Försti, Asta; Torres, Diana; Rüdiger, Thomas; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Weltens, Caroline; Floris, Giuseppe; Moisse, Matthieu; Dennis, Joe; Wang, Qin; Dunning, Alison M.; Shah, Mitul; Brown, Judith; Simard, Jacques; Anton-Culver, Hoda; Neuhausen, Susan L.; Hopper, John L.; Bogdanova, Natalia; Dörk, Thilo; Zheng, Wei; Radice, Paolo; Jakubowska, Anna; Lubinski, Jan; Devillee, Peter; Brauch, Hiltrud; Hooning, Maartje; García-Closas, Montserrat; Sawyer, Elinor; Burwinkel, Barbara; Marmee, Frederick; Eccles, Diana M.; Giles, Graham G.; Peto, Julian; Schmidt, Marjanka; Broeks, Annegien; Hamann, Ute; Chang-Claude, Jenny; Lambrechts, Diether; Pharoah, Paul D.P.; Easton, Douglas; Pankratz, V. Shane; Slager, Susan; Vachon, Celine M.; Couch, Fergus J.

    2014-01-01

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16–1.33, P = 4.2 × 10−10) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04–1.11, P = 8.7 × 10−6) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07–1.23, P = 7.9 × 10−5) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10−3). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer. PMID:24927736

  4. Study on atomization features of a plain injector in high speed transverse air stream

    NASA Astrophysics Data System (ADS)

    Wan, Jian; Gu, Shanjian; Yang, Maolin; Xiao, Weihui

    1990-04-01

    The atomization features of a plain injector in high-speed transverse air stream were investigated by Malvern. In this investigation, air velocity ranged from 50-150m/s, pressure drop of fuel injector, (1.1 - 4.2) x 10 to the 6th Pa, diameter of orifice, 0.5 - 0.9 mm, axial distance between the injector and the survey plane, 50 - 250 mm. Aviation kerosene was used in all experiments. It was found that the atomization features in high pressure drop of fuel injector were greatly differed from the low pressure drop of fuel injector.

  5. Fabrication of a high-resolution roll for gravure printing of 2μm features

    NASA Astrophysics Data System (ADS)

    Grau, Gerd; Kitsomboonloha, Rungrot; Subramanian, Vivek

    2015-08-01

    High-resolution features are key to achieve high performance printed electronics devices such as transistors. Gravure printing is very promising to achieve high resolution in combination with high printing speeds on the order of 1m/s. High-speed gravure has recently been shown to print high resolution features down to linewidths and spacing of 2μm. Whilst this was a tremendous improvement over previous reports, these results had been obtained using silicon printing plates. These silicon printing plates are fabricated using microfabrication techniques which offer several advantages over traditional metal gravure cylinders where the features are defined by techniques such as stylus engraving, laser engraving or etching. This offers much greater precision and design freedom in terms of feature size, surface roughness, cell placement and cell shape. However, rigid silicon printing plates cannot be used in a roll-to-roll printing process that would truly enable low-cost printed electronics. Here we demonstrate for the first time a gravure printing roll that combines the precision of silicon printing plates with the form factor of a metal cylinder. The fabrication process starts with a silicon master whose pattern is replicated by polymer molding. The actual metal printing plate is then built up on the polymer negative of the pattern by a combination of electroless and electroplating. After separation of the polymer and the metal, the metal printing plate can be mounted on a magnetic roll for printing. Printing of highly scaled 2μm features is demonstrated. Different metal surfaces were explored to optimize printing performance and wear during printing.

  6. Arsenic Trioxide Suppresses Paclitaxel-Induced Mitotic Arrest

    PubMed Central

    Duan, Qing; Komissarova, Elena; Dai, Wei

    2014-01-01

    To human health, arsenic exhibits the property of a double-edged sword. Arsenic compounds such as As2O3 is effective for the treatment of relapsed/refractory acute promyelocytic leukemia, whereas chronic exposure to environmental arsenic is associated with the development of a variety of common cancers. Because As2O3 is capable of inhibiting tubulin polymerization and inducing mitotic arrest, we examined whether there existed any functional interaction between As2O3 and paclitaxel, a well-known microtubule poison. Flow cytometry and fluorescence microscopy revealed that although As2O3 alone caused a moderate level of mitotic arrest, it greatly attenuated paclitaxel-induced mitotic arrest in cells with p53 deficiency. Western blot analysis showed that As2O3 significantly blocked phosphorylation of BubR1, Cdc20, and Cdc27 in cells treated with paclitaxel, suggesting that arsenic compromised the activation of the spindle checkpoint. Our further studies revealed that the attenuation of paclitaxel-induced mitotic arrest by As2O3 resulted primarily from sluggish cell cycle progression at S phase but not enhanced mitotic exit. The clinical efficacy of taxol is associated with its ability to induce mitotic arrest and subsequent mitotic catastrophe. Our observations that As2O3 has a negative impact on the cell cycle checkpoint activation by taxol should have significant clinical implications. PMID:19397590

  7. Cell Death During Crisis Is Mediated by Mitotic Telomere Deprotection

    PubMed Central

    Hayashi, Makoto T.; Cesare, Anthony J.; Rivera, Teresa; Karlseder, Jan

    2015-01-01

    Tumour formation is blocked by two barriers, replicative senescence and crisis1. Senescence is triggered by short telomeres and is bypassed by disruption of tumour suppressive pathways. After senescence bypass, cells undergo crisis, during which almost all of the cells in the population die. Cells that escape crisis harbor unstable genomes and other parameters of transformation. The mechanism of cell death during crisis remained elusive. We show that cells in crisis undergo spontaneous mitotic arrest, resulting in death during mitosis or in the following cell cycle. The phenotype was induced by loss of p53 function, and suppressed by telomerase overexpression. Telomere fusions triggered mitotic arrest in p53-compromised non-crisis cells, indicating such fusions as the underlying cause. Exacerbation of mitotic telomere deprotection by partial TRF2 knockdown2 increased the ratio of cells that died during mitotic arrest and sensitized cancer cells to mitotic poisons. We propose a crisis pathway wherein chromosome fusions induce mitotic arrest, resulting in mitotic telomere deprotection and cell death, thereby eliminating precancerous cells from the population. PMID:26108857

  8. Application of high-dimensional feature selection: evaluation for genomic prediction in man

    PubMed Central

    Bermingham, M. L.; Pong-Wong, R.; Spiliopoulou, A.; Hayward, C.; Rudan, I.; Campbell, H.; Wright, A. F.; Wilson, J. F.; Agakov, F.; Navarro, P.; Haley, C. S.

    2015-01-01

    In this study, we investigated the effect of five feature selection approaches on the performance of a mixed model (G-BLUP) and a Bayesian (Bayes C) prediction method. We predicted height, high density lipoprotein cholesterol (HDL) and body mass index (BMI) within 2,186 Croatian and into 810 UK individuals using genome-wide SNP data. Using all SNP information Bayes C and G-BLUP had similar predictive performance across all traits within the Croatian data, and for the highly polygenic traits height and BMI when predicting into the UK data. Bayes C outperformed G-BLUP in the prediction of HDL, which is influenced by loci of moderate size, in the UK data. Supervised feature selection of a SNP subset in the G-BLUP framework provided a flexible, generalisable and computationally efficient alternative to Bayes C; but careful evaluation of predictive performance is required when supervised feature selection has been used. PMID:25988841

  9. Application of high-dimensional feature selection: evaluation for genomic prediction in man.

    PubMed

    Bermingham, M L; Pong-Wong, R; Spiliopoulou, A; Hayward, C; Rudan, I; Campbell, H; Wright, A F; Wilson, J F; Agakov, F; Navarro, P; Haley, C S

    2015-01-01

    In this study, we investigated the effect of five feature selection approaches on the performance of a mixed model (G-BLUP) and a Bayesian (Bayes C) prediction method. We predicted height, high density lipoprotein cholesterol (HDL) and body mass index (BMI) within 2,186 Croatian and into 810 UK individuals using genome-wide SNP data. Using all SNP information Bayes C and G-BLUP had similar predictive performance across all traits within the Croatian data, and for the highly polygenic traits height and BMI when predicting into the UK data. Bayes C outperformed G-BLUP in the prediction of HDL, which is influenced by loci of moderate size, in the UK data. Supervised feature selection of a SNP subset in the G-BLUP framework provided a flexible, generalisable and computationally efficient alternative to Bayes C; but careful evaluation of predictive performance is required when supervised feature selection has been used. PMID:25988841

  10. Multi-task hidden Markov modeling of spectrogram feature from radar high-resolution range profiles

    NASA Astrophysics Data System (ADS)

    Pan, Mian; Du, Lan; Wang, Penghui; Liu, Hongwei; Bao, Zheng

    2012-12-01

    In radar high-resolution range profile (HRRP)-based statistical target recognition, one of the most challenging task is the feature extraction. This article utilizes spectrogram feature of HRRP data for improving the recognition performance, of which the spectrogram is a two-dimensional feature providing the variation of frequency domain feature with time domain feature. And then, a new radar HRRP target recognition method is presented via a truncated stick-breaking hidden Markov model (TSB-HMM). Moreover, multi-task learning (MTL) is employed, from which a full posterior distribution on the numbers of states associated with the targets can be inferred and the target-dependent states information are shared among multiple target-aspect frames of each target. The framework of TSB-HMM allows efficient variational Bayesian inference, of interest for large-scale problem. Experimental results for measured data show that the spectrogram feature has significant advantages over the time domain sample in both the recognition and rejection performance, and MTL provides a better recognition performance.

  11. High-accuracy real-time pedestrian detection system using 2D and 3D features

    NASA Astrophysics Data System (ADS)

    Chambers, David R.; Flannigan, Clay; Wheeler, Benjamin

    2012-06-01

    We present a real time stereo-vision pedestrian detector implementation with a very high accuracy, the 2D component of which attains 99% recall with less than 10-6 false positives per window on the INRIA persons dataset. We utilize a sequence of classifiers which use different features, beginning with Haar-like features and a Haar-like feature implementation adapted to disparity images, and performing a final verification with Histogram-of-Oriented Gradient (HOG) features. We present a 2D Haar-like feature implementation that utilizes 2x2 kernel filters at multiple scales rather than integral images, and combines a quickly trained preliminary adaBoost classifier with a more accurate SVM classifier. We also show how these Haar-like features may be computed from a partially incomplete stereo disparity image in order to make use of 3-dimensional data. Finally, we discuss how these features, along with the HOG features, are computed rapidly and how the classifiers are combined in such a way as to enable real-time implementation with higher detection rates and lower false positive rates than typical systems. Our overall detector is a practical combination of speed and detection performance, operating on 544x409 image (10,425 windows) at a frame rate of 10-20fps, depending on scene complexity. The detector's overall false positive rate is less than 10-6, corresponding to about one false positive every 10-60s when testing on our non-training data. Additionally, the detector has shown usefulness for detecting other object types, and has been implemented for traffic cones, telephone poles, and vehicles.

  12. Access, Participation, and Supports: The Defining Features of High-Quality Inclusion

    ERIC Educational Resources Information Center

    Buysse, Virginia

    2011-01-01

    This article describes current knowledge about early childhood inclusion, summarizing research and the DEC/NAEYC joint position statement on inclusion. The article also describes effective or promising educational practices that promote access, participation, and supports--the defining features of high-quality inclusion. Future efforts to improve…

  13. Assessing Motor Skills as a Differentiating Feature between High Functioning Autism and Asperger's Disorder

    ERIC Educational Resources Information Center

    Cid, Maria R.

    2011-01-01

    The purpose of this research was to investigate if motor skills could be used as a differentiating feature between Asperger's Disorder (AD) and High Functioning (HFA) in children under the age of 9 years, 0 months, in order to provide additional information regarding the usefulness and validity of distinguishing these two disorders. There is

  14. Access, Participation, and Supports: The Defining Features of High-Quality Inclusion

    ERIC Educational Resources Information Center

    Buysse, Virginia

    2011-01-01

    This article describes current knowledge about early childhood inclusion, summarizing research and the DEC/NAEYC joint position statement on inclusion. The article also describes effective or promising educational practices that promote access, participation, and supports--the defining features of high-quality inclusion. Future efforts to improve

  15. The centrosome and mitotic spindle apparatus in cancer and senescence.

    PubMed

    Schmidt, Stephen; Essmann, Frank; Cirstea, Ion C; Kuck, Fabian; Thakur, Harish C; Singh, Madhurendra; Kletke, Anja; Jänicke, Reiner U; Wiek, Constanze; Hanenberg, Helmut; Ahmadian, M Reza; Schulze-Osthoff, Klaus; Nürnberg, Bernd; Piekorz, Roland P

    2010-11-15

    Altered cell division is associated with overproliferation and tumorigenesis, however, mitotic aberrations can also trigger antiproliferative responses leading to postmitotic cell cycle exit. Here, we focus on the role of the centrosome and in particular of centrosomal TACC (transforming acidic coiled coil) proteins in tumorigenesis and cellular senescence. We have complied recent evidence that inhibition or depletion of various mitotic proteins which take over key in centrosome and kinetochore integrity and mitotic checkpoint function in sufficient to activate a p53-p21(WAF) driven premature senescence phenotype. These findings have direct implications for proliferative tissue homeostasis as well as for cellular and organismal aging. PMID:21088502

  16. Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential.

    PubMed

    Akaike, Keisuke; Kurisaki-Arakawa, Aiko; Hara, Kieko; Suehara, Yoshiyuki; Takagi, Tatsuya; Mitani, Keiko; Kaneko, Kazuo; Yao, Takashi; Saito, Tsuyoshi

    2015-03-01

    The impact of NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion on the biological behavior and the mechanism of acquisition of malignant phenotype in solitary fibrous tumor (SFT) is not well understood. We examined variations of the NAB2-STAT6 fusion gene in 40 cases of SFT using formalin-fixed, paraffin-embedded tissues and secondary genetic alterations of tumor protein p53 (TP53),, platelet-derived growth factor receptor, β polypeptide (PDGFRB), and telomerase reverse transcriptase (TERT) promoters. These gene variations were compared with the clinicopathological features. The 2-year and 5-year disease-free survival rates (DFSRs) were 91% and 83%, respectively. All 40 samples demonstrated nuclear staining for STAT6, including CD34-negative cases. Moreover, p53-positive staining was associated with a lower DFSR and was significantly associated with higher Ki-67 label index, higher mitotic rate (mitosis, >4/high-power field), and the presence of nuclear atypia/pleomorphism. NAB2-STAT6 fusions were detected in all of the cases; the NAB2 exon 4-STAT6 exon 2, the most common genotype, appeared in 18 cases, which was associated with thoracic tumor location and the less aggressive phenotype. In contrast, tumors with NAB2 exon 6-STAT6 exon 16/18 demonstrated an aggressive phenotype. Mutations in TP53 and PDGFRB were detected in 2 and 3 cases respectively, and these occurred in a mutually exclusive fashion. TERT promoter hot spot mutations were observed in 5 cases, which were associated with shorter DFSR. Two dedifferentiated SFT cases harbored both TP53 and TERT promoter mutations. TP53 mutations, which result in its overexpression, in combination with TERT promoter mutations seem to play an important role in the dedifferentiation process. PMID:25582503

  17. Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma.

    PubMed

    Duregon, Eleonora; Molinaro, Luca; Volante, Marco; Ventura, Laura; Righi, Luisella; Bolla, Stefania; Terzolo, Massimo; Sapino, Anna; Papotti, Mauro G

    2014-09-01

    Mitotic count on hematoxylin and eosin slides is a fundamental morphological criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring system employed. Moreover, it is the unique term strongly associated with patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was already proven to facilitate mitotic count in melanoma and other tumors. Therefore, a study was designed to assess the diagnostic and prognostic role of phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and computerized count to standard manual hematoxylin- and eosin-based method and Ki-67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were highly correlated (r=0.9077, P<0.0001), better than computer-assisted phospho-histone H3 evaluations, and had an excellent inter-observer reproducibility at Bland-Altman analysis. Three of 15 cases having <5 mitotic figures per 50 high-power fields by standard count on hematoxylin and eosin gained the mitotic figure point of Weiss Score after a manual count on phospho-histone H3 slides. Traditional mitotic count confirmed to be a strong predictor of overall survival (P=0.0043), better than phospho-histone H3-based evaluation (P=0.051), but not as strong as the Ki-67 index (P<0.0001). The latter further segregated adrenocortical carcinomas into three prognostic groups, stratifying cases by low (<20%), intermediate (20-50%), and high (>50%) Ki-67 values. We conclude that (a) phospho-histone H3 staining is a useful diagnostic complementary tool to standard hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation (including atypical mitotic figures) even in adrenocortical carcinomas with a low mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the best prognostic indicator of overall survival, being superior to the mitotic index, irrespective of the method (standard on hematoxylin and eosin or phospho-histone H3-based) used to count mitotic figures. PMID:24434900

  18. A unique assemblage of epibenthic sessile suspension feeders with archaic features in the high-Antarctic

    NASA Astrophysics Data System (ADS)

    Gili, Josep-Maria; Arntz, Wolf E.; Palanques, Albert; Orejas, Covadonga; Clarke, Andrew; Dayton, Paul K.; Isla, Enrique; Teixid, Nuria; Rossi, Sergio; Lpez-Gonzlez, Pablo J.

    2006-04-01

    We suggest that the epibenthic communities of passive suspension feeders that dominate some high-Antarctic seafloors present unique archaic features that are the result of long isolation, together with the effects of environmental features including reduced terrestrial runoff and favourable feeding conditions. These features probably originated during the Late Cretaceous, when the high-Antarctic environment started to become different from the surrounding oceans. Modern Antarctic communities are thus composed of a mixture of Palaeozoic elements, taxa that migrated from the deep ocean during interglacial periods, and a component of fauna that evolved from common Gondwana Cretaceous ancestors. We explore this hypothesis by revisiting the palaeoecological history of Antarctic marine benthic communities and exploring the abiotic and biotic factors involved in their evolution, including changes in oceanic circulation and production, plankton communities, the development of glaciation, restricted sedimentation, isolation, life histories, and the lack of large predators. The conditions favouring the retention of apparently archaic features in the Antarctic marine fauna remain to be fully elucidated, but high-Antarctic communities are clearly unique and deserve special conservation.

  19. High-resolution FTIR imaging of colon tissues for elucidation of individual cellular and histopathological features.

    PubMed

    Nallala, Jayakrupakar; Lloyd, Gavin Rhys; Shepherd, Neil; Stone, Nick

    2016-01-01

    Novel technologies that could complement current histopathology based cancer diagnostic methods are under examination. In this endeavour mid-infrared spectroscopic imaging is a promising candidate that can provide valuable bio-molecular information from unstained cells and tissues in a rapid and a non-destructive manner. With this imaging technique, the biochemical information obtained from smaller areas of the tissues can be of clinical significance and hence the measured pixel size. Until recently it was difficult to obtain spectral data from pixels below around 5 microns square. High NA objectives have been utilised to reduce the ideal diffraction limit, enabling for the first time elucidation of subcellular features. In this context, the ability of high-resolution imaging, obtained using novel high-magnification optics retro-fitted onto a bench top FTIR imaging system, to characterise histopathological features in colonic tissues has been tested. Formalin fixed paraffin embedded colon tissues from three different pathologies were imaged directly using the conventional and the high-magnification imaging set-ups. To circumvent chemical de-paraffinization protocols, an extended multiplicative signal correction (EMSC) based electronic de-paraffinization was carried out on all the infrared images. Multivariate analysis of the high-magnification infrared imaging data showed a detailed information of the histological features of the colon tissue in comparison to conventional imaging. Furthermore, high-magnification imaging has enabled a label-free characterization of the mucin rich goblet cell features in an unprecedented manner. The current study demonstrates the applicability of high-magnification FTIR imaging to characterise complex tissues on a smaller scale that could be of clinical significance. PMID:26549223

  20. Extracting features buried within high density atom probe point cloud data through simplicial homology.

    PubMed

    Srinivasan, Srikant; Kaluskar, Kaustubh; Broderick, Scott; Rajan, Krishna

    2015-12-01

    Feature extraction from Atom Probe Tomography (APT) data is usually performed by repeatedly delineating iso-concentration surfaces of a chemical component of the sample material at different values of concentration threshold, until the user visually determines a satisfactory result in line with prior knowledge. However, this approach allows for important features, buried within the sample, to be visually obscured by the high density and volume (~10(7) atoms) of APT data. This work provides a data driven methodology to objectively determine the appropriate concentration threshold for classifying different phases, such as precipitates, by mapping the topology of the APT data set using a concept from algebraic topology termed persistent simplicial homology. A case study of Sc precipitates in an Al-Mg-Sc alloy is presented demonstrating the power of this technique to capture features, such as precise demarcation of Sc clusters and Al segregation at the cluster boundaries, not easily available by routine visual adjustment. PMID:25959554

  1. A comprehensive analysis of earthquake damage patterns using high dimensional model representation feature selection

    NASA Astrophysics Data System (ADS)

    Ta?kin Kaya, Gl?en

    2013-10-01

    Recently, earthquake damage assessment using satellite images has been a very popular ongoing research direction. Especially with the availability of very high resolution (VHR) satellite images, a quite detailed damage map based on building scale has been produced, and various studies have also been conducted in the literature. As the spatial resolution of satellite images increases, distinguishability of damage patterns becomes more cruel especially in case of using only the spectral information during classification. In order to overcome this difficulty, textural information needs to be involved to the classification to improve the visual quality and reliability of damage map. There are many kinds of textural information which can be derived from VHR satellite images depending on the algorithm used. However, extraction of textural information and evaluation of them have been generally a time consuming process especially for the large areas affected from the earthquake due to the size of VHR image. Therefore, in order to provide a quick damage map, the most useful features describing damage patterns needs to be known in advance as well as the redundant features. In this study, a very high resolution satellite image after Iran, Bam earthquake was used to identify the earthquake damage. Not only the spectral information, textural information was also used during the classification. For textural information, second order Haralick features were extracted from the panchromatic image for the area of interest using gray level co-occurrence matrix with different size of windows and directions. In addition to using spatial features in classification, the most useful features representing the damage characteristic were selected with a novel feature selection method based on high dimensional model representation (HDMR) giving sensitivity of each feature during classification. The method called HDMR was recently proposed as an efficient tool to capture the input-output relationships in high-dimensional systems for many problems in science and engineering. The HDMR method is developed to improve the efficiency of the deducing high dimensional behaviors. The method is formed by a particular organization of low dimensional component functions, in which each function is the contribution of one or more input variables to the output variables.

  2. Uranus' Persistent Patterns and Features from High-SNR Imaging in 2012-2014

    NASA Astrophysics Data System (ADS)

    Fry, Patrick M.; Sromovsky, Lawrence A.; de Pater, Imke; Hammel, Heidi B.; Marcus, Phillip

    2015-11-01

    Since 2012, Uranus has been the subject of an observing campaign utilizing high signal-to-noise imaging techniques at Keck Observatory (Fry et al. 2012, Astron. J. 143, 150-161). High quality observing conditions on four observing runs of consecutive nights allowed longitudinally-complete coverage of the atmosphere over a period of two years (Sromovsky et al. 2015, Icarus 258, 192-223). Global mosaic maps made from images acquired on successive nights in August 2012, November 2012, August 2013, and August 2014, show persistent patterns, and six easily distinguished long-lived cloud features, which we were able to track for long periods that ranged from 5 months to over two years. Two at similar latitudes are associated with dark spots, and move with the atmospheric zonal flow close to the location of their associated dark spot instead of following the flow at the latitude of the bright features. These features retained their morphologies and drift rates in spite of several close interactions. A second pair of features at similar latitudes also survived several close approaches. Several of the long-lived features also exhibited equatorward drifts and latitudinal oscillations. Also persistent are a remarkable near-equatorial wave feature and global zonal band structure. We will present imagery, maps, and analyses of these phenomena.PMF and LAS acknowledge support from NASA Planetary Astronomy Program; PMF and LAS acknowledge funding and technical support from W. M. Keck Observatory. We thank those of Hawaiian ancestry on whose sacred mountain we are privileged to be guests. Without their generous hospitality none of our groundbased observations would have been possible.

  3. Deep subwavelength mask assist features and mask errors printability in high NA lithography

    NASA Astrophysics Data System (ADS)

    Cheng, Wen-Hao; Lee, Mindy; Tolani, Vikram; Nakahma, Mark; Gleason, Bob

    2006-10-01

    As silicon processes scale toward the 45 nm node using conventional 0.25 magnification, widths of sub-resolution assist feature (SRAF) and printable defects on photomasks drop far below the ArF laser wavelength. Adoption of polarized illumination and higher numerical aperture (NA) could invalidate the scaling relations we used in the past to determine which small mask features or errors will print on wafers. Polarization interaction with small mask features may also plays a role in mask inspection. As mask features shrink below the wavelength, differences between the optical systems used for inspection and printing become more significant, and may affect the rules for disposition of inspection results. The data presented here combines experimental results from high NA imaging of sub-wavelength SRAF and defects, with rigorous calculation of their images based on vector diffraction. The printability of these deep subwavelength mask feature determines the requirements of optical model's rigorousness for SRAF design rule and also mask defect inspection and repair capabilities.

  4. Cell Size Modulates Oscillation, Positioning and Length of Mitotic Spindles

    PubMed Central

    Jiang, Hongyuan

    2015-01-01

    Mitotic spindle is the main subcellular structure that accomplishes the chromosome segregation between daughter cells during cell division. However, how mitotic spindles sense and control their size, position and movement inside the cell still remains unclear. In this paper, we focus on the size effects of mitotic spindles, i.e., how cell size controls various interesting phenomena in the metaphase, such as oscillation, positioning and size limit of mitotic spindles. We systematically studied the frequency doubling phenomenon during chromosome oscillation and found that cell size can regulate the period and amplitude of chromosome oscillation. We found that the relaxation time of the positioning process increases exponentially with cell size. We also showed that the stabler microtubule-kinetochore attachments alone can directly lead to an upper limit of spindle size. Our work not only explains the existing experimental observations, but also provides some interesting predictions that can be verified or rejected by further experiments. PMID:26015263

  5. Human LATS1 is a mitotic exit network kinase.

    PubMed

    Bothos, John; Tuttle, Robyn L; Ottey, Michelle; Luca, Francis C; Halazonetis, Thanos D

    2005-08-01

    The kinase LATS/WARTS is a tumor suppressor protein conserved in evolution, but its function at the molecular level is not well understood. We report here that human LATS1 interacts with MOB1A, a protein whose homologue in budding yeast associates with kinases involved in mitotic exit. This suggested that LATS1 may be a component of the previously uncharacterized mitotic exit network in higher eukaryotes. Indeed, moderate overexpression of human LATS1 in cells exposed to microtubule poisons facilitated mitotic exit, and this activity required MOB1A. Reciprocally, small interfering RNA-mediated suppression of LATS1 or MOB1A prolonged telophase, but had no effect on the length of the earlier phases of mitosis. A role of LATS1 in mitotic exit may explain its previously described abilities to induce G2 arrest and promote cytokinesis. PMID:16061636

  6. The bipolar assembly domain of the mitotic motor kinesin-5

    PubMed Central

    Acar, Seyda; Carlson, David B.; Budamagunta, Madhu S.; Yarov-Yarovoy, Vladimir; Correia, John J.; Niñonuevo, Milady R.; Jia, Weitao; Tao, Li; Leary, Julie A.; Voss, John C.; Evans, James E.; Scholey, Jonathan M.

    2013-01-01

    An outstanding unresolved question is how does the mitotic spindle utilize microtubules and mitotic motors to coordinate accurate chromosome segregation during mitosis? This process depends upon the mitotic motor, kinesin-5, whose unique bipolar architecture, with pairs of motor domains lying at opposite ends of a central rod, allows it to crosslink microtubules within the mitotic spindle and to coordinate their relative sliding during spindle assembly, maintenance and elongation. The structural basis of kinesin-5’s bipolarity is, however, unknown, as protein asymmetry has so far precluded its crystallization. Here we use electron microscopy of single molecules of kinesin-5 and its subfragments, combined with hydrodynamic analysis plus mass spectrometry, circular dichroism and site-directed spin label electron paramagnetic resonance spectroscopy, to show how a staggered antiparallel coiled-coil ‘BASS’ (bipolar assembly) domain directs the assembly of four kinesin-5 polypeptides into bipolar minifilaments. PMID:23299893

  7. Sister chromatid exchanges and mitotic crossing-over

    SciTech Connect

    1993-12-31

    Chapter 12, discusses sister chromatid exchanges (SCE) and mitotic crossing-over. The detection, occurrence and use of SCE in mutagenesis research is covered, as is segregation, chiasmata and gene amplification. 28 refs., 5 figs.

  8. A PLANETARY LENSING FEATURE IN CAUSTIC-CROSSING HIGH-MAGNIFICATION MICROLENSING EVENTS

    SciTech Connect

    Chung, Sun-Ju; Hwang, Kyu-Ha; Ryu, Yoon-Hyun; Lee, Chung-Uk E-mail: kyuha@kasi.re.kr E-mail: leecu@kasi.re.kr

    2012-05-20

    Current microlensing follow-up observations focus on high-magnification events because of the high efficiency of planet detection. However, central perturbations of high-magnification events caused by a planet can also be produced by a very close or a very wide binary companion, and the two kinds of central perturbations are not generally distinguished without time consuming detailed modeling (a planet-binary degeneracy). Hence, it is important to resolve the planet-binary degeneracy that occurs in high-magnification events. In this paper, we investigate caustic-crossing high-magnification events caused by a planet and a wide binary companion. From this investigation, we find that because of the different magnification excess patterns inside the central caustics induced by the planet and the binary companion, the light curves of the caustic-crossing planetary-lensing events exhibit a feature that is discriminated from those of the caustic-crossing binary-lensing events, and the feature can be used to immediately distinguish between the planetary and binary companions. The planetary-lensing feature appears in the interpeak region between the two peaks of the caustic-crossings. The structure of the interpeak region for the planetary-lensing events is smooth and convex or boxy, whereas the structure for the binary-lensing events is smooth and concave. We also investigate the effect of a finite background source star on the planetary-lensing feature in the caustic-crossing high-magnification events. From this, we find that the convex-shaped interpeak structure appears in a certain range that changes with the mass ratio of the planet to the planet-hosting star.

  9. Physical limits on kinesin-5-mediated chromosome congression in the smallest mitotic spindles.

    PubMed

    McCoy, Kelsey M; Tubman, Emily S; Claas, Allison; Tank, Damien; Clancy, Shelly Applen; O'Toole, Eileen T; Berman, Judith; Odde, David J

    2015-11-01

    A characteristic feature of mitotic spindles is the congression of chromosomes near the spindle equator, a process mediated by dynamic kinetochore microtubules. A major challenge is to understand how precise, submicrometer-scale control of kinetochore micro-tubule dynamics is achieved in the smallest mitotic spindles, where the noisiness of microtubule assembly/disassembly will potentially act to overwhelm the spatial information that controls microtubule plus end-tip positioning to mediate congression. To better understand this fundamental limit, we conducted an integrated live fluorescence, electron microscopy, and modeling analysis of the polymorphic fungal pathogen Candida albicans, which contains one of the smallest known mitotic spindles (<1 ?m). Previously, ScCin8p (kinesin-5 in Saccharomyces cerevisiae) was shown to mediate chromosome congression by promoting catastrophe of long kinetochore microtubules (kMTs). Using C. albicans yeast and hyphal kinesin-5 (Kip1p) heterozygotes (KIP1/kip1?), we found that mutant spindles have longer kMTs than wild-type spindles, consistent with a less-organized spindle. By contrast, kinesin-8 heterozygous mutant (KIP3/kip3?) spindles exhibited the same spindle organization as wild type. Of interest, spindle organization in the yeast and hyphal states was indistinguishable, even though yeast and hyphal cell lengths differ by two- to fivefold, demonstrating that spindle length regulation and chromosome congression are intrinsic to the spindle and largely independent of cell size. Together these results are consistent with a kinesin-5-mediated, length-dependent depolymerase activity that organizes chromosomes at the spindle equator in C. albicans to overcome fundamental noisiness in microtubule self-assembly. More generally, we define a dimensionless number that sets a fundamental physical limit for maintaining congression in small spindles in the face of assembly noise and find that C. albicans operates very close to this limit, which may explain why it has the smallest known mitotic spindle that still manifests the classic congression architecture. PMID:26354423

  10. Physical limits on kinesin-5mediated chromosome congression in the smallest mitotic spindles

    PubMed Central

    McCoy, Kelsey M.; Tubman, Emily S.; Claas, Allison; Tank, Damien; Clancy, Shelly Applen; OToole, Eileen T.; Berman, Judith; Odde, David J.

    2015-01-01

    A characteristic feature of mitotic spindles is the congression of chromosomes near the spindle equator, a process mediated by dynamic kinetochore microtubules. A major challenge is to understand how precise, submicrometer-scale control of kinetochore microtubule dynamics is achieved in the smallest mitotic spindles, where the noisiness of microtubule assembly/disassembly will potentially act to overwhelm the spatial information that controls microtubule plus endtip positioning to mediate congression. To better understand this fundamental limit, we conducted an integrated live fluorescence, electron microscopy, and modeling analysis of the polymorphic fungal pathogen Candida albicans, which contains one of the smallest known mitotic spindles (<1 ?m). Previously, ScCin8p (kinesin-5 in Saccharomyces cerevisiae) was shown to mediate chromosome congression by promoting catastrophe of long kinetochore microtubules (kMTs). Using C. albicans yeast and hyphal kinesin-5 (Kip1p) heterozygotes (KIP1/kip1?), we found that mutant spindles have longer kMTs than wild-type spindles, consistent with a less-organized spindle. By contrast, kinesin-8 heterozygous mutant (KIP3/kip3?) spindles exhibited the same spindle organization as wild type. Of interest, spindle organization in the yeast and hyphal states was indistinguishable, even though yeast and hyphal cell lengths differ by two- to fivefold, demonstrating that spindle length regulation and chromosome congression are intrinsic to the spindle and largely independent of cell size. Together these results are consistent with a kinesin-5mediated, length-dependent depolymerase activity that organizes chromosomes at the spindle equator in C. albicans to overcome fundamental noisiness in microtubule self-assembly. More generally, we define a dimensionless number that sets a fundamental physical limit for maintaining congression in small spindles in the face of assembly noise and find that C. albicans operates very close to this limit, which may explain why it has the smallest known mitotic spindle that still manifests the classic congression architecture. PMID:26354423

  11. Mitotic Diversity in Homeostatic Human Interfollicular Epidermis.

    PubMed

    Nske, Katharina; Stark, Hans-Jrgen; Nevaril, Leonard; Berning, Manuel; Langbein, Lutz; Goyal, Ashish; Diederichs, Sven; Boukamp, Petra

    2016-01-01

    Despite decades of skin research, regulation of proliferation and homeostasis in human epidermis is still insufficiently understood. To address the role of mitoses in tissue regulation, we utilized human long-term skin equivalents and systematically assessed mitoses during early epidermal development and long-term epidermal regeneration. We now demonstrate four different orientations: (1) horizontal, i.e., parallel to the basement membrane (BM) and suggestive of symmetric divisions; (2) oblique with an angle of 45-70; or (3) perpendicular, suggestive of asymmetric division. In addition, we demonstrate a fourth substantial fraction of suprabasal mitoses, many of which are committed to differentiation (Keratin K10-positive). As verified also for normal human skin, this spatial mitotic organization is part of the regulatory program of human epidermal tissue homeostasis. As a potential marker for asymmetric division, we investigated for Numb and found that it was evenly spread in almost all undifferentiated keratinocytes, but indeed asymmetrically distributed in some mitoses and particularly frequent under differentiation-repressing low-calcium conditions. Numb deletion (stable knockdown by CRISPR/Cas9), however, did not affect proliferation, neither in a three-day follow up study by life cell imaging nor during a 14-day culture period, suggesting that Numb is not essential for the general control of keratinocyte division. PMID:26828486

  12. Mitotic Diversity in Homeostatic Human Interfollicular Epidermis

    PubMed Central

    Nöske, Katharina; Stark, Hans-Jürgen; Nevaril, Leonard; Berning, Manuel; Langbein, Lutz; Goyal, Ashish; Diederichs, Sven; Boukamp, Petra

    2016-01-01

    Despite decades of skin research, regulation of proliferation and homeostasis in human epidermis is still insufficiently understood. To address the role of mitoses in tissue regulation, we utilized human long-term skin equivalents and systematically assessed mitoses during early epidermal development and long-term epidermal regeneration. We now demonstrate four different orientations: (1) horizontal, i.e., parallel to the basement membrane (BM) and suggestive of symmetric divisions; (2) oblique with an angle of 45°–70°; or (3) perpendicular, suggestive of asymmetric division. In addition, we demonstrate a fourth substantial fraction of suprabasal mitoses, many of which are committed to differentiation (Keratin K10-positive). As verified also for normal human skin, this spatial mitotic organization is part of the regulatory program of human epidermal tissue homeostasis. As a potential marker for asymmetric division, we investigated for Numb and found that it was evenly spread in almost all undifferentiated keratinocytes, but indeed asymmetrically distributed in some mitoses and particularly frequent under differentiation-repressing low-calcium conditions. Numb deletion (stable knockdown by CRISPR/Cas9), however, did not affect proliferation, neither in a three-day follow up study by life cell imaging nor during a 14-day culture period, suggesting that Numb is not essential for the general control of keratinocyte division. PMID:26828486

  13. Airborne LIDAR and high resolution satellite data for rapid 3D feature extraction

    NASA Astrophysics Data System (ADS)

    Jawak, S. D.; Panditrao, S. N.; Luis, A. J.

    2014-11-01

    This work uses the canopy height model (CHM) based workflow for individual tree crown delineation and 3D feature extraction approach (Overwatch Geospatial's proprietary algorithm) for building feature delineation from high-density light detection and ranging (LiDAR) point cloud data in an urban environment and evaluates its accuracy by using very high-resolution panchromatic (PAN) (spatial) and 8-band (multispectral) WorldView-2 (WV-2) imagery. LiDAR point cloud data over San Francisco, California, USA, recorded in June 2010, was used to detect tree and building features by classifying point elevation values. The workflow employed includes resampling of LiDAR point cloud to generate a raster surface or digital terrain model (DTM), generation of a hill-shade image and an intensity image, extraction of digital surface model, generation of bare earth digital elevation model (DEM) and extraction of tree and building features. First, the optical WV-2 data and the LiDAR intensity image were co-registered using ground control points (GCPs). The WV-2 rational polynomial coefficients model (RPC) was executed in ERDAS Leica Photogrammetry Suite (LPS) using supplementary *.RPB file. In the second stage, ortho-rectification was carried out using ERDAS LPS by incorporating well-distributed GCPs. The root mean square error (RMSE) for the WV-2 was estimated to be 0.25 m by using more than 10 well-distributed GCPs. In the second stage, we generated the bare earth DEM from LiDAR point cloud data. In most of the cases, bare earth DEM does not represent true ground elevation. Hence, the model was edited to get the most accurate DEM/ DTM possible and normalized the LiDAR point cloud data based on DTM in order to reduce the effect of undulating terrain. We normalized the vegetation point cloud values by subtracting the ground points (DEM) from the LiDAR point cloud. A normalized digital surface model (nDSM) or CHM was calculated from the LiDAR data by subtracting the DEM from the DSM. The CHM or the normalized DSM represents the absolute height of all aboveground urban features relative to the ground. After normalization, the elevation value of a point indicates the height from the ground to the point. The above-ground points were used for tree feature and building footprint extraction. In individual tree extraction, first and last return point clouds were used along with the bare earth and building footprint models discussed above. In this study, scene dependent extraction criteria were employed to improve the 3D feature extraction process. LiDAR-based refining/ filtering techniques used for bare earth layer extraction were crucial for improving the subsequent 3D features (tree and building) feature extraction. The PAN-sharpened WV-2 image (with 0.5 m spatial resolution) was used to assess the accuracy of LiDAR-based 3D feature extraction. Our analysis provided an accuracy of 98 % for tree feature extraction and 96 % for building feature extraction from LiDAR data. This study could extract total of 15143 tree features using CHM method, out of which total of 14841 were visually interpreted on PAN-sharpened WV-2 image data. The extracted tree features included both shadowed (total 13830) and non-shadowed (total 1011). We note that CHM method could overestimate total of 302 tree features, which were not observed on the WV-2 image. One of the potential sources for tree feature overestimation was observed in case of those tree features which were adjacent to buildings. In case of building feature extraction, the algorithm could extract total of 6117 building features which were interpreted on WV-2 image, even capturing buildings under the trees (total 605) and buildings under shadow (total 112). Overestimation of tree and building features was observed to be limiting factor in 3D feature extraction process. This is due to the incorrect filtering of point cloud in these areas. One of the potential sources of overestimation was the man-made structures, including skyscrapers and bridges, which were confounded and extracted as buildings. This can be

  14. Dissolution effects and reef-like features in the Zechstein across the Mid North Sea High

    NASA Astrophysics Data System (ADS)

    Jenyon, Malcolm K.; Taylor, John C. M.

    Observations made in recent seismic data, combined with information from released wells, suggest that many structural features in the Zechstein interval across the Mid North Sea High are due to dissolution and removal of salt rock where it thinned against the upper flanks of the structure produced by the underlying High. It appears that radial run-off of intraformational, undersaturated.water from the culmination of the structure at the level of Post-Permian (Mesozoic) sediments has occurred. Salt-edge, and Salzspiegel-type areal dissolution both probably took place in some parts of the MNSH area. The complexity of the process was increased by the presence of Pre-Permian palaeogeomorphic features faults and horsts which interrupted, or modified, the intraformational drainage pattern. Subsequent settlement of the overlying Mesozoic sediments into the space vacated by the salt has revealed, through subsidence-drape, the presence of positive features resting on basal Zechstein units; certain of these features consist of material of much higher velocity than that of salt rock, and although they may be bryozoan-algal reefs from their form and location, it is equally possible that they may be primary or relict pods of anhydrite. Others are certainly Upper Carboniferous or Devonian horsts projecting up through the Zechstein interval. These horsts are of lower seismic velocity than the Zechstein interval material, which can be diagnostic.

  15. Feature Selection for high Dimensional DNA Microarray data using hybrid approaches.

    PubMed

    Kumar, Ammu Prasanna; Valsala, Preeja

    2013-01-01

    Feature selection from DNA microarray data is a major challenge due to high dimensionality in expression data. The number of samples in the microarray data set is much smaller compared to the number of genes. Hence the data is improper to be used as the training set of a classifier. Therefore it is important to select features prior to training the classifier. It should be noted that only a small subset of genes from the data set exhibits a strong correlation with the class. This is because finding the relevant genes from the data set is often non-trivial. Thus there is a need to develop robust yet reliable methods for gene finding in expression data. We describe the use of several hybrid feature selection approaches for gene finding in expression data. These approaches include filtering (filter out the best genes from the data set) and wrapper (best subset of genes from the data set) phases. The methods use information gain (IG) and Pearson Product Moment Correlation (PPMC) as the filtering parameters and biogeography based optimization (BBO) as the wrapper approach. K nearest neighbour algorithm (KNN) and back propagation neural network are used for evaluating the fitness of gene subsets during feature selection. Our analysis shows that an impressive performance is provided by the IG-BBO-KNN combination in different data sets with high accuracy (>90%) and low error rate. PMID:24143053

  16. Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin

    SciTech Connect

    Komura, Jun-ichiro; Ikehata, Hironobu; Mori, Toshio; Ono, Tetsuya

    2012-03-10

    During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. -- Highlights: Black-Right-Pointing-Pointer Global genome repair of (6-4) photoproducts is fully active in mitotic cells. Black-Right-Pointing-Pointer DNA in condensed mitotic chromatin does not seem inaccessible or inert. Black-Right-Pointing-Pointer Mitotic transcriptional repression may impair transcription-coupled repair.

  17. Mitotically active cellular fibroma of ovary should be differentiated from fibrosarcoma: a case report and review of literature

    PubMed Central

    Zong, Lin; Lin, Ming; Fan, Xinmin

    2014-01-01

    The clinicopathologic characteristic of mitotically active cellular fibroma is significantly different from the malignant behavior of ovarian fibrosarcoma. Therefore, its very important to differentiate mitotically active cellular fibroma from ovarian fibrosarcoma. We report a case in which a 39-year-old woman was found with an ovarian tumor measuring 105 71 47 mm. The tumor ruptured and adhered to the peritoneum. Microscopic examination showed densely cellular spindle-shaped tumor cells. The cellular atypia was mild. The Ki-67 proliferation index was approximately 10%. The patient remained free of tumor for more than 66 months without any adjuvant chemotherapy after operation. After reviewing the literature, we diagnosed this case as mitotically active cellular fibroma rather than ovarian fibrosarcoma. It is very important to differentiate these two tumors because of the marked differences in treatment modalities and prognosis between them. The ovarian fibrous tumors with mitotic figures ? 4 per 10 high-power fields but no severe nuclear atypia should be mostly diagnosed as mitotically active cellular fibroma of ovary. The correct diagnosis is the key to avoid excessive treatments. PMID:25550794

  18. Micromechanical-biochemical studies of mitotic chromosome elasticity and structure

    NASA Astrophysics Data System (ADS)

    Poirier, Michael Guy

    The structure of mitotic chromosomes was studied by combining micromechanical force measurements with microfluidic biochemical exposures. Our method is to use glass micropipettes attached to either end of a single chromosome to do mechanical experiments in the extracellular buffer. A third pipette can be used to locally 'spray' reactants so as to carry out dynamical mechanical-chemical experiments. The following elastic properties of mitotic chromosomes are found: Young's modulus, Y = 300 Pa; Poisson ratio, sigma = 0.1; Bending rigidity, B = 1 x 10 -22 Jm; Internal viscosity, eta' = 100 kg/msec; Volume fraction, ? = 0.7; Extensions of less than 3 times the relaxed length are linear and reversible; Extensions beyond 30 fold exhibit a force plateau at 15 nN and convert the chromosome to a disperse ghost-like state with little change in chromatin structure; Mitotic chromosomes are relatively isotropic; dsDNA cuts of at least every 3 kb cause the a mitotic chromosomes to fall apart; dsDNA cuts less frequently than every 50 kb do not affect mitotic chromosome structure. These results lead to the conclusion that mitotic chromosomes are a network crosslinked every 50 kb between which chromatin is fold by chromatin folding proteins, which are likely to be condensins.

  19. Targeting the Mitotic Catastrophe Signaling Pathway in Cancer

    PubMed Central

    Mc Gee, Margaret M.

    2015-01-01

    Mitotic catastrophe, as defined in 2012 by the International Nomenclature Committee on Cell Death, is a bona fide intrinsic oncosuppressive mechanism that senses mitotic failure and responds by driving a cell to an irreversible antiproliferative fate of death or senescence. Thus, failed mitotic catastrophe can promote the unrestrained growth of defective cells, thereby representing a major gateway to tumour development. Furthermore, the activation of mitotic catastrophe offers significant therapeutic advantage which has been exploited in the action of conventional and targeted anticancer agents. Yet, despite its importance in tumour prevention and treatment, the molecular mechanism of mitotic catastrophe is not well understood. A better understanding of the signals that determine cell fate following failed or defective mitosis will reveal new opportunities to selectively target and enhance the programme for therapeutic benefit and reveal biomarkers to predict patient response. This review is focused on the molecular mechanism of mitotic catastrophe induction and signalling and highlights current strategies to exploit the process in cancer therapy. PMID:26491220

  20. Timeless links replication termination to mitotic kinase activation.

    PubMed

    Dheekollu, Jayaraju; Wiedmer, Andreas; Hayden, James; Speicher, David; Gotter, Anthony L; Yen, Tim; Lieberman, Paul M

    2011-01-01

    The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication. PMID:21573113

  1. Interaction between TBP and Condensin Drives the Organization and Faithful Segregation of Mitotic Chromosomes.

    PubMed

    Iwasaki, Osamu; Tanizawa, Hideki; Kim, Kyoung-Dong; Yokoyama, Yuhki; Corcoran, Christopher J; Tanaka, Atsunari; Skordalakes, Emmanuel; Showe, Louise C; Noma, Ken-Ichi

    2015-09-01

    Genome/chromosome organization is highly ordered and controls various nuclear events, although the molecular mechanisms underlying the functional organization remain largely unknown. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosomal organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation. PMID:26257282

  2. Rabbit System. Low cost, high reliability front end electronics featuring 16 bit dynamic range

    NASA Astrophysics Data System (ADS)

    Drake, G.; Droege, T. F.; Nelson, C. A., Jr.; Turner, K. J.; Ohska, T. K.

    1985-10-01

    A new crate-based front end system has been built which features low cost, compact packaging, command capability, 16 bit dynamic range digitization, and a high degree of redundancy. The crate can contain a variety of instrumentation modules, and is designed to be situated close to the detector. The system is suitable for readout of a large number of channels via parallel multiprocessor data acquisition.

  3. Fabrication of Pt nanowires with a diffraction-unlimited feature size by high-threshold lithography

    NASA Astrophysics Data System (ADS)

    Li, Li; Wang, Zuobin; Li, Wenjun; Peng, Kuiqing; Zhang, Ziang; Yu, Miao; Song, Zhengxun; Weng, Zhankun; Wang, Dapeng; Zhao, Le

    2015-09-01

    Although the nanoscale world can already be observed at a diffraction-unlimited resolution using far-field optical microscopy, to make the step from microscopy to lithography still requires a suitable photoresist material system. In this letter, we consider the threshold to be a region with a width characterized by the extreme feature size obtained using a Gaussian beam spot. By narrowing such a region through improvement of the threshold sensitization to intensity in a high-threshold material system, the minimal feature size becomes smaller. By using platinum as the negative photoresist, we demonstrate that high-threshold lithography can be used to fabricate nanowire arrays with a scalable resolution along the axial direction of the linewidth from the micro- to the nanoscale using a nanosecond-pulsed laser source with a wavelength ?0 = 1064 nm. The minimal feature size is only several nanometers (sub ?0/100). Compared with conventional polymer resist lithography, the advantages of high-threshold lithography are sharper pinpoints of laser intensity triggering the threshold response and also higher robustness allowing for large area exposure by a less-expensive nanosecond-pulsed laser.

  4. Glacial Features in the Western Gulf of Maine Inferred From High Resolution Bathymetric Data

    NASA Astrophysics Data System (ADS)

    Malik, M. A.; Licciardi, J. M.; Ward, L. G.; Mayer, L. A.

    2007-12-01

    Multibeam sonar surveys in the last decade have revealed submerged glacial features in the western Gulf of Maine (e.g., Valentine et al., 2003). Here we examine high-resolution multibeam bathymetric data acquired in 2001 and 2005 over Jeffreys Ledge to infer the origin of previously unrecognized small-scale marine glacial features. Ridges as high as 5 m appear throughout the length of Jeffreys Ledge in water depths of ~50 m. Bottom photographs of these features show boulders of up to 50 cm diameter in a flat sandy bottom devoid of finer material. These ridges are probably recessional moraines that have been reworked during lower relative sea level (~55 m below modern sea level). The moraine-like features imply stabilization of an ice margin along the length of Jeffreys Ledge. The central portion of Jeffreys Ledge also contains asymmetrical dune forms with a relief of 1-6 m and along-crest orientations trending NW-SE. These dunes may have formed during megaflood events with water flow toward the southwest. Streamlined bathymetric features with a relief of ~8 m and lengths up to 700 m occur east of Jeffreys Ledge. These features have similar dimensions but different orientations (N-S), as compared to southeast-oriented drumlins identified south of Cape Ann by Oldale et al. (1994). Dissimilar orientations of these drumlins are consistent with the lobate shape of the ice sheet and probable local ice flow directions. Numerous iceberg scours were observed in the basins east of Stellwagen Bank and Jeffreys Ledge with varying widths (50-300 m), scour depths (1-5 m) and lengths (3-10 km). Two dominant orientations of iceberg scours (E- W and N-S) were identified. Additional data such as seismic profiles, bottom photographs and bottom samples will further define the origin of these small-scale glacial features. Oldale, R.N., Knebel, H.J., Bothner, M.H., 1994, Geomorphology 9, 301-309. Valentine, P., Unger, T., Baker, J., 2003, U.S. Geological Survey Geologic Investigations Series Map I-2676C, scale 1:60,000.

  5. Increased functional protein expression using nucleotide sequence features enriched in highly expressed genes in zebrafish

    PubMed Central

    Horstick, Eric J.; Jordan, Diana C.; Bergeron, Sadie A.; Tabor, Kathryn M.; Serpe, Mihaela; Feldman, Benjamin; Burgess, Harold A.

    2015-01-01

    Many genetic manipulations are limited by difficulty in obtaining adequate levels of protein expression. Bioinformatic and experimental studies have identified nucleotide sequence features that may increase expression, however it is difficult to assess the relative influence of these features. Zebrafish embryos are rapidly injected with calibrated doses of mRNA, enabling the effects of multiple sequence changes to be compared in vivo. Using RNAseq and microarray data, we identified a set of genes that are highly expressed in zebrafish embryos and systematically analyzed for enrichment of sequence features correlated with levels of protein expression. We then tested enriched features by embryo microinjection and functional tests of multiple protein reporters. Codon selection, releasing factor recognition sequence and specific introns and 3′ untranslated regions each increased protein expression between 1.5- and 3-fold. These results suggested principles for increasing protein yield in zebrafish through biomolecular engineering. We implemented these principles for rational gene design in software for codon selection (CodonZ) and plasmid vectors incorporating the most active non-coding elements. Rational gene design thus significantly boosts expression in zebrafish, and a similar approach will likely elevate expression in other animal models. PMID:25628360

  6. Development of a virtual probe tip with an application to high aspect ratio microscale features

    SciTech Connect

    Bauza, Marcin B.; Hocken, Robert J.; Smith, Stuart T.; Woody, Shane C.

    2005-09-15

    Nondestructive measurement of microscale features remains a challenging metrology problem. For example, to assess a high aspect ratio small hole it is currently common to cut a cross section and measure the features of interest using an atomic force microscope, scanning probe microscope, or scanning electron microscope. Typically, these metrology tools may be suitable for surface finish measurement but often lack the capability for dimensional metrology. The aim of this article is to discuss the development of a high aspect-ratio microscale probe for measurement of microscale features. A 700:1 high aspect ratio probe shank is fabricated with a 7 {mu}m diameter, and attached at one end to an oscillator. The oscillator produces a standing wave in the oscillating probe shank as opposed to conventional probes that use a microscale sphere on the end of a comparatively rigid shank. As a result of the standing wave formed in steady state vibration, the free end of the shank generates an amplitude of oscillation greater than the probe shank diameter. Thus, the probe does not require a spherical ball to serve as the contact point and simply uses the contact diameter of the free end of the vibrating shank. This methodology is referred to as a virtual probe tip. The virtual probe tip in conjunction with a nanopositioning scanner is used to measure surface profile measurements over traverse lengths of 130 {mu}m. In this article, results from profiles of a 500 nm step height and a ruby sphere of diameter 1 mm are presented. Experiments in this article indicate the ability to repeatedly resolve surface features of less than 5 nm while maintaining bandwidths greater than 1 kHz. Furthermore, adhesion problems often encountered with micrometer scaled probes were not observed during profile measurements with this virtual probe.

  7. High-resolution digital elevation models of the Flade Iceblink feature in NE Greenland

    NASA Astrophysics Data System (ADS)

    Willis, M. J.; Juntunen, T.; Porter, C. C.; Morin, P. J.

    2013-12-01

    We produce a time series of high-resolution digital elevation models (DEM) to examine the recent evolution of an 8.7 km2 sub-glacial lake collapse feature near the southern summit of the 8500 km2 Flade Isblink Ice Cap (FIIC) in northeastern Greenland [Figure 1]. Visible imagery from the MODerate-resolution Imaging Spectroradiometer (MODIS) indicates the collapse occurred between August 16th and September 6th, 2011 at the site of a recurring moulin. DEMs are extracted using the NASA Ames Stereo Pipeline for the period between June 2012 and late 2013 from 0.5 m resolution along-track stereo image pairs available via the NGA commercial imagery program. The DEMs are compared to a 1996 ERS InSAR derived DEM [Palmer et al., 2010], and to a contemporary airborne laser altimeter swath flown by NASA Icebridge in mid-April 2013 to derive the volume of the feature and the uncertainties on the high-resolution DEMs. The 'mitten' shaped feature is bounded by crevasses on three sides, with a shallow ramp to the south. It is ~70 m deep, 3.7 km north-to-south and 3 km east-to-west and has a volume of ~0.3 km3. Ice penetrating radar from a nearby Icebridge mission in May 2011, indicates the ice is approximately 550 m thick and that the bed is very flat and smooth about 1 km to the southeast of the feature. The nearby bed topography, local geology and lack of recorded seismicity in the area indicate it is unlikely that the feature is the result of either subglacial volcanic activity or the collapse of a limestone karst feature below the ice cap - the neighboring Princess Elizabeth Alps are composed of 420 Ma Caledonide fold belt gneisses. The presence of recurring supraglacial meltwater streams and drainage into the feature, its rapid formation and its steep sided nature instead suggest that it formed during the rapid drainage of a sub-glacial lake - which is, as far as we are aware, the first recorded instance of such an occurrence in Greenland. Meltwater observed using 250 m resolution MODIS imagery during the extensive melt seasons of both 2010 and 2011 flows northwards into the area of the feature before disappearing - presumably down a Moulin. We use RACMO2 to provide rough estimates of the volumes involved. We monitor the elevation of the floor of the feature to see if the subglacial lake is refilling and provide gross, low-resolution estimates of hydraulic head and drainage path calculations for the region. Flade Iceblink feature from IceBridge. Michael Studdinger/NASA mike.willis@cornell.edu Flade Ice Blink as taken by Michael Studdinger/NASA

  8. Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos.

    PubMed

    McCoy, Rajiv C; Demko, Zachary; Ryan, Allison; Banjevic, Milena; Hill, Matthew; Sigurjonsson, Styrmir; Rabinowitz, Matthew; Fraser, Hunter B; Petrov, Dmitri A

    2015-04-10

    Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency. PMID:25859044

  9. Mechanism and Regulation of Kinesin-5, an essential motor for the mitotic spindle

    PubMed Central

    Waitzman, Joshua S.; Rice, Sarah E.

    2014-01-01

    Mitotic cell division is the most fundamental task of all living cells. Cells have intricate and tightly regulated machinery to ensure that mitosis occurs with appropriate frequency and high fidelity. A core element of this machinery is the kinesin-5 motor protein, which plays essential roles in spindle formation and maintenance. In this review, we discuss how the structural and mechanical properties of kinesin-5 motors uniquely suit them to their mitotic role. We describe some of the small molecule inhibitors and regulatory proteins that act on kinesin-5, and discuss how these regulators may influence the process of cell division. Finally, we touch on some more recently described functions of kinesin-5 motors in non-dividing cells. Throughout, we highlight a number of open questions that impede our understanding of both this motor's function and the potential utility of kinesin-5 inhibitors. PMID:24125467

  10. Feature extraction and classification of clouds in high resolution panchromatic satellite imagery

    NASA Astrophysics Data System (ADS)

    Sharghi, Elan

    The development of sophisticated remote sensing sensors is rapidly increasing, and the vast amount of satellite imagery collected is too much to be analyzed manually by a human image analyst. It has become necessary for a tool to be developed to automate the job of an image analyst. This tool would need to intelligently detect and classify objects of interest through computer vision algorithms. Existing software called the Rapid Image Exploitation Resource (RAPIER) was designed by engineers at Space and Naval Warfare Systems Center Pacific (SSC PAC) to perform exactly this function. This software automatically searches for anomalies in the ocean and reports the detections as a possible ship object. However, if the image contains a high percentage of cloud coverage, a high number of false positives are triggered by the clouds. The focus of this thesis is to explore various feature extraction and classification methods to accurately distinguish clouds from ship objects. An examination of a texture analysis method, line detection using the Hough transform, and edge detection using wavelets are explored as possible feature extraction methods. The features are then supplied to a K-Nearest Neighbors (KNN) or Support Vector Machine (SVM) classifier. Parameter options for these classifiers are explored and the optimal parameters are determined.

  11. Spectral feature design for data compression in high dimensional multispectral data

    NASA Technical Reports Server (NTRS)

    Chen, C.-C. Thomas; Landgrebe, David A.

    1987-01-01

    Data transmission loads of high dimensional remote sensor systems can be greatly reduced by applying generalized Karhunen-Loeve transform as a feature design technique. Two spectral feature design approaches based upon the generalized K-L transform are developed to compress information effectively. Six sets of field data from Kansas and North Dakota on three different dates each are used to test the methods. Spatially, temporally and spatially/temporally combined data sets are formed in this paper to test the robustness property of the schemes. The probability of correct classification using Landsat MSS, Thematic Mapper bands and the proposed bands are found and compared. The comparison shows that the results are improved by the proposed methods, and they appear to be satisfactorily robust. The overall data compression ratio in this paper is about 100/16, i.e., about 6 to 1 with no loss in classification accuracy.

  12. Cold-treated centrosome: isolation of centrosomes from mitotic sea urchin eggs, production of an anticentrosomal antibody, and novel ultrastructural imaging.

    PubMed

    Thompson-Coffe, C; Coffe, G; Schatten, H; Mazia, D; Schatten, G

    1996-01-01

    A novel isolation of centrosomes is described and it was used to both generate a centrosome-specific monoclonal antibody and to image with high-resolution low-voltage scanning electron microscopy the surface details of the isolated centrosome. At first mitotic prometaphase, sea urchin zygotes are chilled on ice overnight. While most of the microtubules disassemble, the mitotic centrosomes collapse into aggregated masses. These centrosomes have been isolated, and used to generate a monoclonal antibody, designated 4D2, which is reactive with interphase and mitotic centrosomes. 4D2 staining of centrosomes is similar, but not identical, to that of other centrosomal antibodies like Ah6 and 5051. Centrosomal material is detected as a compact sphere after cold treatment; upon recovery the sphere expands and undergoes the shape changes previously described [Mazia et al., 1987: J. Cell Biol. 105:206a] to eventually reorganize a normal mitotic apparatus. PMID:8674139

  13. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    PubMed Central

    Plitt, Mark; Barnes, Kelly Anne; Martin, Alex

    2014-01-01

    Objectives Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication. Results High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning. Conclusions While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing. PMID:25685703

  14. Detection and Mapping of Sedimentary Features on Alluvial Fans Using High-Resolution Overhead Thermal Imaging

    NASA Astrophysics Data System (ADS)

    Hardgrove, C. J.; Moersch, J. E.; Whisner, S.

    2008-12-01

    In this study we evaluate the utility of thermal imagery for revealing geomorphic features and evidence of sedimentary processes on the surfaces of alluvial fans. Prior studies of alluvial fans have made extensive use of visible imagery and traditional field-based mapping techniques to identify surface geomorphic features and sedimentary processes. Here we present a comparison of features mapped using thermal images acquired from the ground, a light aircraft (altitude ~5000 ft, resolution ~2 m/pixel) and ASTER satellite imagery (resolution 90 m/pixel), to a preexisting ground-based map of features on an example alluvial fan in Owens Valley, California. Thermal images from a light aircraft were acquired at several times of day to determine how the surface temperatures of the alluvial fan rise and fall throughout a diurnal cycle. We have also acquired thermal images of the same fan from the ground at 5 minute intervals over the course of a full diurnal cycle. ASTER thermal data also covers the Owens Valley, and was used to determine if this technique can be used from orbit at significantly lower resolution (90 m/pixel). In an arid climate with low vegetation cover, the temperature of a surface at any given time of day is a complex function of many parameters, including slope, azimuth, composition, degree of induration, and grain size. By analyzing the temperatures on the surface of an alluvial fan with comparable slopes, azimuth, and composition, we make estimates of the relative particle size or degree of induration. We utilize the fact that several sedimentary processes acting on the surface of alluvial fans sort particles by size. For example, both debris flow and channelized flow processes can form linear features of large and small clasts. Therefore, thermal imagery could be expected to reveal evidence of these processes at the surfaces of alluvial fans in the form of spatial patterns of surface thermal properties. Process-related sedimentary features, such as clast-rich and clast-poor debris flows, debris-flow levees, and the change in particle size at the toe of the fan are all clearly revealed in the aerial thermal images of the Dolomite Fan in Owens Valley, California. The locations of these features in the thermal imagery match the locations of the features as mapped using traditional ground-based field sedimentology techniques by Blair and McPherson (1998). All debris flows that are exposed at the fan surface are evident in the aerial thermal imagery, including those that have been heavily weathered and are difficult to observe in visible aerial or orbital imagery. ASTER satellite thermal image data does not show the same sedimentary features as our aerial thermal images, presumably due to the significantly poorer spatial resolution of the satellite data. Our aerial thermal imagery suggests that higher resolution satellite data from a future satellite experiment could be used to detect sedimentary processes on alluvial fans anywhere on Earth. High resolution thermal imagery from above can be used to provide preliminary reconnaissance of an alluvial fan, suggest what processes have most recently acted on the surface of the fan, and to prioritize sites for detailed study on the ground. Future work will expand our database of alluvial fans and the list of process-related surface features that can be identified with thermal imagery.

  15. Promotion of chloroplast proliferation upon enhanced post-mitotic cell expansion in leaves

    PubMed Central

    2013-01-01

    Background Leaves are determinate organs; hence, precise control of cell proliferation and post-mitotic cell expansion is essential for their growth. A defect in cell proliferation often triggers enhanced post-mitotic cell expansion in leaves. This phenomenon is referred to as ‘compensation’. Several lines of evidence from studies on compensation have shown that cell proliferation and post-mitotic cell expansion are coordinately regulated during leaf development. Therefore, compensation has attracted much attention to the mechanisms for leaf growth. However, our understanding of compensation at the subcellular level remains limited because studies of compensation have focused mainly on cellular-level phenotypes. Proper leaf growth requires quantitative control of subcellular components in association with cellular-level changes. To gain insight into the subcellular aspect of compensation, we investigated the well-known relationship between cell area and chloroplast number per cell in compensation-exhibiting lines, and asked whether chloroplast proliferation is modulated in response to the induction of compensation. Results We first established a convenient and reliable method for observation of chloroplasts in situ. Using this method, we analyzed Arabidopsis thaliana mutants fugu5 and angustifolia3 (an3), and a transgenic line KIP-RELATED PROTEIN2 overexpressor (KRP2 OE), which are known to exhibit typical features of compensation. We here showed that chloroplast number per cell increased in the subepidermal palisade tissue of these lines. We analyzed tetraploidized wild type, fugu5, an3 and KRP2 OE, and found that cell area itself, but not nuclear ploidy, is a key parameter that determines the activity of chloroplast proliferation. In particular, in the case of an3, we uncovered that promotion of chloroplast proliferation depends on the enhanced post-mitotic cell expansion. The expression levels of chloroplast proliferation-related genes are similar to or lower than that in the wild type during this process. Conclusions This study demonstrates that chloroplast proliferation is promoted in compensation-exhibiting lines. This promotion of chloroplast proliferation takes place in response to cell-area increase in post-mitotic phase in an3. The expression of chloroplast proliferation-related genes were not promoted in compensation-exhibiting lines including an3, arguing that an as-yet-unknown mechanism is responsible for modulation of chloroplast proliferation in these lines. PMID:24074400

  16. Mitotic catastrophe and cell death induced by depletion of centrosomal proteins

    PubMed Central

    Kimura, M; Yoshioka, T; Saio, M; Banno, Y; Nagaoka, H; Okano, Y

    2013-01-01

    Mitotic catastrophe, which refers to cell death or its prologue triggered by aberrant mitosis, can be induced by a heterogeneous group of stimuli, including chromosome damage or perturbation of the mitotic apparatus. We investigated the mechanism of mitotic catastrophe and cell death induced by depletion of centrosomal proteins that perturbs microtubule organization. We transfected cells harboring wild-type or mutated p53 with siRNAs targeting Aurora A, ninein, TOG, TACC3, ?-tubulin, or pericentriolar material-1, and monitored the effects on cell death. Knockdown of Aurora A, ninein, TOG, and TACC3 led to cell death, regardless of p53 status. Knockdown of Aurora A, ninein, and TOG, led to aberrant spindle formation and subsequent cell death, which was accompanied by several features of apoptosis, including nuclear condensation and Annexin V binding in HeLa cells. During this process, cleavage of poly(ADP-ribose) polymerase-1, caspase-3, and caspase-9 was detected, but cleavage of caspase-8 was not. Cell death, monitored by time-lapse imaging, occurred during both interphase and M phase. In cells depleted of a centrosomal protein (Aurora A, ninein, or TOG), the rate of cell death was higher if the cells were cotransfected with siRNA against BubR1 or Mad2 than if they were transfected with siRNA against Bub1 or a control siRNA. These results suggest that metaphase arrest is necessary for the mitotic catastrophe and cell death caused by depletion of centrosomal proteins. Knockdown of centrosomal proteins led to increased phosphorylation of Chk2. Enhanced p-Chk2 localization was also observed at the centrosome in cells arrested in M phase, as well as in the nuclei of dying cells. Cotransfection of siRNAs against Chk2, in combination with depletion of a centrosomal protein, decreased the amount of cell death. Thus, Chk2 activity is indispensable for apoptosis after mitotic catastrophe induced by depletion of centrosomal proteins that perturbs microtubule organization. PMID:23598415

  17. Automated Identification of River Hydromorphological Features Using UAV High Resolution Aerial Imagery

    PubMed Central

    Rivas Casado, Monica; Ballesteros Gonzalez, Rocio; Kriechbaumer, Thomas; Veal, Amanda

    2015-01-01

    European legislation is driving the development of methods for river ecosystem protection in light of concerns over water quality and ecology. Key to their success is the accurate and rapid characterisation of physical features (i.e., hydromorphology) along the river. Image pattern recognition techniques have been successfully used for this purpose. The reliability of the methodology depends on both the quality of the aerial imagery and the pattern recognition technique used. Recent studies have proved the potential of Unmanned Aerial Vehicles (UAVs) to increase the quality of the imagery by capturing high resolution photography. Similarly, Artificial Neural Networks (ANN) have been shown to be a high precision tool for automated recognition of environmental patterns. This paper presents a UAV based framework for the identification of hydromorphological features from high resolution RGB aerial imagery using a novel classification technique based on ANNs. The framework is developed for a 1.4 km river reach along the river Dee in Wales, United Kingdom. For this purpose, a Falcon 8 octocopter was used to gather 2.5 cm resolution imagery. The results show that the accuracy of the framework is above 81%, performing particularly well at recognising vegetation. These results leverage the use of UAVs for environmental policy implementation and demonstrate the potential of ANNs and RGB imagery for high precision river monitoring and river management. PMID:26556355

  18. Automated Identification of River Hydromorphological Features Using UAV High Resolution Aerial Imagery.

    PubMed

    Casado, Monica Rivas; Gonzalez, Rocio Ballesteros; Kriechbaumer, Thomas; Veal, Amanda

    2015-01-01

    European legislation is driving the development of methods for river ecosystem protection in light of concerns over water quality and ecology. Key to their success is the accurate and rapid characterisation of physical features (i.e., hydromorphology) along the river. Image pattern recognition techniques have been successfully used for this purpose. The reliability of the methodology depends on both the quality of the aerial imagery and the pattern recognition technique used. Recent studies have proved the potential of Unmanned Aerial Vehicles (UAVs) to increase the quality of the imagery by capturing high resolution photography. Similarly, Artificial Neural Networks (ANN) have been shown to be a high precision tool for automated recognition of environmental patterns. This paper presents a UAV based framework for the identification of hydromorphological features from high resolution RGB aerial imagery using a novel classification technique based on ANNs. The framework is developed for a 1.4 km river reach along the river Dee in Wales, United Kingdom. For this purpose, a Falcon 8 octocopter was used to gather 2.5 cm resolution imagery. The results show that the accuracy of the framework is above 81%, performing particularly well at recognising vegetation. These results leverage the use of UAVs for environmental policy implementation and demonstrate the potential of ANNs and RGB imagery for high precision river monitoring and river management. PMID:26556355

  19. Robust mitotic entry is ensured by a latching switch

    PubMed Central

    Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novk, Bla

    2013-01-01

    Summary Cell cycle events are driven by Cyclin dependent kinases (CDKs) and by their counter-acting phosphatases. Activation of the Cdk1:Cyclin B complex during mitotic entry is controlled by the Wee1/Myt1 inhibitory kinases and by Cdc25 activatory phosphatase, which are themselves regulated by Cdk1:Cyclin B within two positive circuits. Impairing these two feedbacks with chemical inhibitors induces a transient entry into M phase referred to as mitotic collapse. The pathology of mitotic collapse reveals that the positive circuits play a significant role in maintaining the M phase state. To better understand the function of these feedback loops during G2/M transition, we propose a simple model for mitotic entry in mammalian cells including spatial control over Greatwall kinase phosphorylation. After parameter calibration, the model is able to recapture the complex and non-intuitive molecular dynamics reported by Potapova et al. (Potapova et al., 2011). Moreover, it predicts the temporal patterns of other mitotic regulators which have not yet been experimentally tested and suggests a general design principle of cell cycle control: latching switches buffer the cellular stresses which accompany cell cycle processes to ensure that the transitions are smooth and robust. PMID:24143279

  20. Mitotic Chromosome Loss in a Disomic Haploid of SACCHAROMYCES CEREVISIAE

    PubMed Central

    Campbell, D. A.; Fogel, S.; Lusnak, K.

    1975-01-01

    Experiments designed to characterize the incidence of mitotic chromosome loss in a yeast disomic haploid were performed. The selective methods employed utilize the non-mating property of strains disomic for linkage group III and heterozygous at the mating type locus. The principal findings are: (1) The frequency of spontaneous chromosome loss in the disome is of the order 10-4 per cell; this value approximates the frequency in the same population of spontaneous mitotic exchange resulting in homozygosity at the mating type locus. (2) The recovered diploids are pure clones, and thus represent unique events in the disomic haploid. (3) Of the euploid chromosomes recovered after events leading to chromosome loss, approximately 90% retain the parental marker configuration expected from segregation alone; however, the remainder are recombinant for marker genes, and are the result of mitotic exchanges in the disome, especially in regions near the centromere. The recombinant proportion significantly exceeds that expected if chromosome loss and mitotic exchange in the disome were independent events. The data are consistent with a model proposing mitotic nondisjunction as the event responsible for chromosome loss in the disomic haploid. PMID:1092597

  1. Mechanical control of mitotic progression in single animal cells

    PubMed Central

    Cattin, Cedric J.; Dggelin, Marcel; Martinez-Martin, David; Gerber, Christoph; Mller, Daniel J.; Stewart, Martin P.

    2015-01-01

    Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedbackcontrolled confinement of single cells while characterizing their progression through mitosis. We identify three force regimes according to the cell response: small forces (?5 nN) that accelerate mitotic progression, intermediate forces where cells resist confinement (50100 nN), and yield forces (>100 nN) where a significant decline in cell height impinges on microtubule spindle function, thereby inhibiting mitotic progression. Yield forces are coincident with a nonlinear drop in cell height potentiated by persistent blebbing and loss of cortical F-actin homogeneity. Our results suggest that a buildup of actomyosin-dependent cortical tension and intracellular pressure precedes mechanical failure, or herniation, of the cell cortex at the yield force. Thus, we reveal how the mechanical properties of mitotic cells and their response to external forces are linked to mitotic progression under conditions of mechanical confinement. PMID:26305930

  2. Dynamics and inherent safety features of small modular high temperature gas-cooled reactors

    SciTech Connect

    Harrington, R.M.; Ball, S.J.; Cleveland, J.C.

    1986-01-01

    Investigations were made at Oak Ridge National Laboratory to characterize the dynamics and inherent safety features of various modular high temperature gas-cooled reactor (HTGR) designs. This work was sponsored by the US Nuclear Regulatory Commission's HTGR Safety Research program. The US Department of Energy (DOE) and the Gas Cooled Reactor Associates (GCRA) have sponsored studies of several modular HTGR concepts, each having it own unique advantageous economic and inherent safety features. The DOE design team has recently choses a 350-MW(t) annular core with prismatic, graphite matrix fuel for its reference plant. The various safety features of this plant and of the pebble-bed core designs similar to those currently being developed and operated in the Federal Republic of Germany (FRG) are described. A varity of postulated accident sequences involving combinations of loss of forced circulation of the helium primary coolant, loss of primary coolant pressurization, and loss of normal and backup heat sinks were studied and are discussed. Results demonstrate that each concept can withstand an uncontrolled heatup accident without reaching excessive peak fuel temperatures. Comparisons of calculated and measured response for a loss of forced circulation test on the FRG reactor, AVR, are also presented. 10 refs.

  3. Plasma etching of high-resolution features in a fullerene molecular resist

    NASA Astrophysics Data System (ADS)

    Manyam, J.; Manickam, M.; Preece, J. A.; Palmer, R. E.; Robinson, A. P. G.

    2011-04-01

    As resist films become thinner, so as to reduce problems of aspect ratio related pattern collapse at high-resolution, it is becoming increasingly difficult to transfer patterns with useful aspect ratio by directly etching the resist. It has become common to use the photoresist to pattern an intermediate hardmask, which then protects the silicon substrate during etching, allowing useful aspect ratios but adding process complexity. We have previously described a fullerene based electron beam lithography resist capable of 20 nm halfpitch and 12 nm sparse features, at a sensitivity of less than 10 ?C/cm2 at 20 keV. The fullerene resist has high etch durability - comparable to that of commercial novolac resists - and has previously demonstrated an etch selectivity of 3:1 to silicon using electron cyclotron resonance microwave plasma etching with SF6. Here a study of the capabilities of this resist when using Inductively Coupled Plasma etching is presented. Line-space patterns with half-pitches in the range 25 nm to 100 nm, together with sparse features (~20 nm linewidth on a 200 nm pitch) were produced in ~30 nm thick resist films using electron beam lithography, and transferred to silicon using an inductively coupled plasma etcher. Several combinations of SF6, CF4, CHF3 and C4F8process gases were explored. Etch selectivity and anisotropy were studied as a range of etching parameters, such as ICP and RF power, gas flow rate, pressure and temperature were varied. Etch selectivities in excess of 9:1 were demonstrated. Techniques for minimizing aspect ratio dependent etching effects in dense features, including the use of ashing or high etching pressures were also examined.

  4. Angiomyofibroblastoma of the vulva: a mitotically active variant?

    PubMed

    Takeshima, Y; Shinkoh, Y; Inai, K

    1998-04-01

    A case of angiomyofibroblastoma in a 48-year-old woman is reported. The tumor occurred as a left vulval mass and was treated by simple excision. It was located in the subcutaneous tissue of the left vulva and was well circumscribed, measuring 2.8 x 2.7 x 2.5 cm. Microscopically, the tumor was composed of hypocellular and cellular areas with well-developed small vessels. Spindle or polygonal cells were arranged with perivascular accentuation in an edematous or fibrocollagenous background. Some spindle-shaped or polygonal stromal cells were also arranged in epithelioid nests. In some areas, mitoses were frequent (maximum 3/10 high-power field). Immunohistochemically, the stromal cells were positive for vimentin and desmin, but negative for alpha-smooth muscle actin, S-100, neurofilament, estrogen receptor, progesterone receptor, CD31 and CD34. The average labeling index of Ki-67 in stromal cells was 3.1%. Ultrastructural analysis demonstrated that the stromal cells adhered with primitive junctions and contained intermediate filaments with no focal density in the cytoplasm. These findings were consistent with angiomyofibroblastoma, although previously reported cases did not show so many mitoses. Therefore, this case was suggested to be a mitotically active variant. PMID:9648158

  5. Centrin: Another target of monastrol, an inhibitor of mitotic spindle

    NASA Astrophysics Data System (ADS)

    Duan, Lian; Wang, Tong-Qing; Bian, Wei; Liu, Wen; Sun, Yue; Yang, Bin-Sheng

    2015-02-01

    Monastrol, a cell-permeable inhibitor, considered to specifically inhibit kinesin Eg5, can cause mitotic arrest and monopolar spindle formation, thus exhibiting antitumor properties. Centrin, a ubiquitous protein associated with centrosome, plays a critical role in centrosome duplication. Moreover, a correlation between centrosome amplification and cancer has been reported. In this study, it is proposed for the first time that centrin may be another target of the anticancer drug monastrol since monastrol can effectively inhibit not only the growth of the transformed Escherichia coli cells in vivo, but also the Lu3+-dependent self-assembly of EoCen in vitro. The two closely related compounds (Compounds 1 and 2) could not take the same effect. Fluorescence titration experiments suggest that four monastrols per protein is the optimum binding pattern, and the binding constants at different temperatures were obtained. Detailed thermodynamic analysis indicates that hydrophobic force is the main acting force between monastrol and centrin, and the extent of monastrol inhibition of centrin self-assembly is highly dependent upon the hydrophobic region of the protein, which is largely exposed by the binding of metal ions.

  6. Cyclic development of igneous features and their relationship to high-temperature hydrothermal features in the Henderson porphyry molybdenum deposit, Colorado

    USGS Publications Warehouse

    Carten, R.B.; Geraghty, E.P.; Walker, B.M.

    1988-01-01

    The Henderson porphyry molybdenum deposit was formed by the superposition of coupled alteration and mineralization events, of varying intensity and size, that were associated with each of at least 11 intrusions. Deposition of molybdenite was accompanied by time-equivalent silicic and potassic alteration. High-temperature alteration and mineralization are spatially and temporally linked to the crystallization of compositionally zoned magma in the apex of stocks. Differences in hydrothermal features associated with each intrusion (e.g., mass of ore, orientation and type of veins, density of veins, and intensity of alteration) correlate with differences in primary igneous features (e.g., composition, texture, morphology, and size). The systematic relations between hydrothermal and magmatic features suggest that primary magma compositions, including volatile contents, largely control the geometry, volume, level of emplacement, and mechanisms of crystallization of stocks. These elements in turn govern the orientations and densities of fractures, which ultimately determine the distribution patterns of hydrothermal alteration and mineralization. -from Authors

  7. Specific features of diffuse photon migration in highly scattering media with optical properties of biological tissues

    NASA Astrophysics Data System (ADS)

    Proskurin, S. G.; Potlov, A. Yu; Frolov, S. V.

    2015-06-01

    Specific features of motion of photon density normalised maximum (PDNM) of pulsed radiation in highly scattering media with optical properties of biological tissues are described. A numerical simulation has confirmed that, when the object is a homogeneous cylinder, PDNM always moves to its geometric centre. In the presence of an absorbing inhomogeneity, PDNM moves towards the point symmetric to the geometric centre of the inhomogeneity with respect to the centre of the cylindrical object. In the presence of a scattering inhomogeneity, PDNM moves towards its geometric centre.

  8. DESIGN SAFETY FEATURES OF THE BNL HIGH-TEMPERATURE COMBUSTION FACILITY

    SciTech Connect

    GINSBERG,T.; CICCARELLI,G.; BOCCIO,J.

    2000-06-11

    The Brookhaven National Laboratory (BNL) High-Temperature Combustion Facility (HTCF) was used to perform hydrogen deflagration and detonation experiments at temperatures to 650 K. Safety features that were designed to ensure safe and reliable operation of the experimental program are described. Deflagration and detonation experiments have been conducted using mixtures of hydrogen, air, and steam. Detonation cell size measurements were made as a function of mixture composition and thermodynamic gas conditions. Deflagration-to-detonation transition experiments were also conducted. Results of the experimental program are presented, and implications with respect to hydrogen safety are discussed.

  9. Synergistic Blockade of Mitotic Exit by Two Chemical Inhibitors of the APC/C

    PubMed Central

    Sackton, Katharine L.; Dimova, Nevena; Zeng, Xing; Tian, Wei; Zhang, Mengmeng; Sackton, Timothy B.; Meaders, Johnathan; Pfaff, Kathleen L.; Sigoillot, Frederic; Yu, Hongtao; Luo, Xuelian; King, Randall W.

    2014-01-01

    Summary Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the Anaphase-Promoting Complex/Cyclosome (APC/C), a thirteen-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome1,2. Because blocking mitotic exit is an effective approach for inducing tumor cell death3,4, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc205, which forms a co-receptor with the APC/C to recognize substrates containing a Destruction box (D-box)6-14. Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identified a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-L-arginine methyl ester (TAME), a small molecule that blocks the APC/C-Cdc20 interaction15,16. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine. PMID:25156254

  10. p21-activated kinase 4 regulates mitotic spindle positioning and orientation.

    PubMed

    Bompard, Guillaume; Morin, Nathalie

    2012-01-01

    During mitosis, microtubules (MTs) are massively rearranged into three sets of highly dynamic MTs that are nucleated from the centrosomes to form the mitotic spindle. Tight regulation of spindle positioning in the dividing cell and chromosome alignment at the center of the metaphase spindle are required to ensure perfect chromosome segregation and to position the cytokinetic furrow that will specify the two daughter cells. Spindle positioning requires regulation of MT dynamics, involving depolymerase activities together with cortical and kinetochore-mediated pushing and pulling forces acting on astral MTs and kinetochore fibres. These forces rely on MT motor activities. Cortical pulling forces exerted on astral MTs depend upon dynein/dynactin complexes and are essential in both symmetric and asymmetric cell division. A well-established spindle positioning pathway regulating the cortical targeting of dynein/dynactin involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA (microtubule binding nuclear mitotic apparatus protein) complex. Spindle orientation is also regulated by integrin-mediated cell adhesion and actin retraction fibres that respond to mechanical stress and are influenced by the microenvironment of the dividing cell. Altering the capture of astral MTs or modulating pulling forces affects spindle position, which can impair cell division, differentiation and embryogenesis. In this general scheme, the activity of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial. Recently, the p21-activated kinases (PAKs) emerged as novel important players in mitotic progression. In our recent article, we demonstrated that PAK4 regulates spindle positioning in symmetric cell division. In this commentary, and in light of recent published studies, we discuss how PAK4 could participate in the regulation of mechanisms involved in spindle positioning and orientation. PMID:22960742

  11. p21-activated kinase 4 regulates mitotic spindle positioning and orientation

    PubMed Central

    Bompard, Guillaume; Morin, Nathalie

    2012-01-01

    During mitosis, microtubules (MTs) are massively rearranged into three sets of highly dynamic MTs that are nucleated from the centrosomes to form the mitotic spindle. Tight regulation of spindle positioning in the dividing cell and chromosome alignment at the center of the metaphase spindle are required to ensure perfect chromosome segregation and to position the cytokinetic furrow that will specify the two daughter cells. Spindle positioning requires regulation of MT dynamics, involving depolymerase activities together with cortical and kinetochore-mediated pushing and pulling forces acting on astral MTs and kinetochore fibres. These forces rely on MT motor activities. Cortical pulling forces exerted on astral MTs depend upon dynein/dynactin complexes and are essential in both symmetric and asymmetric cell division. A well-established spindle positioning pathway regulating the cortical targeting of dynein/dynactin involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA (microtubule binding nuclear mitotic apparatus protein) complex.1 Spindle orientation is also regulated by integrin-mediated cell adhesion2 and actin retraction fibres that respond to mechanical stress and are influenced by the microenvironment of the dividing cell.3 Altering the capture of astral MTs or modulating pulling forces affects spindle position, which can impair cell division, differentiation and embryogenesis. In this general scheme, the activity of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial.4 Recently, the p21-activated kinases (PAKs) emerged as novel important players in mitotic progression. In our recent article, we demonstrated that PAK4 regulates spindle positioning in symmetric cell division.5 In this commentary, and in light of recent published studies, we discuss how PAK4 could participate in the regulation of mechanisms involved in spindle positioning and orientation. PMID:22960742

  12. Pharmacological inactivation of CHK1 and WEE1 induces mitotic catastrophe in nasopharyngeal carcinoma cells

    PubMed Central

    Mak, Joyce P.Y.; Man, Wing Yu; Chow, Jeremy P.H.; Ma, Hoi Tang; Poon, Randy Y.C.

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer. As radiotherapy is the primary treatment for NPC, this offers a rationale to investigate if uncoupling the DNA damage responses can sensitize this cancer type. The G2 DNA damage checkpoint is controlled by a cascade of protein kinases: ATM/ATR, which phosphorylates CHK1/CHK2, which in turn phosphorylates WEE1. A number of small molecule inhibitors have been developed against these kinases as potential therapeutic agents. Here we demonstrated that compare to that in immortalized nasopharyngeal epithelial cells, ATR, CHK1, and WEE1 were overexpressed in NPC cell lines. Inhibitors of these kinases were unable to promote extensive mitotic catastrophe in ionizing radiation-treated NPC cells, indicating that they are not very effective radiosensitizer for this cancer. In the absence of prior irradiation, however, mitotic catastrophe could be induced with inhibitors against CHK1 (AZD7762) or WEE1 (MK-1775). NPC cells were more sensitive to WEE1 inactivation than nasopharyngeal epithelial cells. Targeting CHK1 and WEE1 together induced more extensive mitotic catastrophe than the individual components alone. Taken together, our results show that NPC cells depend on CHK1 and WEE1 activity for growth and that inhibitors of these kinases may serve as potential therapeutics for NPC. PMID:26025928

  13. Pharmacological inactivation of CHK1 and WEE1 induces mitotic catastrophe in nasopharyngeal carcinoma cells.

    PubMed

    Mak, Joyce P Y; Man, Wing Yu; Chow, Jeremy P H; Ma, Hoi Tang; Poon, Randy Y C

    2015-08-28

    Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer. As radiotherapy is the primary treatment for NPC, this offers a rationale to investigate if uncoupling the DNA damage responses can sensitize this cancer type. The G2 DNA damage checkpoint is controlled by a cascade of protein kinases: ATM/ATR, which phosphorylates CHK1/CHK2, which in turn phosphorylates WEE1. A number of small molecule inhibitors have been developed against these kinases as potential therapeutic agents. Here we demonstrated that compare to that in immortalized nasopharyngeal epithelial cells, ATR, CHK1, and WEE1 were overexpressed in NPC cell lines. Inhibitors of these kinases were unable to promote extensive mitotic catastrophe in ionizing radiation-treated NPC cells, indicating that they are not very effective radiosensitizer for this cancer. In the absence of prior irradiation, however, mitotic catastrophe could be induced with inhibitors against CHK1 (AZD7762) or WEE1 (MK-1775). NPC cells were more sensitive to WEE1 inactivation than nasopharyngeal epithelial cells. Targeting CHK1 and WEE1 together induced more extensive mitotic catastrophe than the individual components alone. Taken together, our results show that NPC cells depend on CHK1 and WEE1 activity for growth and that inhibitors of these kinases may serve as potential therapeutics for NPC. PMID:26025928

  14. Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells

    PubMed Central

    Vihervaara, Anniina; Sergelius, Christian; Vasara, Jenni; Blom, Malin A. H.; Elsing, Alexandra N.; Roos-Mattjus, Pia; Sistonen, Lea

    2013-01-01

    Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results revealed the molecular mechanisms that maintain cellular homeostasis, including HSF1-driven induction of polyubiquitin genes, as well as HSF1- and HSF2-mediated expression patterns of cochaperones, transcriptional regulators, and signaling molecules. We characterized the genomewide transcriptional response to stress also in mitotic cells where the chromatin is tightly compacted. We found a radically limited binding and transactivating capacity of HSF1, leaving mitotic cells highly susceptible to proteotoxicity. In contrast, HSF2 occupied hundreds of loci in the mitotic cells and localized to the condensed chromatin also in meiosis. These results highlight the importance of the cell cycle phase in transcriptional responses and identify the specific mechanisms for HSF1 and HSF2 in transcriptional orchestration. Moreover, we propose that HSF2 is an epigenetic regulator directing transcription throughout cell cycle progression. PMID:23959860

  15. Mast, a conserved microtubule-associated protein required for bipolar mitotic spindle organization

    PubMed Central

    Lemos, Catarina L.; Sampaio, Paula; Maiato, Helder; Costa, Madalena; Omel’yanchuk, Leonid V.; Liberal, Vasco; Sunkel, Claudio E.

    2000-01-01

    Through mutational analysis in Drosophila, we have identified the gene multiple asters (mast), which encodes a new 165 kDa protein. mast mutant neuroblasts are highly polyploid and show severe mitotic abnormalities including the formation of mono- and multi-polar spindles organized by an irregular number of microtubule-organizing centres of abnormal size and shape. The mast gene product is evolutionarily conserved since homologues were identified from yeast to man, revealing a novel protein family. Antibodies against Mast and analysis of tissue culture cells expressing an enhanced green fluorescent protein–Mast fusion protein show that during mitosis, this protein localizes to centrosomes, the mitotic spindle, centromeres and spindle midzone. Microtubule-binding assays indicate that Mast is a microtubule-associated protein displaying strong affinity for polymerized microtubules. The defects observed in the mutant alleles and the intracellular localization of the protein suggest that Mast plays an essential role in centrosome separation and organization of the bipolar mitotic spindle. PMID:10899121

  16. Mast, a conserved microtubule-associated protein required for bipolar mitotic spindle organization.

    PubMed

    Lemos, C L; Sampaio, P; Maiato, H; Costa, M; Omel'yanchuk, L V; Liberal, V; Sunkel, C E

    2000-07-17

    Through mutational analysis in Drosopjila we have identified the gene multiple asters (mast), which encodes a new 165 kDa protein. mast mutant neuroblasts are highly polyploid and show severe mitotic abnormalities including the formation of mono- and multi-polar spindles organized by an irregular number of microtubule-organizing centres of abnormal size and shape. The mast gene product is evolutionarily conserved since homologues were identified from yeast to man, revealing a novel protein family. Antibodies against Mast and analysis of tissue culture cells expressing an enhanced green fluorescent protein-Mast fusion protein show that during mitosis, this protein localizes to centrosomes, the mitotic spindle, centromeres and spindle midzone. Microtubule-binding assays indicate that Mast is a microtubule-associated protein displaying strong affinity for polymerized microtubules. The defects observed in the mutant alleles and the intracellular localization of the protein suggest that Mast plays an essential role in centrosome separation and organization of the bipolar mitotic spindle. PMID:10899121

  17. Twinning and mitotic crossing-over: some possibilities and their implications.

    PubMed Central

    Ct, G B; Gyftodimou, J

    1991-01-01

    Mitotic crossing-over does occur in man and is much more frequent and important than generally assumed. Its postzygotic occurrence before an embryo differentiates into MZ twins is theoretically predicted to have disrupting effects on genomic imprinting and cis-acting sequences, with consequences ranging from early lethality to MZ twin discordance. Some predictions are at odds with classical views on twinning and include a high discordance rate of MZ twins for some genetic diseases. A review of MZ twin discordance and an attempt at explaining some of the data lead one to hypothesize both the existence of a sex differences in the rate of mitotic crossing-over and the impossibility for crossed X chromosomes to undergo inactivation. The close interrelationship of twinning and midline malformations further suggests a major role of mitotic crossing-over in the induction of the twinning process itself. The model can be tested with molecular methods and provides a new approach for the gene mapping of so-called multifactorial diseases and of rarer disorders with apparently irregular inheritance. PMID:2063864

  18. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

    SciTech Connect

    DiCicco-Bloom, E.; Black, I.B. )

    1988-06-01

    While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating ({sup 3}H)thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of ({sup 3}H)thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain.

  19. Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae

    PubMed Central

    Symington, Lorraine S.; Rothstein, Rodney; Lisby, Michael

    2014-01-01

    Homology-dependent exchange of genetic information between DNA molecules has a profound impact on the maintenance of genome integrity by facilitating error-free DNA repair, replication, and chromosome segregation during cell division as well as programmed cell developmental events. This chapter will focus on homologous mitotic recombination in budding yeast Saccharomyces cerevisiae. However, there is an important link between mitotic and meiotic recombination (covered in the forthcoming chapter by Hunter et al. 2015) and many of the functions are evolutionarily conserved. Here we will discuss several models that have been proposed to explain the mechanism of mitotic recombination, the genes and proteins involved in various pathways, the genetic and physical assays used to discover and study these genes, and the roles of many of these proteins inside the cell. PMID:25381364

  20. Mitotic remodeling of the replicon and chromosome structure.

    PubMed

    Lemaitre, Jean-Marc; Danis, Etienne; Pasero, Philippe; Vassetzky, Yegor; Mchali, Marcel

    2005-12-01

    Animal cloning by nuclear-transfer experiments frequently fails due to the inability of transplanted nuclei to support normal embryonic development. We show here that the formation of mitotic chromosomes in the egg context is crucial for adapting differentiated nuclei for early development. Differentiated erythrocyte nuclei replicate inefficiently in Xenopus eggs but do so as rapidly as sperm nuclei if a prior single mitosis is permitted. This mitotic remodeling involves a topoisomerase II-dependent shortening of chromatin loop domains and an increased recruitment of replication initiation factors onto chromatin, leading to a short interorigin spacing characteristic of early developmental stages. It also occurs within each early embryonic cell cycle and dominantly regulates initiation of DNA replication for the subsequent S phase. These results indicate that mitotic conditioning is crucial to reset the chromatin structure of differentiated adult donor cells for embryonic DNA replication and suggest that it is an important step in nuclear cloning. PMID:16325575

  1. Shaping mitotic chromosomes: From classical concepts to molecular mechanisms

    PubMed Central

    Kschonsak, Marc; Haering, Christian H

    2015-01-01

    How eukaryotic genomes are packaged into compact cylindrical chromosomes in preparation for cell divisions has remained one of the major unsolved questions of cell biology. Novel approaches to study the topology of DNA helices inside the nuclei of intact cells, paired with computational modeling and precise biomechanical measurements of isolated chromosomes, have advanced our understanding of mitotic chromosome architecture. In this Review Essay, we discuss in light of these recent insights the role of chromatin architecture and the functions and possible mechanisms of SMC protein complexes and other molecular machines in the formation of mitotic chromosomes. Based on the information available, we propose a stepwise model of mitotic chromosome condensation that envisions the sequential generation of intra-chromosomal linkages by condensin complexes in the context of cohesin-mediated inter-chromosomal linkages, assisted by topoisomerase II. The described scenario results in rod-shaped metaphase chromosomes ready for their segregation to the cell poles. PMID:25988527

  2. MYC Is a Major Determinant of Mitotic Cell Fate

    PubMed Central

    Topham, Caroline; Tighe, Anthony; Ly, Peter; Bennett, Ailsa; Sloss, Olivia; Nelson, Louisa; Ridgway, Rachel A.; Huels, David; Littler, Samantha; Schandl, Claudia; Sun, Ying; Bechi, Beatrice; Procter, David J.; Sansom, Owen J.; Cleveland, Don W.; Taylor, Stephen S.

    2015-01-01

    Summary Taxol and other antimitotic agents are frontline chemotherapy agents but the mechanisms responsible for patient benefit remain unclear. Following a genome-wide siRNA screen, we identified the oncogenic transcription factor Myc as a taxol sensitizer. Using time-lapse imaging to correlate mitotic behavior with cell fate, we show that Myc sensitizes cells to mitotic blockers and agents that accelerate mitotic progression. Myc achieves this by upregulating a cluster of redundant pro-apoptotic BH3-only proteins and suppressing pro-survival Bcl-xL. Gene expression analysis of breast cancers indicates that taxane responses correlate positively with Myc and negatively with Bcl-xL. Accordingly, pharmacological inhibition of Bcl-xL restores apoptosis in Myc-deficient cells. These results open up opportunities for biomarkers and combination therapies that could enhance traditional and second-generation antimitotic agents. PMID:26175417

  3. Mitotic figure recognition: agreement among pathologists and computerized detector.

    PubMed

    Malon, Christopher; Brachtel, Elena; Cosatto, Eric; Graf, Hans Peter; Kurata, Atsushi; Kuroda, Masahiko; Meyer, John S; Saito, Akira; Wu, Shulin; Yagi, Yukako

    2012-01-01

    Despite the prognostic importance of mitotic count as one of the components of the Bloom-Richardson grade, several studies have found that pathologists' agreement on the mitotic grade is fairly modest. Collecting a set of more than 4,200 candidate mitotic figures, we evaluate pathologists' agreement on individual figures, and train a computerized system for mitosis detection, comparing its performance to the classifications of three pathologists. The system's and the pathologists' classifications are based on evaluation of digital micrographs of hematoxylin and eosin stained breast tissue. On figures where the majority of pathologists agree on a classification, we compare the performance of the trained system to that of the individual pathologists. We find that the level of agreement of the pathologists ranges from slight to moderate, with strong biases, and that the system performs competitively in rating the ground truth set. This study is a step towards automatic mitosis count to accelerate a pathologist's work and improve reproducibility. PMID:21965283

  4. Integrated siRNA design based on surveying of features associated with high RNAi effectiveness

    PubMed Central

    Gong, Wuming; Ren, Yongliang; Xu, Qiqi; Wang, Yejun; Lin, Dong; Zhou, Haiyan; Li, Tongbin

    2006-01-01

    Background Short interfering RNAs have allowed the development of clean and easily regulated methods for disruption of gene expression. However, while these methods continue to grow in popularity, designing effective siRNA experiments can be challenging. The various existing siRNA design guidelines suffer from two problems: they differ considerably from each other, and they produce high levels of false-positive predictions when tested on data of independent origins. Results Using a distinctly large set of siRNA efficacy data assembled from a vast diversity of origins (the siRecords data, containing records of 3,277 siRNA experiments targeting 1,518 genes, derived from 1,417 independent studies), we conducted extensive analyses of all known features that have been implicated in increasing RNAi effectiveness. A number of features having positive impacts on siRNA efficacy were identified. By performing quantitative analyses on cooperative effects among these features, then applying a disjunctive rule merging (DRM) algorithm, we developed a bundle of siRNA design rule sets with the false positive problem well curbed. A comparison with 15 online siRNA design tools indicated that some of the rule sets we developed surpassed all of these design tools commonly used in siRNA design practice in positive predictive values (PPVs). Conclusion The availability of the large and diverse siRNA dataset from siRecords and the approach we describe in this report have allowed the development of highly effective and generally applicable siRNA design rule sets. Together with ever improving RNAi lab techniques, these design rule sets are expected to make siRNAs a more useful tool for molecular genetics, functional genomics, and drug discovery studies. PMID:17129386

  5. Defective in mitotic arrest 1/ring finger 8 is a checkpoint protein that antagonizes the human mitotic exit network.

    PubMed

    Tuttle, Robyn L; Bothos, John; Summers, Matthew K; Luca, Francis C; Halazonetis, Thanos D

    2007-12-01

    A molecular pathway homologous to the S. cerevisiae mitotic exit network (MEN) and S. pombe septation initiation network has recently been described in higher eukaryotes and involves the tumor suppressor kinase LATS1 and its subunit MOB1A. The yeast MEN/septation initiation network pathways are regulated by the ubiquitin ligase defective in mitotic arrest 1 (Dma1p), a checkpoint protein that helps maintain prometaphase arrest when cells are exposed to microtubule poisons. We identified here the RING domain protein ring finger 8 (RNF8) as the human orthologue of the yeast protein Dma1p. Like its yeast counterparts, human DMA1/RNF8 localized at the midbody and its depletion by siRNA compromised mitotic arrest of nocodazole-treated cells in a manner dependent on the MEN. Depletion of MAD2, a spindle checkpoint protein, also compromised mitotic arrest, but in a MEN-independent manner. Thus, two distinct checkpoint pathways maintain mitotic arrest in cells exposed to microtubule poisons. PMID:18171988

  6. Rohitukine inhibits in vitro adipogenesis arresting mitotic clonal expansion and improves dyslipidemia in vivo[S

    PubMed Central

    Varshney, Salil; Shankar, Kripa; Beg, Muheeb; Balaramnavar, Vishal M.; Mishra, Sunil Kumar; Jagdale, Pankaj; Srivastava, Shishir; Chhonker, Yashpal S.; Lakshmi, Vijai; Chaudhari, Bhushan P.; Bhatta, Rabi Shankar; Saxena, Anil Kumar; Gaikwad, Anil Nilkanth

    2014-01-01

    We developed a common feature pharmacophore model using known antiadipogenic compounds (CFPMA). We identified rohitukine, a reported chromone anticancer alkaloid as a potential hit through in silico mapping of the in-house natural product library on CFPMA. Studies were designed to assess the antiadipogenic potential of rohitukine. Rohitukine was isolated from Dysoxylum binacteriferum Hook. to ⬧95% purity. As predicted by CFPMA, rohitukine was indeed found to be an antiadipogenic molecule. Rohitukine inhibited lipid accumulation and adipogenic differentiation in a concentration- and exposure-time-dependent manner in 3T3-L1 and C3H10T1/2 cells. Rohitukine downregulated expression of PPARγ, CCAAT/enhancer binding protein α, adipocyte protein 2 (aP2), FAS, and glucose transporter 4. It also suppressed mRNA expression of LPL, sterol-regulatory element binding protein (SREBP) 1c, FAS, and aP2, the downstream targets of PPARγ. Rohitukine arrests cells in S phase during mitotic clonal expansion. Rohitukine was bioavailable, and 25.7% of orally administered compound reached systemic circulation. We evaluated the effect of rohitukine on dyslipidemia induced by high-fat diet in the hamster model. Rohitukine increased hepatic expression of liver X receptor α and decreased expression of SREBP-2 and associated targets. Rohitukine decreased hepatic and gonadal lipid accumulation and ameliorated dyslipidemia significantly. In summary, our strategy to identify a novel antiadipogenic molecule using CFPMA successfully resulted in identification of rohitukine, which confirmed antiadipogenic activity and also exhibited in vivo antidyslipidemic activity. PMID:24646949

  7. Improved feature extraction from high-resolution remotely sensed imagery using object geometry

    NASA Astrophysics Data System (ADS)

    Momm, H. G.; Gunter, Bryan; Easson, Greg

    2010-04-01

    Information extraction from high spatial resolution imagery is sometimes hampered by the limited number of spectral channels available from these systems. Standard supervised classification algorithms found in commercial software packages may misclassify different features with similar spectral characteristics; leading to a high occurrence of false positives. An additional step in the information extraction process was developed incorporating the concept of object geometry. Objects are defined as a contiguous group of pixels identified as belonging to a single class in the spectral classification. Using results from the spectral classification, a supervised approach was developed using genetic programming to select and mathematically combine feature-specific shape descriptors from a larger set of shape descriptors, to form a new classifier. This investigation focused on extraction of residential housing from QuickBird and IKONOS imagery of the Mississippi Gulf Coast before and immediately after hurricane Katrina. Use of genetic programming significantly reduced false positives caused by asphalt pavement and isolated roofing material scattered throughout the image.

  8. Wavelet feature extraction for reliable discrimination between high explosive and chemical/biological artillery

    NASA Astrophysics Data System (ADS)

    Hohil, Myron E.; Desai, Sachi V.; Bass, Henry E.; Chambers, Jim

    2005-03-01

    Feature extraction methods based on the discrete wavelet transform and multiresolution analysis are used to develop a robust classification algorithm that reliably discriminates between conventional and simulated chemical/biological artillery rounds via acoustic signals produced during detonation. Distinct characteristics arise within the different airburst signatures because high explosive warheads emphasize concussive and shrapnel effects, while chemical/biological warheads are designed to disperse their contents over large areas, therefore employing a slower burning, less intense explosive to mix and spread their contents. The ensuing blast waves are readily characterized by variations in the corresponding peak pressure and rise time of the blast, differences in the ratio of positive pressure amplitude to the negative amplitude, and variations in the overall duration of the resulting waveform. Unique attributes can also be identified that depend upon the properties of the gun tube, projectile speed at the muzzle, and the explosive burn rates of the warhead. In this work, the discrete wavelet transform is used to extract the predominant components of these characteristics from air burst signatures at ranges exceeding 2km. Highly reliable discrimination is achieved with a feedforward neural network classifier trained on a feature space derived from the distribution of wavelet coefficients and higher frequency details found within different levels of the multiresolution decomposition.

  9. Water Extraction in High Resolution Remote Sensing Image Based on Hierarchical Spectrum and Shape Features

    NASA Astrophysics Data System (ADS)

    Li, Bangyu; Zhang, Hui; Xu, Fanjiang

    2014-03-01

    This paper addresses the problem of water extraction from high resolution remote sensing images (including R, G, B, and NIR channels), which draws considerable attention in recent years. Previous work on water extraction mainly faced two difficulties. 1) It is difficult to obtain accurate position of water boundary because of using low resolution images. 2) Like all other image based object classification problems, the phenomena of "different objects same image" or "different images same object" affects the water extraction. Shadow of elevated objects (e.g. buildings, bridges, towers and trees) scattered in the remote sensing image is a typical noise objects for water extraction. In many cases, it is difficult to discriminate between water and shadow in a remote sensing image, especially in the urban region. We propose a water extraction method with two hierarchies: the statistical feature of spectral characteristic based on image segmentation and the shape feature based on shadow removing. In the first hierarchy, the Statistical Region Merging (SRM) algorithm is adopted for image segmentation. The SRM includes two key steps: one is sorting adjacent regions according to a pre-ascertained sort function, and the other one is merging adjacent regions based on a pre-ascertained merging predicate. The sort step is done one time during the whole processing without considering changes caused by merging which may cause imprecise results. Therefore, we modify the SRM with dynamic sort processing, which conducts sorting step repetitively when there is large adjacent region changes after doing merging. To achieve robust segmentation, we apply the merging region with six features (four remote sensing image bands, Normalized Difference Water Index (NDWI), and Normalized Saturation-value Difference Index (NSVDI)). All these features contribute to segment image into region of object. NDWI and NSVDI are discriminate between water and some shadows. In the second hierarchy, we adopt the shape features to remove more shadows. The water polygons are generated by vectorization algorithm after water segmentation, and then some shape parameters (Compact, Critical Point and Symmetry) are considered to remove shadow. To evaluate the performance of the proposed method, we collect several Quick Bird images at 0.61-m resolution which are acquired in May 2009 at GUANGZHOU province of China. The proposed method is compared with four other methods in water extraction, including pixel-based segmentation by NDWI, Mean-sift segmentation by NDWI, and SVM with different channels. Experimental results show that the proposed method can increase extraction accuracy and reduce the influence of shadows.

  10. High-Precision Image Aided Inertial Navigation with Known Features: Observability Analysis and Performance Evaluation

    PubMed Central

    Jiang, Weiping; Wang, Li; Niu, Xiaoji; Zhang, Quan; Zhang, Hui; Tang, Min; Hu, Xiangyun

    2014-01-01

    A high-precision image-aided inertial navigation system (INS) is proposed as an alternative to the carrier-phase-based differential Global Navigation Satellite Systems (CDGNSSs) when satellite-based navigation systems are unavailable. In this paper, the image/INS integrated algorithm is modeled by a tightly-coupled iterative extended Kalman filter (IEKF). Tightly-coupled integration ensures that the integrated system is reliable, even if few known feature points (i.e., less than three) are observed in the images. A new global observability analysis of this tightly-coupled integration is presented to guarantee that the system is observable under the necessary conditions. The analysis conclusions were verified by simulations and field tests. The field tests also indicate that high-precision position (centimeter-level) and attitude (half-degree-level)-integrated solutions can be achieved in a global reference. PMID:25330046

  11. Physiological and genomic features of highly alkaliphilic hydrogen-utilizing Betaproteobacteria from a continental serpentinizing site

    PubMed Central

    Suzuki, Shino; Kuenen, J. Gijs; Schipper, Kira; van der Velde, Suzanne; Ishii, Shun’ichi; Wu, Angela; Sorokin, Dimitry Y.; Tenney, Aaron; Meng, XianYing; Morrill, Penny L.; Kamagata, Yoichi; Muyzer, Gerard; Nealson, Kenneth H.

    2014-01-01

    Serpentinization, or the aqueous alteration of ultramafic rocks, results in challenging environments for life in continental sites due to the combination of extremely high pH, low salinity and lack of obvious electron acceptors and carbon sources. Nevertheless, certain Betaproteobacteria have been frequently observed in such environments. Here we describe physiological and genomic features of three related Betaproteobacterial strains isolated from highly alkaline (pH 11.6) serpentinizing springs at The Cedars, California. All three strains are obligate alkaliphiles with an optimum for growth at pH 11 and are capable of autotrophic growth with hydrogen, calcium carbonate and oxygen. The three strains exhibit differences, however, regarding the utilization of organic carbon and electron acceptors. Their global distribution and physiological, genomic and transcriptomic characteristics indicate that the strains are adapted to the alkaline and calcium-rich environments represented by the terrestrial serpentinizing ecosystems. We propose placing these strains in a new genus ‘Serpentinomonas’. PMID:24845058

  12. High-precision image aided inertial navigation with known features: observability analysis and performance evaluation.

    PubMed

    Jiang, Weiping; Wang, Li; Niu, Xiaoji; Zhang, Quan; Zhang, Hui; Tang, Min; Hu, Xiangyun

    2014-01-01

    A high-precision image-aided inertial navigation system (INS) is proposed as an alternative to the carrier-phase-based differential Global Navigation Satellite Systems (CDGNSSs) when satellite-based navigation systems are unavailable. In this paper, the image/INS integrated algorithm is modeled by a tightly-coupled iterative extended Kalman filter (IEKF). Tightly-coupled integration ensures that the integrated system is reliable, even if few known feature points (i.e., less than three) are observed in the images. A new global observability analysis of this tightly-coupled integration is presented to guarantee that the system is observable under the necessary conditions. The analysis conclusions were verified by simulations and field tests. The field tests also indicate that high-precision position (centimeter-level) and attitude (half-degree-level)-integrated solutions can be achieved in a global reference. PMID:25330046

  13. EEG oscillations entrain their phase to high-level features of speech sound.

    PubMed

    Zoefel, Benedikt; VanRullen, Rufin

    2016-01-01

    Phase entrainment of neural oscillations, the brain's adjustment to rhythmic stimulation, is a central component in recent theories of speech comprehension: the alignment between brain oscillations and speech sound improves speech intelligibility. However, phase entrainment to everyday speech sound could also be explained by oscillations passively following the low-level periodicities (e.g., in sound amplitude and spectral content) of auditory stimulation-and not by an adjustment to the speech rhythm per se. Recently, using novel speech/noise mixture stimuli, we have shown that behavioral performance can entrain to speech sound even when high-level features (including phonetic information) are not accompanied by fluctuations in sound amplitude and spectral content. In the present study, we report that neural phase entrainment might underlie our behavioral findings. We observed phase-locking between electroencephalogram (EEG) and speech sound in response not only to original (unprocessed) speech but also to our constructed "high-level" speech/noise mixture stimuli. Phase entrainment to original speech and speech/noise sound did not differ in the degree of entrainment, but rather in the actual phase difference between EEG signal and sound. Phase entrainment was not abolished when speech/noise stimuli were presented in reverse (which disrupts semantic processing), indicating that acoustic (rather than linguistic) high-level features play a major role in the observed neural entrainment. Our results provide further evidence for phase entrainment as a potential mechanism underlying speech processing and segmentation, and for the involvement of high-level processes in the adjustment to the rhythm of speech. PMID:26341026

  14. Single-walled carbon nanotube-induced mitotic disruption?

    PubMed Central

    Sargent, L.M.; Hubbs, A.F.; Young, S.-H.; Kashon, M.L.; Dinu, C.Z.; Salisbury, J.L.; Benkovic, S.A.; Lowry, D.T.; Murray, A.R.; Kisin, E.R.; Siegrist, K.J.; Battelli, L.; Mastovich, J.; Sturgeon, J.L.; Bunker, K.L.; Shvedova, A.A.; Reynolds, S.H.

    2015-01-01

    Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 ?g/cm2 single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 2472 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 ?g/cm2 SWCNT. Three-dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24 h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes. PMID:22178868

  15. Force and the spindle: Mechanical cues in mitotic spindle orientation

    PubMed Central

    Nestor-Bergmann, Alexander; Goddard, Georgina; Woolner, Sarah

    2014-01-01

    The mechanical environment of a cell has a profound effect on its behaviour, from dictating cell shape to driving the transcription of specific genes. Recent studies have demonstrated that mechanical forces play a key role in orienting the mitotic spindle, and therefore cell division, in both single cells and tissues. Whilst the molecular machinery that mediates the link between external force and the mitotic spindle remains largely unknown, it is becoming increasingly clear that this is a widely used mechanism which could prove vital for coordinating cell division orientation across tissues in a variety of contexts. PMID:25080021

  16. Weighted simultaneous algebraic reconstruction technique for tomosynthesis imaging of objects with high-attenuation features

    SciTech Connect

    Levakhina, Y. M.; Mueller, J.; Buzug, T. M.; Duschka, R. L.; Vogt, F.; Barkhausen, J.

    2013-03-15

    Purpose: This paper introduces a nonlinear weighting scheme into the backprojection operation within the simultaneous algebraic reconstruction technique (SART). It is designed for tomosynthesis imaging of objects with high-attenuation features in order to reduce limited angle artifacts. Methods: The algorithm estimates which projections potentially produce artifacts in a voxel. The contribution of those projections into the updating term is reduced. In order to identify those projections automatically, a four-dimensional backprojected space representation is used. Weighting coefficients are calculated based on a dissimilarity measure, evaluated in this space. For each combination of an angular view direction and a voxel position an individual weighting coefficient for the updating term is calculated. Results: The feasibility of the proposed approach is shown based on reconstructions of the following real three-dimensional tomosynthesis datasets: a mammography quality phantom, an apple with metal needles, a dried finger bone in water, and a human hand. Datasets have been acquired with a Siemens Mammomat Inspiration tomosynthesis device and reconstructed using SART with and without suggested weighting. Out-of-focus artifacts are described using line profiles and measured using standard deviation (STD) in the plane and below the plane which contains artifact-causing features. Artifacts distribution in axial direction is measured using an artifact spread function (ASF). The volumes reconstructed with the weighting scheme demonstrate the reduction of out-of-focus artifacts, lower STD (meaning reduction of artifacts), and narrower ASF compared to nonweighted SART reconstruction. It is achieved successfully for different kinds of structures: point-like structures such as phantom features, long structures such as metal needles, and fine structures such as trabecular bone structures. Conclusions: Results indicate the feasibility of the proposed algorithm to reduce typical tomosynthesis artifacts produced by high-attenuation features. The proposed algorithm assigns weighting coefficients automatically and no segmentation or tissue-classification steps are required. The algorithm can be included into various iterative reconstruction algorithms with an additive updating strategy. It can also be extended to computed tomography case with the complete set of angular data.

  17. Qualitative Features of Cyclones triggering high precipitation events in the Island of Crete, Eastern Mediterranean.

    NASA Astrophysics Data System (ADS)

    Iordanidou, Vasiliki; Koutroulis, Aristeidis; Tsanis, Ioannis; Flocas, Helena

    2013-04-01

    There are many cases where high precipitation or even worse flood events are provoked by cyclonic atmospheric circulation patterns of similar characteristics. In this study, an attempt was made to investigate the features of the cyclones related to these high precipitation events as well as possible correlation of the precipitation characteristics to these cyclones. A statistical analysis of the features of cyclones affecting Crete was performed over a 30-year period (1979-2011). The cyclones identification and characteristics were extracted with the aid of the Melbourne University automatic cyclone finding and tracking scheme (CTS) based on ERA Interim reanalysis datasets. A number of high precipitation events were defined with a threshold criterion based on a dataset of 53 daily precipitation records over the Island of Crete. Track selection was performed using as second criterion the cyclone distance from the study area. The track points of cyclones affecting Crete found to be related to specific rain events where further analyzed in terms of origination, direction and position. Average values of characteristics were also estimated such as the radius, pressure, depth and East/North velocity for the cyclones affecting Crete. The analysis was also extended concerning seasonality (winter, spring, autumn) and locality (eastern, central or western part of the study site) of the events. In all cases cyclones affecting Crete seem to originate mostly Northwest (~55%) and Southwest (~15%) of Crete having a Southeast (~55%) and Northeast (~15%) direction, correspondingly. Also for the majority of the events (>65%) cyclones are mainly attributed to the characteristics of a strong closed system of relatively long duration and track length.

  18. High Resolution Prediction of Calcium-Binding Sites in 3D Protein Structures Using FEATURE

    PubMed Central

    2015-01-01

    Metal-binding proteins are ubiquitous in biological systems ranging from enzymes to cell surface receptors. Among the various biologically active metal ions, calcium plays a large role in regulating cellular and physiological changes. With the increasing number of high-quality crystal structures of proteins associated with their metal ion ligands, many groups have built models to identify Ca2+ sites in proteins, utilizing information such as structure, geometry, or homology to do the inference. We present a FEATURE-based approach in building such a model and show that our model is able to discriminate between nonsites and calcium-binding sites with a very high precision of more than 98%. We demonstrate the high specificity of our model by applying it to test sets constructed from other ions. We also introduce an algorithm to convert high scoring regions into specific site predictions and demonstrate the usage by scanning a test set of 91 calcium-binding protein structures (190 calcium sites). The algorithm has a recall of more than 93% on the test set with predictions found within 3 of the actual sites. PMID:26226489

  19. High-resolution Mapping of Offshore and Onshore Glaciogenic Features in Melville Bay, Northwestern Greenland

    NASA Astrophysics Data System (ADS)

    Freire, F.; Gyllencreutz, R.; Greenwood, S.; Mayer, L. A.; Jakobsson, M.

    2014-12-01

    This study presents results from high resolution mapping in the northwestern part of Greenland's continental shelf, offshore from the Greenland Ice Sheet. The study area is located at about 74o30'N and 58 o40'W where high-resolution seafloor imagery were collected from ~200-500 m water depth. These data were analyzed and compared to existing high-resolution satellite imagery of exposed glacial landforms from the nearby coastal areas. Offshore geophysical mapping equipment consisted of a Kongsberg EM2040 multibeam that was bow-mounted on the sailing vessel Explorer of Sweden together with a Seatex MRU5+ motion sensor and GPS antennas. In addition, a GAVIA autonomous underwater vehicle (AUV) from University of Iceland with installed Geoswath interfometric sonar and Marine Sonic side-scan was used. The data from these systems permitted the production of both 5-m (for the EM2040) and 2-m (for the Geoswath) resolution bathymetric grids for landform analyzes. Sediment characterization analysis was also undertaken using the co-registered backscatter data. The exposed onshore landforms were studied using data from the high-res QuickBird satellite images with a 2-m pixel resolution. Geomorphic analysis of the data shows that past tectonic and glacial scouring processes have shaped the present-day landscape in both the offshore and onshore study areas. The terrain consists of glacially eroded bedrock covered with very thin surficial sediments resembling a 'cnoc-and-lochan' terrain, although the degree of erosion varies spatially, probably as a result of local variations in the rock properties. Different glacially influenced features are identified and described in the study. These features have been used to understand and infer past ice-sheet processes, particularly ice-flow direction and the extent of ice-cover on the continental shelves from previous extreme glaciation events. The backscatter information from the high-resolution interferometric sonar show fine-scale sedimentation patterns which are used to infer bottom water circulation. The study highlights that the use of the high-resolution seafloor mapping systems significantly enhance the quality of geomorphologic landform assessment.

  20. Bayesian Multiscale Analysis of X-Ray Jet Features in High Redshift Quasars

    NASA Astrophysics Data System (ADS)

    McKeough, Kathryn; Siemiginowska, A.; Kashyap, V.; Stein, N.

    2014-01-01

    X-ray emission of powerful quasar jets may be a result of the inverse Compton (IC) process in which the Cosmic Microwave Background (CMB) photons gain energy by interactions with the jet’s relativistic electrons. However, there is no definite evidence that IC/CMB process is responsible for the observed X-ray emission of large scale jets. A step toward understanding the X-ray emission process is to study the Radio and X-ray morphologies of the jet. We implement a sophisticated Bayesian image analysis program, Low-count Image Reconstruction and Analysis (LIRA) (Esch et al. 2004; Conners & van Dyk 2007), to analyze jet features in 11 Chandra images of high redshift quasars (z ~ 2 - 4.8). Out of the 36 regions where knots are visible in the radio jets, nine showed detectable X-ray emission. We measured the ratios of the X-ray and radio luminosities of the detected features and found that they are consistent with the CMB radiation relationship. We derived a range of the bulk lorentz factor (Γ) for detected jet features under the CMB jet emission model. There is no discernible trend of Γ with redshift within the sample. The efficiency of the X-ray emission between the detected jet feature and the corresponding quasar also shows no correlation with redshift. This work is supported in part by the National Science Foundation REU and the Department of Defense ASSURE programs under NSF Grant no.1262851 and by the Smithsonian Institution, and by NASA Contract NAS8-39073 to the Chandra X-ray Center (CXC). This research has made use of data obtained from the Chandra Data Archive and Chandra Source Catalog, and software provided by the CXC in the application packages CIAO, ChIPS, and Sherpa. We thank Teddy Cheung for providing the VLA radio images. Connors, A., & van Dyk, D. A. 2007, Statistical Challenges in Modern Astronomy IV, 371, 101 Esch, D. N., Connors, A., Karovska, M., & van Dyk, D. A. 2004, ApJ, 610, 1213

  1. [Biologic mechanisms of mitotic abnormalities and chromosome number changes in malignant tumors].

    PubMed

    Hegyi, Katalin

    2015-12-01

    The main goal of this work was to study the effect of Aurora kinase expression on cell ploidy and tumorigenesis. Fifty invasive breast cancer, 50 diffuse large B-cell lymphoma and 10 reactive lymph node samples were recruited in the study. Because of the significant correlation with the overall cell proliferation rate, the overexpression of Aurora B could not be stated on the basis of kinase expressing tumor cell fractions alone. The relative expression of Aurora B kinase is better reflected by the AMI index which represents the Aurora B expression in relation to the whole proliferative fraction of the tumor. A higher relative Aurora B expression was associated with higher mitotic activity in B-cell lymphoma. FISH analysis of the AURKB locus did not show any gains or amplifications in the samples analyzed. On the other hand, we have observed the loss of the gene in breast carcinoma and lymphoma samples as well. A strong correlation was shown between AURKB and TP53 copy numbers: AURKB loss was associated with TP53 deletion in all samples. According to our results on breast carcinoma, losses at 17p13.1 and chromosome 17 aneusomy determined by FISH showed a statistically significant correlation. Our study presents the frequent occurrence of chromosome 17 aneusomy in breast carcinoma and B-cell lymphoma samples. Chromosome 17 aneusomy evaluated by FISH correlated with aneuploidy determined by flow cytometry. Direct correlation between kinase expression and ploidy could not be shown. The highest AMI values were seen in B-ALCL samples, and it was associated with high chromosome 17 copy numbers and mitotic activity. The damaged Aurora B kinase function results in regulatory deficiencies in the CPC complex leading to mitotic errors, while p53 deficiency helps malignant cells to survive due to insufficient activation of the intrinsic apoptotic pathways. The upregulation of Aurora kinase B function may cause error in an important mitotic checkpoint, thus resulting in induction of aneuploid cell populations. These parallel effects finally increase the complexity of mitotic abnormalities and generate aneuploid cell populations. PMID:26665199

  2. Aurora-A-Dependent Control of TACC3 Influences the Rate of Mitotic Spindle Assembly

    PubMed Central

    Joseph, Nimesh; Cavazza, Tommaso; Vernos, Isabelle; Pfuhl, Mark; Gergely, Fanni; Bayliss, Richard

    2015-01-01

    The essential mammalian gene TACC3 is frequently mutated and amplified in cancers and its fusion products exhibit oncogenic activity in glioblastomas. TACC3 functions in mitotic spindle assembly and chromosome segregation. In particular, phosphorylation on S558 by the mitotic kinase, Aurora-A, promotes spindle recruitment of TACC3 and triggers the formation of a complex with ch-TOG-clathrin that crosslinks and stabilises kinetochore microtubules. Here we map the Aurora-A-binding interface in TACC3 and show that TACC3 potently activates Aurora-A through a domain centered on F525. Vertebrate cells carrying homozygous F525A mutation in the endogenous TACC3 loci exhibit defects in TACC3 function, namely perturbed localization, reduced phosphorylation and weakened interaction with clathrin. The most striking feature of the F525A cells however is a marked shortening of mitosis, at least in part due to rapid spindle assembly. F525A cells do not exhibit chromosome missegregation, indicating that they undergo fast yet apparently faithful mitosis. By contrast, mutating the phosphorylation site S558 to alanine in TACC3 causes aneuploidy without a significant change in mitotic duration. Our work has therefore defined a regulatory role for the Aurora-A-TACC3 interaction beyond the act of phosphorylation at S558. We propose that the regulatory relationship between Aurora-A and TACC3 enables the transition from the microtubule-polymerase activity of TACC3-ch-TOG to the microtubule-crosslinking activity of TACC3-ch-TOG-clathrin complexes as mitosis progresses. Aurora-A-dependent control of TACC3 could determine the balance between these activities, thereby influencing not only spindle length and stability but also the speed of spindle formation with vital consequences for chromosome alignment and segregation. PMID:26134678

  3. A Small Mission Featuring an Imaging X-ray Polarimeter with High Sensitivity

    NASA Technical Reports Server (NTRS)

    Weisskopf, Martin C.; Baldini, Luca; Bellazini, Ronaldo; Brez, Alessandro; Costa, Enrico; Dissley, Richard; Elsner, Ronald; Fabiani, Sergio; Matt, Giorgio; Minuti, Massimo; Mulieri, Fabio; O'Dell, Steve; Pinchera, Michelle; Ramsey, Brian; Rubini, Alda; Sgro, Carmelo; Soffitta, Paolo; Spandre, Gloria

    2013-01-01

    We present a detailed description of a small mission capable of obtaining high precision and meaningful measurement of the X-ray polarization of a variety of different classes of cosmic X-ray sources. Compared to other ideas that have been suggested this experiment has demonstrated in the laboratory a number of extremely important features relevant to the ultimate selection of such a mission by a funding agency. The most important of these questions are: 1) Have you demonstrated the sensitivity to a polarized beam at the energies of interest (i.e. the energies which represent the majority (not the minority) of detected photons from the X-ray source of interest? 2) Have you demonstrated that the device's sensitivity to an unpolarized beam is really negligible and/or quantified the impact of any systematic effects upon actual measurements? We present our answers to these questions backed up by laboratory measurements and give an overview of the mission.

  4. Nano features of Al/Au ultrasonic bond interface observed by high resolution transmission electron microscopy

    SciTech Connect

    Ji Hongjun; Li Mingyu Kim, Jong-Myung; Kim, Dae-Won; Wang Chunqing

    2008-10-15

    Nano-scale interfacial details of ultrasonic AlSi1 wire wedge bonding to a Au/Ni/Cu pad were investigated using high resolution transmission electron microscopy (HRTEM). The intermetallic phase Au{sub 8}Al{sub 3} formed locally due to diffusion and reaction activated by ultrasound at the Al/Au bond interface. Multilayer sub-interfaces roughly parallel to the wire/pad interface were observed among this phase, and interdiffusional features near the Au pad resembled interference patterns, alternately dark and bright bars. Solid-state diffusion theory cannot be used to explain why such a thick compound formed within milliseconds at room temperature. The major formation of metallurgical bonds was attributed to ultrasonic cyclic vibration.

  5. Spectrally resolved spatiotemporal features of quantum paths in high-order-harmonic generation

    NASA Astrophysics Data System (ADS)

    He, Lixin; Lan, Pengfei; Zhang, Qingbin; Zhai, Chunyang; Wang, Feng; Shi, Wenjing; Lu, Peixiang

    2015-10-01

    We experimentally disentangle the contributions of different quantum paths in high-order-harmonic generation (HHG) from the spectrally and spatially resolved harmonic spectra. By adjusting the laser intensity and focusing position, we simultaneously observe the spectrum splitting, frequency shift, and intensity-dependent modulation of harmonic yields both for the short and long paths. Based on the simulations, we discriminate the physical mechanisms of the intensity-dependent modulation of HHG due to the quantum path interference and macroscopic interference effects. Moreover, it is shown that the atomic dipole phases of different quantum paths are encoded in the frequency shift. In turn, it enables us to retrieve the atomic dipole phases and the temporal chirps of different quantum paths from the measured harmonic spectra. This result gives an informative mapping of spatiotemporal and spectral features of quantum paths in HHG.

  6. Rab11-endosomes contribute to mitotic spindle orientation

    PubMed Central

    Hehnly, Heidi; Doxsey, Stephen

    2014-01-01

    During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 and endosomes in mitosis. Here we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind γ-TuRC components and associate with tubulin in vitro. Rab11-depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively-active Rab11 increases astral microtubules, restores γ-tubulin spindle pole localization and generates robust spindles. This suggests a fundamental role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes co-contribute to these processes through retrograde transport to poles by dynein. PMID:24561039

  7. Rab11 endosomes contribute to mitotic spindle organization and orientation.

    PubMed

    Hehnly, Heidi; Doxsey, Stephen

    2014-03-10

    During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 endosomes in mitosis. Here, we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind γ-TuRC components and associate with tubulin in vitro. Rab11 depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively active Rab11 increases astral microtubules, restores γ-tubulin spindle pole localization, and generates robust spindles. This suggests a role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes cocontribute to these processes through retrograde transport to poles by dynein. PMID:24561039

  8. Occludin Localizes to Centrosomes and Modifies Mitotic Entry*

    PubMed Central

    Runkle, E. Aaron; Sundstrom, Jeffrey M.; Runkle, Kristin B.; Liu, Xuwen; Antonetti, David A.

    2011-01-01

    Proper control of cell cycle progression and barrier function are essential processes to the maintenance of epithelial cell homeostasis. The contribution of tight junction proteins to barrier function is well established, whereas their contribution to cell cycle control is only beginning to be understood. Centrosomes are the principal microtubule organizing centers in eukaryotic cells and centrosome duplication and separation are linked to the cell cycle and mitotic entry. Here we demonstrate that occludin localizes with centrosomes in Madin-Darby canine kidney cells. Immunocytochemistry and biochemical fractionation studies reveal occludin localizes with centrosomes during interphase and occludin Ser-490 phosphorylation at centrosomes increases with mitotic entry. Stable expression of aspartic acid phosphomimetic (S490D) results in centrosomal localization of occludin and increases cell numbers. Furthermore, we provide evidence that occludin regulates centrosome separation and mitotic entry as the nonphosphorylatable alanine mutation (S490A) impedes centrosome separation, delays mitotic entry, and reduces proliferation. Collectively, these studies demonstrate a novel location and function for occludin in centrosome separation and mitosis. PMID:21757728

  9. Adhesion signaling by a novel mitotic substrate of src kinases

    PubMed Central

    Bhatt, Ami S.; Erdjument-Bromage, Hediye; Tempst, Paul; Craik, Charles S.; Moasser, Mark M.

    2011-01-01

    Abstract/Summary Src kinases are activated and relocalize to the cytoplasm during mitosis, but their mitotic function has remained elusive. We describe here a novel mitotic substrate of src kinases. Trask (Transmembrane and Associated with Src Kinases) is a 140kd type I transmembrane glycoprotein unrelated to currently known protein families. Src kinases phosphorylate Trask in vitro and mediate its mitotic hyperphosphorylation in vivo. Trask associates with both yes and src, is localized to the cell membrane during interphase, and undergoes cytoplasmic relocalization during mitosis. Overexpression of Trask leads to cell rounding and a loss of adhesion phenotype. Consistent with a function in cell adhesion, Trask interacts with a number of adhesion and matrix proteins including cadherins, syndecans, and the membrane-type serine protease 1 (MT-SP1), and is proteolytically cleaved by MT-SP1. Trask is unique among cell adhesion molecules in that it is under cell cycle regulation and thus links src kinases with the mitotic regulation of cell adhesion. This suggests a potential pathway by which hyperactive src kinases in tumors can deregulate adhesion signaling and mediate the metastatic phenotype. PMID:16007225

  10. O-GlcNAc Transferase Regulates Mitotic Chromatin Dynamics*

    PubMed Central

    Sakabe, Kaoru; Hart, Gerald W.

    2010-01-01

    Mitosis must faithfully divide the genome such that each progeny inherits the same genetic material. DNA condensation is crucial in ensuring that chromosomes are correctly attached to the mitotic spindle for segregation, preventing DNA breaks or constrictions from the contractile ring. Histones form an octameric complex of basic proteins important in regulating DNA organization and accessibility. Histone post-translational modifications are altered during mitosis, although the roles of these post-translational modifications remain poorly characterized. Here, we report that N-acetylglucosamine (O-GlcNAc) transferase (OGT), the enzyme catalyzing the addition of O-GlcNAc moieties to nuclear and cytoplasmic proteins at serine and threonine residues, regulates some aspects of mitotic chromatin dynamics. OGT protein amounts decrease during M phase. Modest overexpression of OGT alters mitotic histone post-translational modifications at Lys-9, Ser-10, Arg-17, and Lys-27 of histone H3. Overexpression of OGT also prevents mitotic phosphorylation of coactivator-associated arginine methyltransferase 1 (CARM1) and prevents its correct cellular localization during mitosis. Moreover, OGT overexpression results in an increase in abnormal chromosomal bridge formation. Together, these results show that regulating the amount of OGT during mitosis is important in ensuring correct chromosomal segregation during mitosis. PMID:20805223

  11. New insights into the pathology of podocyte loss: mitotic catastrophe.

    PubMed

    Liapis, Helen; Romagnani, Paola; Anders, Hans-Joachim

    2013-11-01

    Podocytes represent an essential component of the kidney's glomerular filtration barrier. They stay attached to the glomerular basement membrane via integrin interactions that support the capillary wall to withstand the pulsating filtration pressure. Podocyte structure is maintained by a dynamic actin cytoskeleton. Terminal differentiation is coupled with permanent exit from the cell cycle and arrest in a postmitotic state. Postmitotic podocytes do not have an infinite life span; in fact, physiologic loss in the urine is documented. Proteinuria and other injuries accelerate podocyte loss or induce death. Mature podocytes are unable to replicate and maintain their actin cytoskeleton simultaneously. By the end of mitosis, cytoskeletal actin forms part of the contractile ring, rendering a round shape to podocytes. Therefore, when podocyte mitosis is attempted, it may lead to aberrant mitosis (ie, mitotic catastrophe). Mitotic catastrophe implies that mitotic podocytes eventually detach or die; this is a previously unrecognized form of podocyte loss and a compensatory mechanism for podocyte hypertrophy that relies on post-G1-phase cell cycle arrest. In contrast, local podocyte progenitors (parietal epithelial cells) exhibit a simple actin cytoskeleton structure and can easily undergo mitosis, supporting podocyte regeneration. In this review we provide an appraisal of the in situ pathology of mitotic catastrophe compared with other proposed types of podocyte death and put experimental and renal biopsy data in a unified perspective. PMID:24007883

  12. MITOTIC ABNORMALITIES IN SEA URCHIN EMBRYOS EXPOSED TO DACTINOMYCIN*

    PubMed Central

    Kiefer, Barry I.; Entelis, Charles F.; Infante, Anthony A.

    1969-01-01

    Dactinomycin at concentrations of 10, 20, 25, and 50 μg/ml causes mitotic abnormalities in sea urchin embryos. Sister chromosome separation is impaired and anaphase bridges are frequently formed. The result is an unequal distribution of the chromosome complement to daughter cells. Possible explanations are discussed. Images PMID:4905991

  13. Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

    PubMed Central

    Trinkle-Mulcahy, Laura; Porter, Michael; Jeyaprakash, A. Arockia

    2015-01-01

    Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression. PMID:26124292

  14. Polyglutamylated Tubulin Binding Protein C1orf96/CSAP Is Involved in Microtubule Stabilization in Mitotic Spindles

    PubMed Central

    Ohta, Shinya; Hamada, Mayako; Sato, Nobuko; Toramoto, Iyo

    2015-01-01

    The centrosome-associated C1orf96/Centriole, Cilia and Spindle-Associated Protein (CSAP) targets polyglutamylated tubulin in mitotic microtubules (MTs). Loss of CSAP causes critical defects in brain development; however, it is unclear how CSAP association with MTs affects mitosis progression. In this study, we explored the molecular mechanisms of the interaction of CSAP with mitotic spindles. Loss of CSAP caused MT instability in mitotic spindles and resulted in mislocalization of Nuclear protein that associates with the Mitotic Apparatus (NuMA), with defective MT dynamics. Thus, CSAP overload in the spindles caused extensive MT stabilization and recruitment of NuMA. Moreover, MT stabilization by CSAP led to high levels of polyglutamylation on MTs. MT depolymerization by cold or nocodazole treatment was inhibited by CSAP binding. Live-cell imaging analysis suggested that CSAP-dependent MT-stabilization led to centrosome-free MT aster formation immediately upon nuclear envelope breakdown without γ-tubulin. We therefore propose that CSAP associates with MTs around centrosomes to stabilize MTs during mitosis, ensuring proper bipolar spindle formation and maintenance. PMID:26562023

  15. Mitotic quiescence, but not unique "stemness," marks the phenotype of bone metastasis-initiating cells in prostate cancer.

    PubMed

    Wang, Ning; Docherty, Freyja; Brown, Hannah K; Reeves, Kim; Fowles, Anne; Lawson, Michelle; Ottewell, Penelope D; Holen, Ingunn; Croucher, Peter I; Eaton, Colby L

    2015-08-01

    This study aimed to identify subpopulations of prostate cancer cells that are responsible for the initiation of bone metastases. Using rapidly dividing human prostate cancer cell lines, we identified mitotically quiescent subpopulations (<1%), which we compared with the rapidly dividing populations for patterns of gene expression and for their ability to migrate to the skeletons of athymic mice. The study used 2-photon microscopy to map the presence/distribution of fluorescently labeled, quiescent cells and luciferase expression to determine the presence of growing bone metastases. We showed that the mitotically quiescent cells were very significantly more tumorigenic in forming bone metastases than fast-growing cells (55 vs. 15%) and had a unique gene expression profile. The quiescent cells were not uniquely stem cell like, with no expression of CD133 but had the same level expression of other putative prostate stem cell markers (CD44 and integrins α2/β1), when compared to the rapidly proliferating population. In addition, mitotic quiescence was associated with very high levels of C-X-C chemokine receptor type 4 (CXCR4) production. Inhibition of CXCR4 activity altered the homing of quiescent tumor cells to bone. Our studies suggest that mitotic dormancy is a unique phenotype that facilitates tumor cell colonization of the skeleton in prostate cancer. PMID:25888599

  16. Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes.

    PubMed

    Platani, Melpomeni; Trinkle-Mulcahy, Laura; Porter, Michael; Jeyaprakash, A Arockia; Earnshaw, William C

    2015-07-01

    Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression. PMID:26124292

  17. Design features and performance of the LAMPF high-intensity beam area

    SciTech Connect

    Agnew, L.; Grisham, D.; Macek, R.J.; Sommer, W.F.; Werbeck, R.D.

    1983-01-01

    LAMPF is a multi-purpose high-intensity meson factory capable of producing a 1 mA beam of 800-MeV protons. The three target cells and the beam stop facilities in the high intensity area have many special design features that are required for operation in the presence of high heat loads and intense radiation fields where accessibility is extremely limited. Reliable targets, beam windows, beam stops, beam transport and diagnostic components, vacuum enclosures, and auxiliary systems have been developed. Sophisticated remote-handling systems are employed for maintenance. Complex protection systems have been developed to guard against damage caused by errant beam. Beam availability approaching 90% has been achieved at currents of 600 to 700 ..mu..A. A new facility for direct proton and neutron radiation effects studies will be installed in 1985. The new facility will provide an integrated spallation neutron flux of up to 5 x 10/sup 17/ m/sup -2/s/sup -1/ and will anable proton irradiation studies in the primary beam.

  18. Cytotoxic effects of cylindrospermopsin in mitotic and non-mitotic Vicia faba cells.

    PubMed

    Garda, Tams; Riba, Miln; Vasas, Gbor; Beyer, Dniel; M-Hamvas, Mrta; Hajdu, Grta; Tndor, Ildik; Mth, Csaba

    2015-02-01

    Cylindrospermopsin (CYN) is a cyanobacterial toxin known as a eukaryotic protein synthesis inhibitor. We aimed to study its effects on growth, stress responses and mitosis of a eukaryotic model, Vicia faba (broad bean). Growth responses depended on exposure time (3 or 6d), cyanotoxin concentration, culture conditions (dark or continuous light) and V. faba cultivar ("Standard" or "ARC Egypt Cross"). At 6d of exposure, CYN had a transient stimulatory effect on root system growth, roots being possibly capable of detoxification. The toxin induced nucleus fragmentation, blebbing and chromosomal breaks indicating double stranded DNA breaks and programmed cell death. Root necrotic tissue was observed at 0.1-20 ?g mL(-1) CYN that probably impeded toxin uptake into vascular tissue. Growth and cell death processes observed were general stress responses. In lateral root tip meristems, lower CYN concentrations (0.01-0.1 ?g mL(-1)) induced the stimulation of mitosis and distinct mitotic phases, irrespective of culture conditions or the cultivar used. Higher cyanotoxin concentrations inhibited mitosis. Short-term exposure of hydroxylurea-synchronized roots to 5 ?g mL(-1) CYN induced delay of mitosis that might have been related to a delay of de novo protein synthesis. CYN induced the formation of double, split and asymmetric preprophase bands (PPBs), in parallel with the alteration of cell division planes, related to the interference of cyanotoxin with protein synthesis, thus it was a plant- and CYN specific alteration. PMID:25016338

  19. Morphological features of Triassic and Late Cretaceous high-latitude radiolarian assemblages (comparative analysis)

    NASA Astrophysics Data System (ADS)

    Bragin, Nikita; Bragina, Liubov

    2010-05-01

    High-latitude radiolarian assemblages of Mesozoic represent particular interest for Boreal-Tethyan correlation of Mesozoic as well as for their paleobiogeography. Radiolarians are the only planktonic protists that present both in low- and high-latitude Mesozoic sections, therefore they have high importance. The aim of this work is to distinguish common and different features of Triassic and Late Cretaceous high-latitude assemblages of Radiolaria during their comparative analysis. We use material from Triassic of Omolon Massif (NE Siberia) (Bragin, Egorov, 2001) and Kotel'nyi Island (Arctic) (Bragin, Bragina, 2009; Bragin, in press) and Late Cretaceous of Western Siberia (Amon, 2000) and Kamchatka Peninsula (Vishnevskaya, 2005; Bragina, 1991). The main trends of radiolarian assemblages from these sections are: quantitative domination of some taxa, presence of characteristic high-latitude taxa that are absent or very rare in low-latitude regions, and relatively low taxonomic diversity with absence of many high taxa and many morphotypes. We made following conclusions after comparative analysis: 1. Triassic assemblages are dominated by morphotypes with bipolar main spines (Pseudostylosphaera and similar forms), and by pylomate forms (Glomeropyle). Genus Glomeropyle has bipolar distribution pattern and it is typically high-latitude taxon. Late Cretaceous assemblages are dominated by forms with bipolar three-bladed main spines (Amphisphaera, Protoxiphotractus, Stylosphaera), by prunoid morphotypes (Amphibrachium, Prunobrachium), discoid spongy forms (Orbiculiforma, Spongodiscus) by three-rayed (Paronaella, Spongotripus), four-rayed (Crucella, Histiastrum) and multirayed stauraxon forms (Pentinastrum, Multastrum). Pylomate forms (Spongopyle) are present in the Late Cretaceous high-latitude assemblages but not so common. 2. Spherical forms with spines that possess apophyses (Kahlerosphaera, Dumitricasphaera) are common for Triassic high-latitude areas, but not present in the Cretaceous assemblages. Spherical forms with hollow, commonly twisted spines (Capnuchosphaera) and with two-bladed spines (Zhamojdasphaera) are present only in the Triassic assemblages. 3. Saturnalids are present both in Triassic and Late Cretaceous high-latitude assemblages but not common. 4. Stauraxon three-rayed forms (like Paronaella) are very rare in the Triassic high-latitude assemblages but very common in the Late Cretaceous ones. Some Late Cretaceous morphotypes of this type have bipolar distribution pattern (Spongotripus). 5. Discoidal forms in the Triassic high-latitude assemblages are represented by Tetraspongodiscus - small forms with 4 radial spines. Cretaceous discoids are highly more diverse and are represented by numerous taxa with variable morphology. 6. Multicyrtoid nassellarians with longitudinal ridges are very rare in the Triassic (Whalenella), but very common in the Late Cretaceous (Pseudodictyomitra, Dictyomitra). Multicyrtoid Stichomitra-type specimens are present both in the Triassic and Cretaceous assemblages. 7. Hat-shaped and highly ornamented Nassellaria are almost absent in the high-latitude Triassic and Late Cretaceous assemblages. 8. During long evolutionary history of Radiolaria typically boreal forms strongly differ, and only morphotypes with bipolar main spines and pylomate forms retain their significance as high-latitude indicators.

  20. Extraction of Airport Features from High Resolution Satellite Imagery for Design and Risk Assessment

    NASA Technical Reports Server (NTRS)

    Robinson, Chris; Qiu, You-Liang; Jensen, John R.; Schill, Steven R.; Floyd, Mike

    2001-01-01

    The LPA Group, consisting of 17 offices located throughout the eastern and central United States is an architectural, engineering and planning firm specializing in the development of Airports, Roads and Bridges. The primary focus of this ARC project is concerned with assisting their aviation specialists who work in the areas of Airport Planning, Airfield Design, Landside Design, Terminal Building Planning and design, and various other construction services. The LPA Group wanted to test the utility of high-resolution commercial satellite imagery for the purpose of extracting airport elevation features in the glide path areas surrounding the Columbia Metropolitan Airport. By incorporating remote sensing techniques into their airport planning process, LPA wanted to investigate whether or not it is possible to save time and money while achieving the equivalent accuracy as traditional planning methods. The Affiliate Research Center (ARC) at the University of South Carolina investigated the use of remotely sensed imagery for the extraction of feature elevations in the glide path zone. A stereo pair of IKONOS panchromatic satellite images, which has a spatial resolution of 1 x 1 m, was used to determine elevations of aviation obstructions such as buildings, trees, towers and fence-lines. A validation dataset was provided by the LPA Group to assess the accuracy of the measurements derived from the IKONOS imagery. The initial goal of this project was to test the utility of IKONOS imagery in feature extraction using ERDAS Stereo Analyst. This goal was never achieved due to problems with ERDAS software support of the IKONOS sensor model and the unavailability of imperative sensor model information from Space Imaging. The obstacles encountered in this project pertaining to ERDAS Stereo Analyst and IKONOS imagery will be reviewed in more detail later in this report. As a result of the technical difficulties with Stereo Analyst, ERDAS OrthoBASE was used to derive aviation obstruction measurements for this project. After collecting ancillary data such as GPS locations, South Carolina Geodetic Survey and Aero Dynamics ground survey points to set up the OrthoBASE Block File, measurements were taken of the various glide path obstructions and compared to the validation dataset. This process yielded the following conclusions: The IKONOS stereo model in conjunction with Imagine OrthoBASE can provide The LPA Group with a fast and cost efficient method for assessing aviation obstructions. Also, by creating our own stereo model we achieved any accuracy better currently available commercial products.

  1. Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line.

    PubMed

    Scholz, Diana; Pltl, Dominik; Genewsky, Andreas; Weng, Matthias; Waldmann, Tanja; Schildknecht, Stefan; Leist, Marcel

    2011-12-01

    We characterized phenotype and function of a fetal human mesencephalic cell line (LUHMES, Lund human mesencephalic) as neuronal model system. Neurodevelopmental profiling of the proliferation stage (d0, day 0) of these conditionally-immortalized cells revealed neuronal features, expressed simultaneously with some early neuroblast and stem cell markers. An optimized 2-step differentiation procedure, triggered by shut-down of the myc transgene, resulted in uniformly post-mitotic neurons within 5 days (d5). This was associated with down-regulation of some precursor markers and further up-regulation of neuronal genes. Neurite network formation involved the outgrowth of 1-2, often > 500 ?m long projections. They showed dynamic growth cone behavior, as evidenced by time-lapse imaging of stably GFP-over-expressing cells. Voltage-dependent sodium channels and spontaneous electrical activity of LUHMES continuously increased from d0 to d11, while levels of synaptic markers reached their maximum on d5. The developmental expression patterns of most genes and of the dopamine uptake- and release-machinery appeared to be intrinsically predetermined, as the differentiation proceeded similarly when external factors such as dibutyryl-cAMP and glial cell derived neurotrophic factor were omitted. Only tyrosine hydroxylase required the continuous presence of cAMP. In conclusion, LUHMES are a robust neuronal model with adaptable phenotype and high value for neurodevelopmental studies, disease modeling and neuropharmacology. PMID:21434924

  2. High surface porosity as the origin of emissivity features in asteroid spectra

    NASA Astrophysics Data System (ADS)

    Vernazza, P.; Delbo, M.; King, P. L.; Izawa, M. R. M.; Olofsson, J.; Lamy, P.; Cipriani, F.; Binzel, R. P.; Marchis, F.; Mern, B.; Tamanai, A.

    2012-11-01

    Emission features in the mid-IR domain (7-25 ?m) are quite ubiquitous among large asteroids and therefore offer the potential to uncover their surface composition. However, when comparing these spectra with the actual laboratory spectra of both minerals and meteorites, they do not necessarily match. Here, and in a companion paper by King et al. (in preparation, 2012), we show that by modifying the sample preparation - typically by suspending meteorite and/or mineral powder (<30 ?m) in IR-transparent KBr (potassium bromide) powder - we are able to reproduce the spectral behavior of those main-belt asteroids with emissivity features. This resulting good match between KBr-diluted meteorite spectra and asteroid spectra suggests an important surface porosity (>90%) for the first millimeter for our asteroid sample. It therefore appears that mid-IR emission spectra of asteroids do not only carry information about their surface composition but they can also help us constraining their surface structure (under-dense versus compact surface structure), as suggested by Emery et al. (Emery, J.P., Cruikshank, D.P., van Cleve, J. [2006]. Icarus 182, 496-512) in the case of the Jupiter Trojans. The large surface porosity inferred from the mid-IR spectra of certain asteroids is also implied by two other independent measurements, namely their thermal inertia and their radar albedo. We further clarified how much compositional information can be retrieved from the mid-IR range by focusing our analysis on a single object, 624 Hektor. We showed that the mid-IR range provides critical constraints (i) on its origin and of that of the red Trojans that we locate in the formation regions of the comets, and (ii) on the primordial composition of the dust present in the outer region (>10 AU) of the Solar Systems protoplanetary disk. Future investigations should focus on finding the mechanism responsible for creating such high surface porosity.

  3. Detailed Hydrographic Feature Extraction from High-Resolution LiDAR Data

    SciTech Connect

    Danny L. Anderson

    2012-05-01

    Detailed hydrographic feature extraction from high-resolution light detection and ranging (LiDAR) data is investigated. Methods for quantitatively evaluating and comparing such extractions are presented, including the use of sinuosity and longitudinal root-mean-square-error (LRMSE). These metrics are then used to quantitatively compare stream networks in two studies. The first study examines the effect of raster cell size on watershed boundaries and stream networks delineated from LiDAR-derived digital elevation models (DEMs). The study confirmed that, with the greatly increased resolution of LiDAR data, smaller cell sizes generally yielded better stream network delineations, based on sinuosity and LRMSE. The second study demonstrates a new method of delineating a stream directly from LiDAR point clouds, without the intermediate step of deriving a DEM. Direct use of LiDAR point clouds could improve efficiency and accuracy of hydrographic feature extractions. The direct delineation method developed herein and termed “mDn”, is an extension of the D8 method that has been used for several decades with gridded raster data. The method divides the region around a starting point into sectors, using the LiDAR data points within each sector to determine an average slope, and selecting the sector with the greatest downward slope to determine the direction of flow. An mDn delineation was compared with a traditional grid-based delineation, using TauDEM, and other readily available, common stream data sets. Although, the TauDEM delineation yielded a sinuosity that more closely matches the reference, the mDn delineation yielded a sinuosity that was higher than either the TauDEM method or the existing published stream delineations. Furthermore, stream delineation using the mDn method yielded the smallest LRMSE.

  4. Retrieval Using Texture Features in High Resolution Multi-spectral Satellite Imagery

    SciTech Connect

    Newsam, S D; Kamath, C

    2004-01-22

    Texture features have long been used in remote sensing applications to represent and retrieve image regions similar to a query region. Various representations of texture have been proposed based on the Fourier power spectrum, spatial co-occurrence, wavelets, Gabor filters, etc. These representations vary in their computational complexity and their suitability for representing different region types. Much of the work done thus far has focused on panchromatic imagery at low to moderate spatial resolutions, such as images from Landsat 1-7 which have a resolution of 15-30 m/pixel, and from SPOT 1-5 which have a resolution of 2.5-20 m/pixel. However, it is not clear which texture representation works best for the new classes of high resolution panchromatic (60-100 cm/pixel) and multi-spectral (4 bands for red, green, blue, and near infra-red at 2.4-4 m/pixel) imagery. It is also not clear how the different spectral bands should be combined. In this paper, we investigate the retrieval performance of several different texture representations using multi-spectral satellite images from IKONOS. A query-by-example framework, along with a manually chosen ground truth dataset, allows different combinations of texture representations and spectral bands to be compared. We focus on the specific problem of retrieving inhabited regions from images of urban and rural scenes. Preliminary results show that (1) the use of all spectral bands improves the retrieval performance, and (2) co-occurrence, wavelet and Gabor texture features perform comparably.

  5. Application Prospects and Microstructural Features in Laser-Induced Rapidly Solidified High-Entropy Alloys

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Pan, Ye; He, Yi-Zhu; Wu, Ji-Li; Yue, T. M.; Guo, Sheng

    2014-10-01

    Recently, high-entropy alloys (HEAs) have attracted much interest in the materials community, as they offer massive opportunities to observe new phenomena, explore new structure, and develop new materials. Particularly, it is attractive to prepare high-performance HEA coatings by laser-induced rapid solidification, which can be formed on the surface of components and parts in a variety of sizes and shapes with a lower cost in comparison with those bulk material fabrication methods. From the technical point of view, laser-induced rapid solidification could hamper the compositional segregation, improve the solubility in solid-solution phases, and lead to the strengthening effect by the grain refinement. This article reviews the recent work on the typical microstructural features and the mechanical and chemical properties in laser-induced rapidly solidified HEAs, and these data are compared with conventional Co- and Ni-based alloy coatings. The article concludes with suggestions for future research and development in HEAs, from considerations of their characteristic properties.

  6. High-Resolution Infrared Space Observatory Spectroscopy of the Unidentified 21 Micron Feature

    NASA Technical Reports Server (NTRS)

    Volk, Kevin; Kwok, Sun; Hrivnak, Bruce

    1999-01-01

    We present Infrared Space Observatory SWS06 mode observations of the 21 micron feature in eight sources, including a first "detection of the feature in IRAS Z02229+6208. The observed feature peak-to-continuum ratios range from 0.13 in IRAS Z02229+6208 to 1.30 in IRAS 07134+1005. The normalized spectra, obtained by the removal of the underlying continua and by scaling the features to the same peak flux value. show that all features have the same intrinsic profile and peak wavelength. There is no evidence for any discrete substructure due to molecular bands in the observed spectra, suggesting that the 21 micron feature is due to either a solid substance or a mixture of many similarly structured large molecules.

  7. Feature selection for neural network based defect classification of ceramic components using high frequency ultrasound.

    PubMed

    Kesharaju, Manasa; Nagarajah, Romesh

    2015-09-01

    The motivation for this research stems from a need for providing a non-destructive testing method capable of detecting and locating any defects and microstructural variations within armour ceramic components before issuing them to the soldiers who rely on them for their survival. The development of an automated ultrasonic inspection based classification system would make possible the checking of each ceramic component and immediately alert the operator about the presence of defects. Generally, in many classification problems a choice of features or dimensionality reduction is significant and simultaneously very difficult, as a substantial computational effort is required to evaluate possible feature subsets. In this research, a combination of artificial neural networks and genetic algorithms are used to optimize the feature subset used in classification of various defects in reaction-sintered silicon carbide ceramic components. Initially wavelet based feature extraction is implemented from the region of interest. An Artificial Neural Network classifier is employed to evaluate the performance of these features. Genetic Algorithm based feature selection is performed. Principal Component Analysis is a popular technique used for feature selection and is compared with the genetic algorithm based technique in terms of classification accuracy and selection of optimal number of features. The experimental results confirm that features identified by Principal Component Analysis lead to improved performance in terms of classification percentage with 96% than Genetic algorithm with 94%. PMID:26081920

  8. Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae

    SciTech Connect

    Mortimer, R.K.; Contopoulou, R.; Schild, D.

    1981-09-01

    Cells of Saccharomyces cerevisiae with mutations in the RAD52 gene have previously been shown to be defective in meiotic and mitotic recombination, in sporulation, and in repair of radiation-induced damage to DNA. In this study we show that diploid cells homozygous for rad52 lose chromosomes at high frequencies and that these frequencies of loss can be increased dramatically by exposure of these cells to x-rays. Genetic analyses of survivors of x-ray treatment demonstrate that chromosome loss events result in the conversion of diploid cells to cells with near haploid chromosome numbers.

  9. High-resolution seismic reflection survey near SPR surface collapse feature at Weeks Island, Louisiana

    SciTech Connect

    Miller, R.D.; Xia, J.; Harding, R.S. Jr.; Steeples, D.W.

    1994-12-31

    Shallow high resolution 2-D and 3-D seismic reflection techniques are assisting in the subsurface delineation of a surface collapse feature (sinkhole) at Weeks Island, Louisiana. Seismic reflection surveys were conducted in March 1994. Data from walkaway noise tests were used to assist selection of field recording parameters. The top of the salt dome is about 180 ft below ground surface at the sinkhole. The water table is an estimated 90 ft below the ground surface. A single coherent reflection was consistently recorded across the entire area of the survey, although stacking velocity and spectral content of the event varied. On the basis of observed travel times and stacking velocities, the coherent reflection event appears to originate above the top of the salt, possibly at or near the water table. Identification of this reflector will be made form borehole investigations currently planned for the sinkhole site. A depression or time sag in this reflection event is clearly evident in both the 2-D and 3-D seismic data in the immediate vicinity of the sinkhole. The time sag appears to be related to the subsurface structure of the reflector and not to near surface topography or velocity effects. Elsewhere in the survey area, observed changes in reflection travel times and wavelet character appear to be related to subsurface geologic structure. These seismic observations may assist in predicting where future sinkholes will develop after they have been tied to borehole data collected at the site.

  10. Etching of Silicon in HBr Plasmas for High Aspect Ratio Features

    NASA Technical Reports Server (NTRS)

    Hwang, Helen H.; Meyyappan, M.; Mathad, G. S.; Ranade, R.

    2002-01-01

    Etching in semiconductor processing typically involves using halides because of the relatively fast rates. Bromine containing plasmas can generate high aspect ratio trenches, desirable for DRAM and MEMS applications, with relatively straight sidewalk We present scanning electron microscope images for silicon-etched trenches in a HBr plasma. Using a feature profile simulation, we show that the removal yield parameter, or number of neutrals removed per incident ion due to all processes (sputtering, spontaneous desorption, etc.), dictates the profile shape. We find that the profile becomes pinched off when the removal yield is a constant, with a maximum aspect ratio (AR) of about 5 to 1 (depth to height). When the removal yield decreases with increasing ion angle, the etch rate increases at the comers and the trench bottom broadens. The profiles have ARs of over 9:1 for yields that vary with ion angle. To match the experimentally observed etched time of 250 s for an AR of 9:1 with a trench width of 0.135 microns, we find that the neutral flux must be 3.336 x 10(exp 17)sq cm/s.

  11. High borides: determining the features and details of lattice dynamics from neutron spectroscopy

    NASA Astrophysics Data System (ADS)

    Alekseev, P. A.

    2015-04-01

    We review wide-ranging research that combines inelastic neutron scattering spectroscopy with phenomenological and ab initio calculations to study the lattice dynamics and specifics of the electron-phonon interaction in three-dimensional boron cluster network systems M B_6 and M B12 ( M= {La}, {Sm}, and {Yb}, {Lu}, {Zr}). A close similarity is found between the atomic vibration spectra of these systems, which is fundamentally due to a strong hierarchy of interatomic interaction in these systems and which manifests itself both in the shape of the low-energy phonon dispersion and in the position of the high-energy edge of the spectrum. Manifestations of strong electron-phonon interactions in the lattice vibration spectra of borides are studied in detail and their relation to the nature and features of the valence-unstable state of rare-earth ions is examined. Resonance nonadiabaticity and magnetovibration interaction effects in spin- and valence-fluctuating systems are given special attention.

  12. Some features of bulk melt-textured high-temperature superconductors subjected to alternating magnetic fields

    NASA Astrophysics Data System (ADS)

    Vanderbemden, P.; Molenberg, I.; Simeonova, P.; Lovchinov, V.

    2014-12-01

    Monolithic, large grain, (RE)Ba2Cu3O7 high-temperature superconductors (where RE denotes a rare-earth ion) are known to be able to trap fields in excess of several teslas and represent thus an extremely promising competing technology for permanent magnet in several applications, e.g. in motors and generators. In any rotating machine, however, the superconducting permanent magnet is subjected to variable (transient, or alternating) parasitic magnetic fields. These magnetic fields interact with the superconductor, which yields a reduction of the remnant magnetization. In the present work we quantify these effects by analysing selected experimental data on bulk melt-textured superconductors subjected to AC fields. Our results indicate that the non-uniformity of superconducting properties in rather large samples might lead to unusual features and need to be taken into account to analyse the experimental data. We also investigate the evolution of the DC remnant magnetization of the bulk sample when it is subjected to a large number of AC magnetic field cycles, and investigate the experimental errors that result from a misorientation of the sample or a mispositioning of the Hall probe. The time-dependence of the remnant magnetization over 100000 cycles of the AC field is shown to display distinct regimes which all differ strongly from the usual decay due to magnetic relaxation.

  13. The Salience of Lower-Order Features in Highly Self-Similar Wallpaper Groups.

    PubMed

    Vedak, Shivam; Gilmore, Rick; Kohler, Peter; Liu, Yanxi; Norcia, Anthony

    2015-09-01

    Symmetric visual patterns arise frequently in natural images and human cultural artifacts. All 2-D symmetric patterns that tile the plane represent one of 17 "wallpapers" -- combinations of the fundamental symmetries of rotation, translation, glide reflection and reflection. Most research on human perception has focused on two-fold reflection. Here we examine how human observers classify patterns with varying combinations of the fundamental symmetries. Clarke et al. (2011) found that five of the seventeen wallpaper groups (P1, P3M1, P31M, P6, and P6M) had a high degree of self-similarity. We presented adult participants (n=11) with twenty spatial-frequency-normalized exemplars from each of the five highly self-similar wallpaper groups. Each exemplar was generated from a seed region containing random grayscale noise, which was then replicated, rotated, reflected, and translated according to the pattern of regularity reflected in each wallpaper group. Observers were instructed to sort the exemplars into as many subsets as they wished based on any criteria they saw appropriate. We used the Jaccard index to measure the degree to which observers sorted exemplars from the wallpaper patterns into consistent categories. Observers found consistent patterns of self-similarity between the wallpaper groups, p< .001. P1 exemplars were judged to be more self-similar than than the other groups, p< .001, and P6M exemplars were judged to be more self-similar than P6, p< .001. The findings suggest that mirror and translational symmetry influence unconstrained observer judgments about pattern regularity. Visual inspection of the subsets generated by observers suggested that the presence of salient secondary features (i.e. emergent global geometric structures such as striations, grid patterns, and characteristic shapes) influences the detection of self-similarity in wallpaper patterns. The results contribute to an emerging understanding of how group theory may shed light on human and machine pattern detection. Meeting abstract presented at VSS 2015. PMID:26326527

  14. Special features of a substorm during high solar wind dynamic pressure

    SciTech Connect

    Lui, A.T.Y.; Ohtani, S.; Newell, P.T.

    1995-10-01

    A substorm on July 24, 1986, exhibiting a rather unusual auroral morphology is analyzed with data from spacecraft (Viking; DMSP F6 and F7; GOES 5 and 6; three LANL geosynchronous satellites; CCE; and IMP 8). This substorm occurred during high solar wind dynamic pressure (>5 nPa). Several notable features for this substorm are: (1) the substorm onset activity was preceded by prominent auroral activations in the morning sector with spatial separations between adjacent bright regions ranging from {approximately}160 to 640 km, and their intensity was modulated at {approximately}3.2-min intervals; (2) the initial substorm activity was concentrated in the morning sector, followed by a sudden activation in the dusk sector, leaving the midnight sector relatively undisturbed, in sharp contrast to the traditional substorm development; (3) while a substorm injection was observed at a geocentric distance of {approximately}8.4 R{sub E} by CCE in association with the substorm onset, particle injections (detectable with three LANL geosynchronous satellites) and dipolarization signatures (detectable by the two GOES satellites) were not observed until subsequent intensifications; (4) timing subsequent substorm intensifications from injections at the geosynchronous altitude differed from timing intensifications based on Viking auroral images by as much as {approximately}3 min; (5) the polar cap boundary was at a significantly higher latitude than the poleward boundary delineated by detectable auroral luminosity in the auroral oval. Detailed timing analysis suggests the substorm onset to be associated with southward interplanetary magnetic field (IMF), possibly with the crossing of an IMF sector boundary (interplanetary current sheet). The dimming of auroral luminosity in the midnight region was associated with a sudden northward turning of the IMF during high solar wind dynamic pressure condition. 36 refs., 14 figs.

  15. The Endocrine Dyscrasia that Accompanies Menopause and Andropause Induces Aberrant Cell Cycle Signaling that Triggers Cell Cycle Reentry of Post-mitotic Neurons, Neurodysfunction, Neurodegeneration and Cognitive Disease

    PubMed Central

    Atwood, Craig S.; Bowen, Richard L.

    2016-01-01

    Sex hormones are the physiological factors that regulate neurogenesis during embryogenesis and continuing through adulthood. These hormones support the formation of brain structures such as dendritic spines, axons and synapses required for the capture of information (memories). Intriguingly, a recent animal study has demonstrated that induction of neurogenesis results in the loss of previously encoded memories in animals (e.g. infantile amnesia). In this connection, much evidence now indicates that Alzheimer’s disease (AD) also involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Since sex hormones control when and how neurons proliferate and differentiate, the endocrine dyscrasia that accompanies menopause and andropause is a key signaling event that impacts neurogenesis and the acquisition, processing, storage and recall of memories. Here we review the biochemical, epidemiological and clinical evidence that alterations in endocrine signaling with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle with neurite retraction that leads to neuron dysfunction and death. When the reproductive axis is in balance, luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the ratio of LH:sex steroids as driving aberrant mitotic events mediated by the upregulation of tumor necrosis factor, amyloid-β precursor protein processing towards the production of mitogenic Aβ, and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive studies also demonstrate the negative consequences of a high LH:sex steroid ratio on human cognitive performance. Prospective epidemiological and clinical evidence in humans supports lowering the ratio of circulating gonadotropins-GnRH to sex steroids in reducing the incidence of AD and halting cognitive decline. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson’s disease. PMID:26188949

  16. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor

    PubMed Central

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Abstract Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis. Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center. The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs. The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  17. Architectural epigenetics: mitotic retention of mammalian transcriptional regulatory information.

    PubMed

    Zaidi, Sayyed K; Young, Daniel W; Montecino, Martin; Lian, Jane B; Stein, Janet L; van Wijnen, Andre J; Stein, Gary S

    2010-10-01

    Epigenetic regulatory information must be retained during mammalian cell division to sustain phenotype-specific and physiologically responsive gene expression in the progeny cells. Histone modifications, DNA methylation, and RNA-mediated silencing are well-defined epigenetic mechanisms that control the cellular phenotype by regulating gene expression. Recent results suggest that the mitotic retention of nuclease hypersensitivity, selective histone marks, as well as the lineage-specific transcription factor occupancy of promoter elements contribute to the epigenetic control of sustained cellular identity in progeny cells. We propose that these mitotic epigenetic signatures collectively constitute architectural epigenetics, a novel and essential mechanism that conveys regulatory information to sustain the control of phenotype and proliferation in progeny cells by bookmarking genes for activation or suppression. PMID:20696837

  18. A molecular mechanism of mitotic centrosome assembly in Drosophila.

    PubMed

    Conduit, Paul T; Richens, Jennifer H; Wainman, Alan; Holder, James; Vicente, Catarina C; Pratt, Metta B; Dix, Carly I; Novak, Zsofia A; Dobbie, Ian M; Schermelleh, Lothar; Raff, Jordan W

    2014-01-01

    Centrosomes comprise a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, but it is unclear how this occurs. In this study, we show that the centriole protein Asl initiates the recruitment of DSpd-2 and Cnn to mother centrioles; both proteins then assemble into co-dependent scaffold-like structures that spread outwards from the mother centriole and recruit most, if not all, other PCM components. In the absence of either DSpd-2 or Cnn, mitotic PCM assembly is diminished; in the absence of both proteins, it appears to be abolished. We show that DSpd-2 helps incorporate Cnn into the PCM and that Cnn then helps maintain DSpd-2 within the PCM, creating a positive feedback loop that promotes robust PCM expansion around the mother centriole during mitosis. These observations suggest a surprisingly simple mechanism of mitotic PCM assembly in flies. PMID:25149451

  19. Control of the mitotic cleavage plane by local epithelial topology

    PubMed Central

    Gibson, William T.; Veldhuis, James H.; Rubinstein, Boris; Cartwright, Heather N.; Perrimon, Norbert; Brodland, G. Wayne; Nagpal, Radhika; Gibson, Matthew C.

    2012-01-01

    SUMMARY For nearly 150 years, it has been recognized that cell shape strongly influences the orientation of the mitotic cleavage plane (e.g. Hofmeister, 1863). However, we still understand little about the complex interplay between cell shape and cleavage plane orientation in epithelia, where polygonal cell geometries emerge from multiple factors, including cell packing, cell growth, and cell division itself. Here, using mechanical simulations, we show that the polygonal shapes of individual cells can systematically bias the long axis orientations of their adjacent mitotic neighbors. Strikingly, analysis of both animal epithelia and plant epidermis confirm a robust and nearly identical correlation between local cell topology and cleavage plane orientation in vivo. Using simple mathematics, we show that this effect derives from fundamental packing constraints. Our results suggest that local epithelial topology is a key determinant of cleavage plane orientation, and that cleavage plane bias may be a widespread property of polygonal cell sheets in plants and animals. PMID:21295702

  20. The Mitotic Exit Network: new turns on old pathways.

    PubMed

    Hotz, Manuel; Barral, Yves

    2014-03-01

    In budding yeast, the Mitotic Exit Network (MEN) is a signaling pathway known to drive cells out of mitosis and promote the faithful division of cells. The MEN triggers inactivation of cyclin-dependent kinase (Cdk1), the master regulator of mitosis, and the onset of cytokinesis after segregation of the daughter nuclei. The current model of the MEN suggests that MEN activity is restricted to late anaphase and coordinated with proper alignment of the spindle pole bodies (SPBs) with the division axis. However, recent evidence suggests that MEN activity may function earlier in mitosis, prompting re-evaluation of the current model. Here we attempt to integrate this recent progress into the current view of mitotic exit. PMID:24594661

  1. Molecular pathways regulating mitotic spindle orientation in animal cells

    PubMed Central

    Lu, Michelle S.; Johnston, Christopher A.

    2013-01-01

    Orientation of the cell division axis is essential for the correct development and maintenance of tissue morphology, both for symmetric cell divisions and for the asymmetric distribution of fate determinants during, for example, stem cell divisions. Oriented cell division depends on the positioning of the mitotic spindle relative to an axis of polarity. Recent studies have illuminated an expanding list of spindle orientation regulators, and a molecular model for how cells couple cortical polarity with spindle positioning has begun to emerge. Here, we review both the well-established spindle orientation pathways and recently identified regulators, focusing on how communication between the cell cortex and the spindle is achieved, to provide a contemporary view of how positioning of the mitotic spindle occurs. PMID:23571210

  2. Brownian dynamics simulation of fission yeast mitotic spindle formation

    NASA Astrophysics Data System (ADS)

    Edelmaier, Christopher

    2014-03-01

    The mitotic spindle segregates chromosomes during mitosis. The dynamics that establish bipolar spindle formation are not well understood. We have developed a computational model of fission-yeast mitotic spindle formation using Brownian dynamics and kinetic Monte Carlo methods. Our model includes rigid, dynamic microtubules, a spherical nuclear envelope, spindle pole bodies anchored in the nuclear envelope, and crosslinkers and crosslinking motor proteins. Crosslinkers and crosslinking motor proteins attach and detach in a grand canonical ensemble, and exert forces and torques on the attached microtubules. We have modeled increased affinity for crosslinking motor attachment to antiparallel microtubule pairs, and stabilization of microtubules in the interpolar bundle. We study parameters controlling the stability of the interpolar bundle and assembly of a bipolar spindle from initially adjacent spindle-pole bodies.

  3. Mitotic activity in dorsal epidermis of Rana pipiens.

    NASA Technical Reports Server (NTRS)

    Garcia-Arce, H.; Mizell, S.

    1972-01-01

    Study of statistically significant rhythms of mitotic division in dorsal epidermis of frogs, Rana pipiens, exposed to a 12:12 light:dark environment for 14 days. The results include the findings that (1) male animals have a primary period of 22 hr in summer and 18 hr in winter, (2) female animals have an 18 hr period, and (3) parapinealectomy and blinding abolish the rhythm.

  4. Microdevice having interior cavity with high aspect ratio surface features and associated methods of manufacture and use

    DOEpatents

    Morales, Alfredo M. (Pleasanton, CA)

    2002-01-01

    A microdevice having interior cavity with high aspect ratio features and ultrasmooth surfaces, and associated method of manufacture and use is described. An LIGA-produced shaped bit is used to contour polish the surface of a sacrificial mandrel. The contoured sacrificial mandrel is subsequently coated with a structural material and the mandrel removed to produce microdevices having micrometer-sized surface features and sub-micrometer RMS surface roughness.

  5. A hybrid feature extraction selection approach for high-dimensional non-Gaussian data clustering.

    PubMed

    Boutemedjet, Sabri; Bouguila, Nizar; Ziou, Djemel

    2009-08-01

    This paper presents an unsupervised approach for feature selection and extraction in mixtures of generalized Dirichlet (GD) distributions. Our method defines a new mixture model that is able to extract independent and non-Gaussian features without loss of accuracy. The proposed model is learned using the Expectation-Maximization algorithm by minimizing the message length of the data set. Experimental results show the merits of the proposed methodology in the categorization of object images. PMID:19542577

  6. Mitotic Exit in the Absence of Separase Activity

    PubMed Central

    Lu, Ying

    2009-01-01

    In budding yeast, three interdigitated pathways regulate mitotic exit (ME): mitotic cyclincyclin-dependent kinase (Cdk) inactivation; the Cdc14 early anaphase release (FEAR) network, including a nonproteolytic function of separase (Esp1); and the mitotic exit network (MEN) driven by interaction between the spindle pole body and the bud cortex. Here, we evaluate the contributions of these pathways to ME kinetics. Reducing Cdk activity is critical for ME, and the MEN contributes strongly to ME efficiency. Esp1 contributes to ME kinetics mainly through cohesin cleavage: the Esp1 requirement can be largely bypassed if cells are provided Esp1-independent means of separating sister chromatids. In the absence of Esp1 activity, we observed only a minor ME delay consistent with a FEAR defect. Esp1 overexpression drives ME in Cdc20-depleted cells arrested in metaphase. We have found that this activity of overexpressed Esp1 depended on spindle integrity and the MEN. We defined the first quantitative measure for Cdc14 release based on colocalization with the Net1 nucleolar anchor. This measure indicates efficient Cdc14 release upon MEN activation; release driven by Esp1 in the absence of microtubules was inefficient and incapable of driving ME. We also found a novel role for the MEN: activating Cdc14 nuclear export, even in the absence of Net1. PMID:19144818

  7. Pulling it together: The mitotic function of TACC3.

    PubMed

    Hood, Fiona E; Royle, Stephen J

    2011-05-01

    Transforming acidic coiled coil 3 (TACC3) is a non-motor microtubule-associated protein (MAP) that is important for mitotic spindle stability and organization. The exact mechanism by which TACC3 acts at microtubules to stabilize the spindle has been unclear. However, several recent studies identified that the TACC3 complex at microtubules contains clathrin in addition to its previously identified binding partner, colonic and hepatic tumor overexpressed gene (ch-TOG). In this complex, phosphorylated TACC3 interacts directly with both ch-TOG and clathrin heavy chain, promoting accumulation of all complex members at the mitotic spindle. This complex stabilizes kinetochore fibers within the spindle by forming cross-bridges that link adjacent microtubules in these bundles. So, TACC3 is an adaptor that recruits ch-TOG and clathrin to mitotic microtubules, in an Aurora A kinase-regulated manner. In this mini-review we will describe the recent advances in the understanding of TACC 3 function and present a model that pulls together these new data with previous observations. PMID:21922039

  8. The overlooked greatwall: a new perspective on mitotic control

    PubMed Central

    Glover, David M.

    2012-01-01

    The role of the dual specificity protein phosphatase, Cdc25, in activating the cyclin-dependent kinase-cyclin B complex (Cdk1-CycB) by overcoming the inhibitory Wee1 kinase is a long-established principle for mitotic entry. Recently, however, evidence has emerged of a regulatory network that facilitates Cdk1-CycB activity by inhibiting the form of protein phosphatase 2A having a B55 regulatory subunit (PP2A-B55). Here, I review the genetic and biochemical evidence for Greatwall kinase and its substrate Endosulphine as the key components of this previously obscure regulatory network. Not only is the inhibition of PP2A-B55 by phospho-endosulphine required to prevent dephosphorylation of Cdk1-CycB substrates until mitotic exit, but it is also required to promote Cdc25 activity and inhibit Wee1 at mitotic entry. I discuss how these alternating states of preferential PP2A-B55 or Cdk1-CycB activity can have an impact upon the regulation of Polo kinase and its ability to bind different partner proteins as mitosis progresses. PMID:22754657

  9. A Protein Interaction Map of the Mitotic Spindle

    PubMed Central

    Wong, Jonathan; Nakajima, Yuko; Westermann, Stefan; Shang, Ching; Kang, Jung-seog; Goodner, Crystal; Houshmand, Pantea; Fields, Stanley; Chan, Clarence S.M.; Drubin, David; Hazbun, Tony

    2007-01-01

    The mitotic spindle consists of a complex network of proteins that segregates chromosomes in eukaryotes. To strengthen our understanding of the molecular composition, organization, and regulation of the mitotic spindle, we performed a system-wide two-hybrid screen on 94 proteins implicated in spindle function in Saccharomyces cerevisiae. We report 604 predominantly novel interactions that were detected in multiple screens, involving 303 distinct prey proteins. We uncovered a pattern of extensive interactions between spindle proteins reflecting the intricate organization of the spindle. Furthermore, we observed novel connections between kinetochore complexes and chromatin-modifying proteins and used phosphorylation site mutants of NDC80/TID3 to gain insights into possible phospho-regulation mechanisms. We also present analyses of She1p, a novel spindle protein that interacts with the Dam1 kinetochore/spindle complex. The wealth of protein interactions presented here highlights the extent to which mitotic spindle protein functions and regulation are integrated with each other and with other cellular activities. PMID:17634282

  10. Role of senescence and mitotic catastrophe in cancer therapy

    PubMed Central

    2010-01-01

    Senescence and mitotic catastrophe (MC) are two distinct crucial non-apoptotic mechanisms, often triggered in cancer cells and tissues in response to anti-cancer drugs. Chemotherapeuticals and myriad other factors induce cell eradication via these routes. While senescence drives the cells to a state of quiescence, MC drives the cells towards death during the course of mitosis. The senescent phenotype distinguishes tumor cells that survived drug exposure but lost the ability to form colonies from those that recover and proliferate after treatment. Although senescent cells do not proliferate, they are metabolically active and may secrete proteins with potential tumor-promoting activities. The other anti-proliferative response of tumor cells is MC that is a form of cell death that results from abnormal mitosis and leads to the formation of interphase cells with multiple micronuclei. Different classes of cytotoxic agents induce MC, but the pathways of abnormal mitosis differ depending on the nature of the inducer and the status of cell-cycle checkpoints. In this review, we compare the two pathways and mention that they are activated to curb the growth of tumors. Altogether, we have highlighted the possibilities of the use of senescence targeting drugs, mitotic kinases and anti-mitotic agents in fabricating novel strategies in cancer control. PMID:20205872

  11. Distance-Independence of Mitotic Intrachromosomal Recombination in Saccharomyces Cerevisiae

    PubMed Central

    Yuan, L. W.; Keil, R. L.

    1990-01-01

    Many genetic studies have shown that the frequency of homologous recombination depends largely on the distance in which recombination can occur. We have studied the effect of varying the length of duplicated sequences on the frequency of mitotic intrachromosomal recombination in Saccharomyces cerevisiae. We find that the frequency of recombination resulting in the loss of one of the repeats and the intervening sequences reaches a plateau when the repeats are short. In addition, the frequency of recombination to correct a point mutation contained in one of these repeats is not proportional to the size of the duplication but rather depends dramatically on the location of the mutation within the repeated sequences. However, the frequency of mitotic interchromosomal reciprocal recombination is dependent on the distance separating the markers. The difference in the response of intrachromosomal and interchromosomal mitotic recombination to increasing lengths of homology may indicate there are different rate-limiting steps for recombination in these two cases. These findings have important implications for the maintenance and evolution of duplicated sequences. PMID:2407612

  12. Mitotic Figure Recognition: Agreement among Pathologists and Computerized Detector

    PubMed Central

    Malon, Christopher; Brachtel, Elena; Cosatto, Eric; Graf, Hans Peter; Kurata, Atsushi; Kuroda, Masahiko; Meyer, John S.; Saito, Akira; Wu, Shulin; Yagi, Yukako

    2012-01-01

    Despite the prognostic importance of mitotic count as one of the components of the Bloom Richardson grade [3], several studies ([2, 9, 10]) have found that pathologists agreement on the mitotic grade is fairly modest. Collecting a set of more than 4,200 candidate mitotic figures, we evaluate pathologists' agreement on individual figures, and train a computerized system for mitosis detection, comparing its performance to the classifications of three pathologists. The systems and the pathologists classifications are based on evaluation of digital micrographs of hematoxylin and eosin stained breast tissue. On figures where the majority of pathologists agree on a classification, we compare the performance of the trained system to that of the individual pathologists. We find that the level of agreement of the pathologists ranges from slight to moderate, with strong biases, and that the system performs competitively in rating the ground truth set. This study is a step towards automatic mitosis count to accelerate a pathologist's work and improve reproducibility. PMID:21965283

  13. The Plk1-dependent Phosphoproteome of the Early Mitotic Spindle*

    PubMed Central

    Santamaria, Anna; Wang, Bin; Elowe, Sabine; Malik, Rainer; Zhang, Feng; Bauer, Manuel; Schmidt, Alexander; Silljé, Herman H. W.; Körner, Roman; Nigg, Erich A.

    2011-01-01

    Polo-like kinases regulate many aspects of mitotic and meiotic progression from yeast to man. In early mitosis, mammalian Polo-like kinase 1 (Plk1) controls centrosome maturation, spindle assembly, and microtubule attachment to kinetochores. However, despite the essential and diverse functions of Plk1, the full range of Plk1 substrates remains to be explored. To investigate the Plk1-dependent phosphoproteome of the human mitotic spindle, we combined stable isotope labeling by amino acids in cell culture with Plk1 inactivation or depletion followed by spindle isolation and mass spectrometry. Our study identified 358 unique Plk1-dependent phosphorylation sites on spindle proteins, including novel substrates, illustrating the complexity of the Plk1-dependent signaling network. Over 100 sites were validated by in vitro phosphorylation of peptide arrays, resulting in a broadening of the Plk1 consensus motif. Collectively, our data provide a rich source of information on Plk1-dependent phosphorylation, Plk1 docking to substrates, the influence of phosphorylation on protein localization, and the functional interaction between Plk1 and Aurora A on the early mitotic spindle. PMID:20860994

  14. Unconventional Functions of Mitotic Kinases in Kidney Tumorigenesis

    PubMed Central

    Hascoet, Pauline; Chesnel, Franck; Le Goff, Cathy; Le Goff, Xavier; Arlot-Bonnemains, Yannick

    2015-01-01

    Human tumors exhibit a variety of genetic alterations, including point mutations, translocations, gene amplifications and deletions, as well as aneuploid chromosome numbers. For carcinomas, aneuploidy is associated with poor patient outcome for a large variety of tumor types, including breast, colon, and renal cell carcinoma. The Renal cell carcinoma (RCC) is a heterogeneous carcinoma consisting of different histologic types. The clear renal cell carcinoma (ccRCC) is the most common subtype and represents 85% of the RCC. Central to the biology of the ccRCC is the loss of function of the Von HippelLindau gene, but is also associated with genetic instability that could be caused by abrogation of the cell cycle mitotic spindle checkpoint and may involve the Aurora kinases, which regulate centrosome maturation. Aneuploidy can also result from the loss of cellcell adhesion and apicalbasal cell polarity that also may be regulated by the mitotic kinases (polo-like kinase 1, casein kinase 2, doublecortin-like kinase 1, and Aurora kinases). In this review, we describe the non-mitotic unconventional functions of these kinases in renal tumorigenesis. PMID:26579493

  15. Endoscopic features suggesting gastric cancer in biopsy-proven gastric adenoma with high-grade neoplasia

    PubMed Central

    Kim, Jung Ho; Kim, Yoon Jae; An, Jungsuk; Lee, Jong Joon; Cho, Jae Hee; Kim, Kyoung Oh; Chung, Jun-Won; Kwon, Kwang An; Park, Dong Kyun; Kim, Ju Hyun

    2014-01-01

    AIM: To elucidate the endoscopic features that predict the cancer following endoscopic submucosal dissection (ESD) in patients with high-grade neoplasia (HGN). METHODS: We retrospectively analyzed the medical records of patients who underwent ESD of gastric neoplasms from January 2007 to September 2010. ESD was performed in 555 cases involving 550 patients. A total of 112 lesions from 110 consecutive patients were initially diagnosed as HGN without cancer by forceps biopsy, and later underwent ESD. We classified lesions into two groups according to histologic discrepancies between the biopsy and ESD diagnosis. Gastric adenoma in the final diagnosis by ESD specimens were defined as adenoma group. Lesions with coexisting cancer after ESD were defined as cancer group. RESULTS: The mean age was 65.3 years, and 81 patients were male. There was no significant difference in the age or gender distribution between the adenoma (n = 52) and cancer (n = 60) groups. Thirty-six of these lesions (32.1%) showed histologic concordance between the forceps biopsy and ESD specimens, 16 (14.3%) showed a downgraded histology (low-grade neoplasia), and 60 (53.6%) showed an upgraded histology (cancer). A red color change of the mucosal surface on endoscopy was found in 27/52 (51.9%) of cases in the adenoma group and in 46/60 (76.7%) of cases in the cancer group (P = 0.006). Ulceration of the mucosal surface on endoscopy was found in 5 (9.6%) of 52 lesions in the adenoma group and in 17 (28.3%) of 60 lesions in the cancer group (P = 0.013). In the multivariate analysis, a reddish surface color change and mucosal ulceration were significant predictive factors correlated with cancer after ESD of the HGN by forceps biopsy. CONCLUSION: HGN with a red color change or mucosal ulceration correlated with the presence of gastric cancer. These finding may help to guide the diagnosis and treatment. PMID:25232257

  16. An improved high order texture features extraction method with application to pathological diagnosis of colon lesions for CT colonography

    NASA Astrophysics Data System (ADS)

    Song, Bowen; Zhang, Guopeng; Lu, Hongbing; Wang, Huafeng; Han, Fangfang; Zhu, Wei; Liang, Zhengrong

    2014-03-01

    Differentiation of colon lesions according to underlying pathology, e.g., neoplastic and non-neoplastic, is of fundamental importance for patient management. Image intensity based textural features have been recognized as a useful biomarker for the differentiation task. In this paper, we introduce high order texture features, beyond the intensity, such as gradient and curvature, for that task. Based on the Haralick texture analysis method, we introduce a virtual pathological method to explore the utility of texture features from high order differentiations, i.e., gradient and curvature, of the image intensity distribution. The texture features were validated on database consisting of 148 colon lesions, of which 35 are non-neoplastic lesions, using the random forest classifier and the merit of area under the curve (AUC) of the receiver operating characteristics. The results show that after applying the high order features, the AUC was improved from 0.8069 to 0.8544 in differentiating non-neoplastic lesion from neoplastic ones, e.g., hyperplastic polyps from tubular adenomas, tubulovillous adenomas and adenocarcinomas. The experimental results demonstrated that texture features from the higher order images can significantly improve the classification accuracy in pathological differentiation of colorectal lesions. The gain in differentiation capability shall increase the potential of computed tomography (CT) colonography for colorectal cancer screening by not only detecting polyps but also classifying them from optimal polyp management for the best outcome in personalized medicine.

  17. Proteins related to the spindle and checkpoint mitotic emphasize the different pathogenesis of hypoplastic MDS.

    PubMed

    Heredia, Fabiola Fernandes; de Sousa, Juliana Cordeiro; Ribeiro Junior, Howard Lopes; Carvalho, Alex Fiorini; Magalhaes, Silvia Maria Meira; Pinheiro, Ronald Feitosa

    2014-02-01

    Some studies show that alterations in expression of proteins related to mitotic spindle (AURORAS KINASE A and B) and mitotic checkpoint (CDC20 and MAD2L1) are involved in chromosomal instability and tumor progression in various solid and hematologic malignancies. This study aimed to evaluate these genes in MDS patients. The cytogenetics analysis was carried out by G-banding, AURKA and AURKB amplification was performed using FISH, and AURKA, AURKB, CDC20 and MAD2L1 gene expression was performed by qRT-PCR in 61 samples of bone marrow from MDS patients. AURKA gene amplification was observed in 10% of the cases, which also showed higher expression levels than the control group (p=0.038). Patients with normo/hypercellular BM presented significantly higher expression levels than hypocellular BM patients, but normo and hypercellular BM groups did not differ. After logistic regression analysis, our results showed that HIGH expression levels were associated with increased risk of developing normo/hypercellular MDS. It also indicated that age is associated with AURKA, CDC20 and MAD2L1 HIGH expression levels. The distinct expression of hypocellular patients emphasizes the prognostic importance of cellularity to MDS. The amplification/high expression of AURKA suggests that the increased expression of this gene may be related to the pathogenesis of disease. PMID:24314588

  18. Giant cell tumour of tendon sheath (localised nodular tenosynovitis): clinicopathological features of 71 cases

    PubMed Central

    Monaghan, H; Salter, D; Al-Nafussi, A

    2001-01-01

    Aims/BackgroundGiant cell tumour of the tendon sheath (GCTTS) is regarded as the most common neoplasm of the hand that can recur after excision. The objective of this study was to review a series of cases in our department and to determine any clinical or pathological features that might predict the likelihood of recurrence. MethodsClinical data, obtained from pathology request forms and in patient notes, along with the gross and microscopic appearances of 71 cases of GCTTS were evaluated. ResultsClinical features and pathological features identified were similar to those of previous studies. In comparison with previous studies a higher mitotic count (range, 121 mitoses/10 high power fields (HPF); mean, 5/10 HPF) was noted in all cases, irrespective of recurrence and numerous apoptotic bodies (up to 30/10 HPF), mainly formed from osteoclast-like giant cells, were present. ConclusionsGCTTS is a relatively rare soft tissue tumour of uncertain histiogenesis. Mitotic and apoptotic figures are a common feature and do not indicate clinical behaviour. Complete local excision is the treatment of choice. Key Words: giant cell tumour tendon sheath apoptosis osteoclasts PMID:11328844

  19. Condensin targets and reduces unwound DNA structures associated with transcription in mitotic chromosome condensation

    PubMed Central

    Sutani, Takashi; Sakata, Toyonori; Nakato, Ryuichiro; Masuda, Koji; Ishibashi, Mai; Yamashita, Daisuke; Suzuki, Yutaka; Hirano, Tatsuya; Bando, Masashige; Shirahige, Katsuhiko

    2015-01-01

    Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells. Here we show that condensin, which is essential for assembling condensed chromosomes, helps to preclude the detrimental effects of gene transcription on mitotic condensation. ChIP-seq profiling reveals that the fission yeast condensin preferentially binds to active protein-coding genes in a transcription-dependent manner during mitosis. Pharmacological and genetic attenuation of transcription largely rescue bulk chromosome segregation defects observed in condensin mutants. We also demonstrate that condensin is associated with and reduces unwound DNA segments generated by transcription, providing a direct link between an in vitro activity of condensin and its in vivo function. The human condensin isoform condensin I also binds to unwound DNA regions at the transcription start sites of active genes, implying that our findings uncover a fundamental feature of condensin complexes. PMID:26204128

  20. Cbx2 stably associates with mitotic chromosomes via a PRC2- or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes

    PubMed Central

    Zhen, Chao Yu; Duc, Huy Nguyen; Kokotovic, Marko; Phiel, Christopher J.; Ren, Xiaojun

    2014-01-01

    Polycomb group (PcG) proteins are epigenetic transcriptional factors that repress key developmental regulators and maintain cellular identity through mitosis via a poorly understood mechanism. Using quantitative live-cell imaging in mouse ES cells and tumor cells, we demonstrate that, although Polycomb repressive complex (PRC) 1 proteins (Cbx-family proteins, Ring1b, Mel18, and Phc1) exhibit variable capacities of association with mitotic chromosomes, Cbx2 overwhelmingly binds to mitotic chromosomes. The recruitment of Cbx2 to mitotic chromosomes is independent of PRC1 or PRC2, and Cbx2 is needed to recruit PRC1 complex to mitotic chromosomes. Quantitative fluorescence recovery after photobleaching analysis indicates that PRC1 proteins rapidly exchange at interphasic chromatin. On entry into mitosis, Cbx2, Ring1b, Mel18, and Phc1 proteins become immobilized at mitotic chromosomes, whereas other Cbx-family proteins dynamically bind to mitotic chromosomes. Depletion of PRC1 or PRC2 protein has no effect on the immobilization of Cbx2 on mitotic chromosomes. We find that the N-terminus of Cbx2 is needed for its recruitment to mitotic chromosomes, whereas the C-terminus is required for its immobilization. Thus these results provide fundamental insights into the molecular mechanisms of epigenetic inheritance. PMID:25232004

  1. Human Nek7-interactor RGS2 is required for mitotic spindle organization

    PubMed Central

    de Souza, Edmarcia Elisa; Hehnly, Heidi; Perez, Arina Marina; Meirelles, Gabriela Vaz; Smetana, Juliana Helena Costa; Doxsey, Stephen; Kobarg, Jörg

    2015-01-01

    The mitotic spindle apparatus is composed of microtubule (MT) networks attached to kinetochores organized from 2 centrosomes (a.k.a. spindle poles). In addition to this central spindle apparatus, astral MTs assemble at the mitotic spindle pole and attach to the cell cortex to ensure appropriate spindle orientation. We propose that cell cycle-related kinase, Nek7, and its novel interacting protein RGS2, are involved in mitosis regulation and spindle formation. We found that RGS2 localizes to the mitotic spindle in a Nek7-dependent manner, and along with Nek7 contributes to spindle morphology and mitotic spindle pole integrity. RGS2-depletion leads to a mitotic-delay and severe defects in the chromosomes alignment and congression. Importantly, RGS2 or Nek7 depletion or even overexpression of wild-type or kinase-dead Nek7, reduced γ-tubulin from the mitotic spindle poles. In addition to causing a mitotic delay, RGS2 depletion induced mitotic spindle misorientation coinciding with astral MT-reduction. We propose that these phenotypes directly contribute to a failure in mitotic spindle alignment to the substratum. In conclusion, we suggest a molecular mechanism whereupon Nek7 and RGS2 may act cooperatively to ensure proper mitotic spindle organization. PMID:25664600

  2. Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression

    PubMed Central

    ORegan, Laura; Sampson, Josephina; Richards, Mark W.; Knebel, Axel; Roth, Daniel; Hood, Fiona E.; Straube, Anne; Royle, Stephen J.; Bayliss, Richard

    2015-01-01

    Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust bipolar spindle capable of efficient chromosome congression. Mechanistically, Hsp72 associates with the K-fiberstabilizing proteins, ch-TOG and TACC3, and promotes their interaction with each other and recruitment to spindle microtubules (MTs). Targeting of Hsp72 to the mitotic spindle is dependent on phosphorylation at Thr-66 within its nucleotide-binding domain by the Nek6 kinase. Phosphorylated Hsp72 concentrates on spindle poles and sites of MTkinetochore attachment. A phosphomimetic Hsp72 mutant rescued defects in K-fiber assembly, ch-TOG/TACC3 recruitment and mitotic progression that also resulted from Nek6 depletion. We therefore propose that Nek6 facilitates association of Hsp72 with the mitotic spindle, where it promotes stable K-fiber assembly through recruitment of the ch-TOGTACC3 complex. PMID:25940345

  3. A monoclonal antibody specific for prophase phosphorylation of histone deacetylase 1: a readout for early mitotic cells.

    PubMed

    Segr, Chiara V; Senese, Silvia; Loponte, Sara; Santaguida, Stefano; Soffientini, Paolo; Grigorean, Gabriela; Cinquanta, Mario; Ossolengo, Giuseppe; Seiser, Christian; Chiocca, Susanna

    2016-01-01

    Histone deacetylases (HDACs) are modification enzymes that regulate a plethora of biological processes. HDAC1, a crucial epigenetic modifier, is deregulated in cancer and subjected to a variety of post-translational modifications. Here, we describe the generation of a new monoclonal antibody that specifically recognizes a novel highly dynamic prophase phosphorylation of serine 406-HDAC1, providing a powerful tool for detecting early mitotic cells. PMID:26467746

  4. Tumor treating fields perturb the localization of septins and cause aberrant mitotic exit.

    PubMed

    Gera, Nidhi; Yang, Aaron; Holtzman, Talia S; Lee, Sze Xian; Wong, Eric T; Swanson, Kenneth D

    2015-01-01

    The anti-tumor effects of chemotherapy and radiation are thought to be mediated by triggering G1/S or G2/M cell cycle checkpoints, while spindle poisons, such as paclitaxel, block metaphase exit by initiating the spindle assembly checkpoint. In contrast, we have found that 150 kilohertz (kHz) alternating electric fields, also known as Tumor Treating Fields (TTFields), perturbed cells at the transition from metaphase to anaphase. Cells exposed to the TTFields during mitosis showed normal progression to this point, but exhibited uncontrolled membrane blebbing that coincided with metaphase exit. The ability of such alternating electric fields to affect cellular physiology is likely to be dependent on their interactions with proteins possessing high dipole moments. The mitotic Septin complex consisting of Septin 2, 6 and 7, possesses a high calculated dipole moment of 2711 Debyes (D) and plays a central role in positioning the cytokinetic cleavage furrow, and governing its contraction during ingression. We showed that during anaphase, TTFields inhibited Septin localization to the anaphase spindle midline and cytokinetic furrow, as well as its association with microtubules during cell attachment and spreading on fibronectin. After aberrant metaphase exit as a consequence of TTFields exposure, cells exhibited aberrant nuclear architecture and signs of cellular stress including an overall decrease in cellular proliferation, followed by apoptosis that was strongly influenced by the p53 mutational status. Thus, TTFields are able to diminish cell proliferation by specifically perturbing key proteins involved in cell division, leading to mitotic catastrophe and subsequent cell death. PMID:26010837

  5. Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit

    PubMed Central

    Holtzman, Talia S.; Lee, Sze Xian; Wong, Eric T.; Swanson, Kenneth D.

    2015-01-01

    The anti-tumor effects of chemotherapy and radiation are thought to be mediated by triggering G1/S or G2/M cell cycle checkpoints, while spindle poisons, such as paclitaxel, block metaphase exit by initiating the spindle assembly checkpoint. In contrast, we have found that 150 kilohertz (kHz) alternating electric fields, also known as Tumor Treating Fields (TTFields), perturbed cells at the transition from metaphase to anaphase. Cells exposed to the TTFields during mitosis showed normal progression to this point, but exhibited uncontrolled membrane blebbing that coincided with metaphase exit. The ability of such alternating electric fields to affect cellular physiology is likely to be dependent on their interactions with proteins possessing high dipole moments. The mitotic Septin complex consisting of Septin 2, 6 and 7, possesses a high calculated dipole moment of 2711 Debyes (D) and plays a central role in positioning the cytokinetic cleavage furrow, and governing its contraction during ingression. We showed that during anaphase, TTFields inhibited Septin localization to the anaphase spindle midline and cytokinetic furrow, as well as its association with microtubules during cell attachment and spreading on fibronectin. After aberrant metaphase exit as a consequence of TTFields exposure, cells exhibited aberrant nuclear architecture and signs of cellular stress including an overall decrease in cellular proliferation, followed by apoptosis that was strongly influenced by the p53 mutational status. Thus, TTFields are able to diminish cell proliferation by specifically perturbing key proteins involved in cell division, leading to mitotic catastrophe and subsequent cell death. PMID:26010837

  6. High albedo dune features suggest past dune migration and possible geochemical cementation of aeolian sediments on Mars

    NASA Astrophysics Data System (ADS)

    Gardin, Emilie; Bourke, Mary C.; Allemand, Pascal; Quantin, Cathy

    2011-04-01

    High albedo features are identified in association with barchan dunes in an equatorial inter-crater dune field on Mars using images from the MRO mission. This paper describes the morphometric properties of these features and their association with the present barchan dune field. We propose that these features are cemented aeolian deposits that form at the foot of the dune avalanche face. A possible terrestrial analog exists at White Sands National Monument, in south-central New Mexico, USA. The presence of these features suggests past episodes of dune migration in inter-crater dunefields and liquid water in the near sub-surface in sufficient quantity to cause the cementation of aeolian dune sediment.

  7. Comparison of Aerosol Classification from Airborne High Spectral Resolution Lidar and the CALIPSO Vertical Feature Mask

    NASA Astrophysics Data System (ADS)

    Burton, S. P.; Ferrare, R. A.; Omar, A. H.; Hostetler, C. A.; Hair, J. W.; Rogers, R.; Obland, M. D.; Butler, C. F.; Cook, A. L.; Harper, D. B.

    2012-12-01

    The NASA Langley Research Center (LaRC) airborne High Spectral Resolution Lidar (HSRL-1) on the NASA B200 aircraft has acquired large datasets of aerosol extinction (532nm), backscatter (532 and 1064nm), and depolarization (532 and 1064nm) profiles during 349 science flights in 19 field missions across North America since 2006. The extinction-to-backscatter ratio ("lidar ratio"), aerosol depolarization ratios, and backscatter color ratio measurements from HSRL-1 are scale-invariant parameters that depend on aerosol type but not concentration. These four aerosol intensive parameters are combined to qualitatively classify HSRL aerosol measurements into eight separate composition types. The classification methodology uses models formed from "training cases" with known aerosol type. The remaining measurements are then compared with these models using the Mahalanobis distance. Aerosol products from the CALIPSO satellite include aerosol type information as well, which is used as input to the CALIPSO aerosol retrieval. CALIPSO aerosol types are inferred using a mix of aerosol loading-dependent parameters, estimated aerosol depolarization, and location, altitude, and surface type information. The HSRL instrument flies beneath the CALIPSO satellite orbit track, presenting the opportunity for comparisons between the HSRL aerosol typing and the CALIPSO Vertical Feature Mask Aerosol Subtype product, giving insight into the performance of the CALIPSO aerosol type algorithm. We find that the aerosol classification from the two instruments frequently agree for marine aerosols and pure dust, and somewhat less frequently for pollution and smoke. In addition, the comparison suggests that the CALIPSO polluted dust type is overly inclusive, encompassing cases of dust combined with marine aerosol as well as cases without much evidence of dust. Qualitative classification of aerosol type combined with quantitative profile measurements of aerosol backscatter and extinction has many useful applications. The HSRL products are used to apportion AOT by type and vertical location in the column, and to characterize the frequency of cases where multiple types are present in the column. Resolving scenes with multiple types in the column is not possible with passive imaging radiometer and polarimeter measurements. The HSRL aerosol type also has higher resolution than the CALIPSO layer-wise product and provides insight into the performance of CALIPSO layer separation. Information about the vertical distribution of aerosol types is useful for estimating radiative forcing, understanding aerosol lifetime and transport, and assessing the predictions of transport models. CALIPSO has been a pathfinder, providing the first long-term global data set of aerosol vertical distribution. Based on our results, a future satellite lidar similar to CALIPSO, but with the addition of polarization sensitivity at 1064 nm and the HSRL technique at 532 nm, could provide a significant advance in characterizing the vertical distribution of aerosol.

  8. Ribbon plastic optical fiber linked optical transmitter and receiver modules featuring a high alignment tolerance.

    PubMed

    Lee, Hak-Soon; Park, Jun-Young; Cha, Sang-Mo; Lee, Sang-Shin; Hwang, Gyo-Sun; Son, Yung-Sung

    2011-02-28

    Ribbon plastic optical fiber (POF) linked four-channel optical transmitter (Tx) and receiver (Rx) modules have been proposed and realized featuring an excellent alignment tolerance. The two modules share a common configuration involving an optical sub-assembly (OSA) with vertical cavity surface emitting lasers (VCSELs)/photodetectors (PDs), and their driver ICs, which are integrated onto a single printed circuit board (PCB) substrate. The OSA includes an alignment structure, a beam router and a fiber guide, which were produced by using plastic injection molding. We have accomplished a fully passive alignment between the VCSELs/PDs and the ribbon POF by taking advantage of the alignment structure that serves as a reference during the alignment of the constituent parts of the OSA. The electrical link, which largely determines the operation speed, has been remarkably shortened, due to a direct wire-bonding between the VCSELs/PDs and the driver circuits. The light sources and the detectors can be individually positioned, thereby overcoming the pitch limitations of the ribbon POF, which is made up of perfluorinated graded-index (GI) POF with a 62.5 ?m core diameter. The overall alignment tolerance was first assessed by observing the optical coupling efficiency in terms of VCSEL/PD misalignment. The horizontal and vertical 3-dB alignment tolerances were about 20 ?m and 150 ?m for the Tx and 50 ?m and over 200 ?m for the Rx, respectively. The VCSEL-to-POF coupling loss for the Tx and the POF-to-PD loss for the Rx were 3.25 dB and 1.35 dB at a wavelength of 850 nm, respectively. Subsequently, a high-speed signal at 3.2 Gb/s was satisfactorily delivered via the Tx and Rx modules over a temperature range of -30 to 70C with no significant errors; the channel crosstalk was below -30 dB. Finally, the performance of the prepared modules was verified by transmitting a 1080p HDMI video supplied by a Bluelay player to an LCD TV. PMID:21369260

  9. Excess of miRNA-378a-5p perturbs mitotic fidelity and correlates with breast cancer tumourigenesis in vivo

    PubMed Central

    Winsel, S; Mki-Jouppila, J; Tambe, M; Aure, M R; Pruikkonen, S; Salmela, A-L; Halonen, T; Leivonen, S-K; Kallio, L; Brresen-Dale, A-L; Kallio, M J

    2014-01-01

    Background: Optimal expression and proper function of key mitotic proteins facilitate control and repair processes that aim to prevent loss or gain of chromosomes, a hallmark of cancer. Altered expression of small regulatory microRNAs is associated with tumourigenesis and metastasis but the impact on mitotic signalling has remained unclear. Methods: Cell-based high-throughput screen identified miR-378a-5p as a mitosis perturbing microRNA. Transient transfections, immunofluorescence, western blotting, time-lapse microscopy, FISH and reporter assays were used to characterise the mitotic anomalies by excess miR-378a-5p. Analysis of microRNA profiles in breast tumours was performed. Results: Overexpression of miR-378a-5p induced numerical chromosome changes in cells and abrogated taxol-induced mitotic block via premature inactivation of the spindle assembly checkpoint. Moreover, excess miR-378a-5p triggered receptor tyrosine kinaseMAP kinase pathway signalling, and was associated with suppression of Aurora B kinase. In breast cancer in vivo, we found that high miR-378a-5p levels correlate with the most aggressive, poorly differentiated forms of cancer. Interpretation: Downregulation of Aurora B by excess miR-378a-5p can explain the observed microtubule drug resistance and increased chromosomal imbalance in the microRNA-overexpressing cells. The results suggest that breast tumours may deploy high miR-378a-5p levels to gain growth advantage and antagonise taxane therapy. PMID:25268374

  10. An Educational System to Help Students Assess Website Features and Identify High-Risk Websites

    ERIC Educational Resources Information Center

    Kajiyama, Tomoko; Echizen, Isao

    2015-01-01

    Purpose: The purpose of this paper is to propose an effective educational system to help students assess Web site risk by providing an environment in which students can better understand a Web site's features and determine the risks of accessing the Web site for themselves. Design/methodology/approach: The authors have enhanced a prototype

  11. Cardinality as a highly descriptive feature in myoelectric pattern recognition for decoding motor volition

    PubMed Central

    Ortiz-Catalan, Max

    2015-01-01

    Accurate descriptors of muscular activity play an important role in clinical practice and rehabilitation research. Such descriptors are features of myoelectric signals extracted from sliding time windows. A wide variety of myoelectric features have been used as inputs to pattern recognition algorithms that aim to decode motor volition. The output of these algorithms can then be used to control limb prostheses, exoskeletons, and rehabilitation therapies. In the present study, cardinality is introduced and compared with traditional time-domain (Hudgins' set) and other recently proposed myoelectric features (for example, rough entropy). Cardinality was found to consistently outperform other features, including those that are more sophisticated and computationally expensive, despite variations in sampling frequency, time window length, contraction dynamics, type, and number of movements (single or simultaneous), and classification algorithms. Provided that the signal resolution is kept between 12 and 14 bits, cardinality improves myoelectric pattern recognition for the prediction of motion volition. This technology is instrumental for the rehabilitation of amputees and patients with motor impairments where myoelectric signals are viable. All code and data used in this work is available online within BioPatRec. PMID:26578873

  12. An Educational System to Help Students Assess Website Features and Identify High-Risk Websites

    ERIC Educational Resources Information Center

    Kajiyama, Tomoko; Echizen, Isao

    2015-01-01

    Purpose: The purpose of this paper is to propose an effective educational system to help students assess Web site risk by providing an environment in which students can better understand a Web site's features and determine the risks of accessing the Web site for themselves. Design/methodology/approach: The authors have enhanced a prototype…

  13. Analyzing fine-scale wetland composition using high resolution imagery and texture features

    NASA Astrophysics Data System (ADS)

    Szantoi, Zoltan; Escobedo, Francisco; Abd-Elrahman, Amr; Smith, Scot; Pearlstine, Leonard

    2013-08-01

    In order to monitor natural and anthropogenic disturbance effects to wetland ecosystems, it is necessary to employ both accurate and rapid mapping of wet graminoid/sedge communities. Thus, it is desirable to utilize automated classification algorithms so that the monitoring can be done regularly and in an efficient manner. This study developed a classification and accuracy assessment method for wetland mapping of at-risk plant communities in marl prairie and marsh areas of the Everglades National Park. Maximum likelihood (ML) and Support Vector Machine (SVM) classifiers were tested using 30.5 cm aerial imagery, the normalized difference vegetation index (NDVI), first and second order texture features and ancillary data. Additionally, appropriate window sizes for different texture features were estimated using semivariogram analysis. Findings show that the addition of NDVI and texture features increased classification accuracy from 66.2% using the ML classifier (spectral bands only) to 83.71% using the SVM classifier (spectral bands, NDVI and first order texture features).

  14. Cardinality as a highly descriptive feature in myoelectric pattern recognition for decoding motor volition.

    PubMed

    Ortiz-Catalan, Max

    2015-01-01

    Accurate descriptors of muscular activity play an important role in clinical practice and rehabilitation research. Such descriptors are features of myoelectric signals extracted from sliding time windows. A wide variety of myoelectric features have been used as inputs to pattern recognition algorithms that aim to decode motor volition. The output of these algorithms can then be used to control limb prostheses, exoskeletons, and rehabilitation therapies. In the present study, cardinality is introduced and compared with traditional time-domain (Hudgins' set) and other recently proposed myoelectric features (for example, rough entropy). Cardinality was found to consistently outperform other features, including those that are more sophisticated and computationally expensive, despite variations in sampling frequency, time window length, contraction dynamics, type, and number of movements (single or simultaneous), and classification algorithms. Provided that the signal resolution is kept between 12 and 14 bits, cardinality improves myoelectric pattern recognition for the prediction of motion volition. This technology is instrumental for the rehabilitation of amputees and patients with motor impairments where myoelectric signals are viable. All code and data used in this work is available online within BioPatRec. PMID:26578873

  15. A high-frequency Doppler feature in the power spectra of simulated GRMHD black hole accretion disks

    SciTech Connect

    Wellons, Sarah; Zhu, Yucong; Narayan, Ramesh; McClintock, Jeffrey E.; Psaltis, Dimitrios

    2014-04-20

    Black hole binaries exhibit a wide range of variability phenomena, from large-scale state changes to broadband noise and quasi-periodic oscillations, but the physical nature of much of this variability is poorly understood. We examine the variability properties of three GRMHD simulations of thin accretion disks around black holes of varying spin, producing light curves and power spectra as would be seen by observers. We find that the simulated power spectra show a broad feature at high frequency, which increases in amplitude with the inclination of the observer. We show that this high-frequency feature is a product of the Doppler effect and that its location is a function of the mass and spin of the black hole. This Doppler feature demonstrates that power spectral properties of the accretion disk can be tied to, and potentially used to determine, physical properties of the black hole.

  16. Influence of the circadian rhythm in cell division on radiation-induced mitotic delay in vivo

    SciTech Connect

    Rubin, N.H.

    1982-01-01

    Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, to a lesser extent, degree of recovery.

  17. Genome-wide siRNA screen reveals coupling between mitotic apoptosis and adaptation.

    PubMed

    Daz-Martnez, Laura A; Karamysheva, Zemfira N; Warrington, Ross; Li, Bing; Wei, Shuguang; Xie, Xian-Jin; Roth, Michael G; Yu, Hongtao

    2014-09-01

    The antimitotic anti-cancer drugs, including taxol, perturb spindle dynamics, and induce prolonged, spindle checkpoint-dependent mitotic arrest in cancer cells. These cells then either undergo apoptosis triggered by the intrinsic mitochondrial pathway or exit mitosis without proper cell division in an adaptation pathway. Using a genome-wide small interfering RNA (siRNA) screen in taxol-treated HeLa cells, we systematically identify components of the mitotic apoptosis and adaptation pathways. We show that the Mad2 inhibitor p31(comet) actively promotes mitotic adaptation through cyclin B1 degradation and has a minor separate function in suppressing apoptosis. Conversely, the pro-apoptotic Bcl2 family member, Noxa, is a critical initiator of mitotic cell death. Unexpectedly, the upstream components of the mitochondrial apoptosis pathway and the mitochondrial fission protein Drp1 contribute to mitotic adaption. Our results reveal crosstalk between the apoptosis and adaptation pathways during mitotic arrest. PMID:25024437

  18. Genome-wide siRNA screen reveals coupling between mitotic apoptosis and adaptation

    PubMed Central

    Daz-Martnez, Laura A; Karamysheva, Zemfira N; Warrington, Ross; Li, Bing; Wei, Shuguang; Xie, Xian-Jin; Roth, Michael G; Yu, Hongtao

    2014-01-01

    The antimitotic anti-cancer drugs, including taxol, perturb spindle dynamics, and induce prolonged, spindle checkpoint-dependent mitotic arrest in cancer cells. These cells then either undergo apoptosis triggered by the intrinsic mitochondrial pathway or exit mitosis without proper cell division in an adaptation pathway. Using a genome-wide small interfering RNA (siRNA) screen in taxol-treated HeLa cells, we systematically identify components of the mitotic apoptosis and adaptation pathways. We show that the Mad2 inhibitor p31comet actively promotes mitotic adaptation through cyclin B1 degradation and has a minor separate function in suppressing apoptosis. Conversely, the pro-apoptotic Bcl2 family member, Noxa, is a critical initiator of mitotic cell death. Unexpectedly, the upstream components of the mitochondrial apoptosis pathway and the mitochondrial fission protein Drp1 contribute to mitotic adaption. Our results reveal crosstalk between the apoptosis and adaptation pathways during mitotic arrest. PMID:25024437

  19. Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae.

    PubMed

    Magwene, Paul M; Kay?k?, mr; Granek, Joshua A; Reininga, Jennifer M; Scholl, Zackary; Murray, Debra

    2011-02-01

    We carried out a population genomic survey of Saccharomyces cerevisiae diploid isolates and find that many budding yeast strains have high levels of genomic heterozygosity, much of which is likely due to outcrossing. We demonstrate that variation in heterozygosity among strains is correlated with a life-history trade-off that involves how readily yeast switch from asexual to sexual reproduction under nutrient stress. This trade-off is reflected in a negative relationship between sporulation efficiency and pseudohyphal development and correlates with variation in the expression of RME1, a transcription factor with pleiotropic effects on meiosis and filamentous growth. Selection for alternate life-history strategies in natural versus human-associated environments likely contributes to differential maintenance of genomic heterozygosity through its effect on the frequency that yeast lineages experience sexual cycles and hence the opportunity for inbreeding. In addition to elevated levels of heterozygosity, many strains exhibit large genomic regions of loss-of-heterozygosity (LOH), suggesting that mitotic recombination has a significant impact on genetic variation in this species. This study provides new insights into the roles that both outcrossing and mitotic recombination play in shaping the genome architecture of Saccharomyces cerevisiae. This study also provides a unique case where stark differences in the genomic distribution of genetic variation among individuals of the same species can be largely explained by a life-history trade-off. PMID:21245305

  20. Active DNA demethylation in post-mitotic neurons: a reason for optimism.

    PubMed

    Gavin, David P; Chase, Kayla A; Sharma, Rajiv P

    2013-12-01

    Over the last several years proteins involved in base excision repair (BER) have been implicated in active DNA demethylation. We review the literature supporting BER as a means of active DNA demethylation, and explain how the various components function and cooperate to remove the potentially most enduring means of epigenetic gene regulation. Recent evidence indicates that the same pathways implicated during periods of widespread DNA demethylation, such as the erasure of methyl marks in the paternal pronucleus soon after fertilization, are operational in post-mitotic neurons. Neuronal functional identities, defined here as the result of a combination of neuronal subtype, location, and synaptic connections are largely maintained through DNA methylation. Chronic mental illnesses, such as schizophrenia, may be the result of both altered neurotransmitter levels and neurons that have assumed dysfunctional neuronal identities. A limitation of most current psychopharmacological agents is their focus on the former, while not addressing the more profound latter pathophysiological process. Previously, it was believed that active DNA demethylation in post-mitotic neurons was rare if not impossible. If this were the case, then reversing the factors that maintain neuronal identity, would be highly unlikely. The emergence of an active DNA demethylation pathway in the brain is a reason for great optimism in psychiatry as it provides a means by which previously pathological neurons may be reprogrammed to serve a more favorable role. Agents targeting epigenetic processes have shown much promise in this regard, and may lead to substantial gains over traditional pharmacological approaches. PMID:23958448

  1. Mitotic disturbances and micronucleus induction in Syrian hamster embryo fibroblast cells caused by asbestos fibers.

    PubMed Central

    Dopp, E; Saedler, J; Stopper, H; Weiss, D G; Schiffmann, D

    1995-01-01

    Asbestos and other mineral fibers have long been known to induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We investigated the occurrence of mitotic disturbances induced by asbestos (amosite, crocidolite, chrysotile) in an in vitro approach using Syrian hamster embryo (SHE) fibroblast cells. The following endpoints were investigated: micronucleus formation as a result of mitotic disturbances and characterization of the induced micronucleus population by kinetochore staining and visualization of the spindle apparatus. Supravital UV-microscopy was used to analyze changes in interphase chromatin structure, impaired chromatid separation, and blocked cytokinesis. All three asbestos fiber types induced a high frequency of micronucleus formation in SHE cells (> 200/2000 cells) in a dose-dependent manner (0.1-5.0 micrograms/cm2), with a maximum between 48 hr and 66 hr exposure time. At higher concentrations (more than 5.0 micrograms/cm2) the micronucleus formation decreased again as a result of increased toxicity. Kinetochore staining of micronuclei revealed that 48 +/- 2% of asbestos-induced micronuclei reacted positively with CREST (antikinetochore) serum. Furthermore, spindle apparatus deformations occurred in cells with disturbed metaphases and anaphases, while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss and breakage of chromosomes in the absence of direct interaction with spindle fibers. Images Figure 1. Figure 2. Figure 3. A Figure 3. B Figure 3. C Figure 3. D Figure 3. E Figure 3. F PMID:7768228

  2. Mitotic activity in chondrocyte transplantation from the in vitro phase to the in vivo phase.

    PubMed

    Peretti, G M; Caruso, E M; Papini Zorli, I; Albisetti, W

    2000-01-01

    The transplantation of devitalized allogenic matrices vehiculating autologous chondrocytes, previously isoled and seeded on them could be a solution to the problem of repairing lesions of the joint cartilage. For the matrix/cell "composite" to be "graftable" the cells must continue to duplicate and produce cartilaginous matrix even after transport in vivo. The present study analyzes the mitotic activity of chondrocytes planted on devitalized allogenic cartilage and grafted in living animals. Chondrocytes of joint cartilage of lambs were isolated enzymatically and then seeded in vitro on devitalized allogenic cartilaginous matrices for 3 weeks. At the end of the co-culture period, these matrix/chondrocyte composites were transplanted in subcutaneous pockets of athymic mice. The experimental and control samples were evaluated subsequent to explantation by histological study and incorporation of tritiated thymidine. The results obtained revealed an important decrease in the values for the incorporation of thymidine beginning from experimental time 0 (pre-implant evaluation) up to day 28 after implantation, followed by a mild increase at the experimental time of 42 days. This study demonstrated the tendency of articular chondrocytes cultivated in vitro and subsequently transplanted in vivo on a support of devitalized allogenic cartilaginous matrix to modify mitotic activity from very high values for the first experimental times, typical of the in vitro phases of cellular expansion, to very low values, more similar to the behavior of articular chondrocytes in vivo. PMID:11569091

  3. Regulation of Mitotic Spindle Disassembly by an Environmental Stress-Sensing Pathway in Budding Yeast

    PubMed Central

    Pigula, Adrianne; Drubin, David G.; Barnes, Georjana

    2014-01-01

    Timely spindle disassembly is essential for coordination of mitotic exit with cytokinesis. In the budding yeast Saccharomyces cerevisiae, the microtubule-associated protein She1 functions in one of at least three parallel pathways that promote spindle disassembly. She1 phosphorylation by the Aurora kinase Ipl1 facilitates a role for She1 in late anaphase, when She1 contributes to microtubule depolymerization and shrinkage of spindle halves. By examining the genetic interactions of known spindle disassembly genes, we identified three genes in the environmental stress-sensing HOG (high-osmolarity glycerol response) pathway, SHO1, PBS2, and HOG1, and found they are necessary for proper localization of She1 to the anaphase spindle and for proper spindle disassembly. HOG pathway mutants exhibited spindle disassembly defects, as well as mislocalization of anillin-related proteins Boi1 and Boi2 from the bud neck. Moreover, Boi2, but not Boi1, plays a role in spindle disassembly that places Boi2 in a pathway with Sho1, Pbs2, and Hog1. Together, our data identify a process by which cells monitor events at the spindle and bud neck and describe a novel role for the HOG pathway in mitotic signaling. PMID:25213170

  4. Built-up Areas Extraction in High Resolution SAR Imagery based on the method of Multiple Feature Weighted Fusion

    NASA Astrophysics Data System (ADS)

    Liu, X.; Zhang, J. X.; Zhao, Z.; Ma, A. D.

    2015-06-01

    Synthetic aperture radar in the application of remote sensing technology is becoming more and more widely because of its all-time and all-weather operation, feature extraction research in high resolution SAR image has become a hot topic of concern. In particular, with the continuous improvement of airborne SAR image resolution, image texture information become more abundant. It's of great significance to classification and extraction. In this paper, a novel method for built-up areas extraction using both statistical and structural features is proposed according to the built-up texture features. First of all, statistical texture features and structural features are respectively extracted by classical method of gray level co-occurrence matrix and method of variogram function, and the direction information is considered in this process. Next, feature weights are calculated innovatively according to the Bhattacharyya distance. Then, all features are weighted fusion. At last, the fused image is classified with K-means classification method and the built-up areas are extracted after post classification process. The proposed method has been tested by domestic airborne P band polarization SAR images, at the same time, two groups of experiments based on the method of statistical texture and the method of structural texture were carried out respectively. On the basis of qualitative analysis, quantitative analysis based on the built-up area selected artificially is enforced, in the relatively simple experimentation area, detection rate is more than 90%, in the relatively complex experimentation area, detection rate is also higher than the other two methods. In the study-area, the results show that this method can effectively and accurately extract built-up areas in high resolution airborne SAR imagery.

  5. Enhancement of spontaneous mitotic recombination by the meiotic mutant spo11-1 in Saccharomyces cerevisiae

    SciTech Connect

    Bruschi, C.V.; Esposito, M.S.

    1983-12-01

    Both nonreciprocal and reciprocal mitotic recombination are enhanced by the recessive mutant spo11-1, which was previously shown to affect meiosis by decreasing recombination and increasing nondisjunction. The mitotic effects are not distributed equally in all chromosomal regions. The genotypes of mitotic recombinants in spo11-1/spo11-1 diploid cells provide further evidence that widely spaced chromosomal markers undergo coincident conversion in mitosis.

  6. Callous-Unemotional Features, Behavioral Inhibition, and Parenting: Independent Predictors of Aggression in a High-Risk Preschool Sample

    ERIC Educational Resources Information Center

    Kimonis, Eva R.; Frick, Paul J.; Boris, Neil W.; Smyke, Anna T.; Cornell, Amy H.; Farrell, Jamie M.; Zeanah, Charles H.

    2006-01-01

    A behaviorally-uninhibited temperament, callous-unemotional (CU) features, and harsh parenting have been associated with specific patterns of aggressive behavior in older children and adolescents. We tested the additive and interactive effects of these factors in predicting different types of aggressive behavior in a high-risk preschool sample.

  7. Change and Dilemma of School Feature Development of Three Junior High Schools in the Remote and Rural Areas of Taiwan

    ERIC Educational Resources Information Center

    Chen, Shan-Hua; Ho, Hsuan-Fu; Yang, Cheng-Cheng

    2012-01-01

    This research is based on qualitative approach and applies in-depth interview with three principals and administrators in three junior high schools located in the remote and rural areas of Taiwan. The aim of this paper was to explore the school feature development process in these three schools. The findings of this study were as follows: most of

  8. Working hard for recovery: mitotic kinases in the DNA damage checkpoint

    PubMed Central

    2013-01-01

    Cell division in mitosis is tightly regulated via a group of protein kinases. Activation of these mitotic kinases is inhibited by the DNA damage checkpoint that arrests the cell cycle in interphase and prevents mitotic entry. Interestingly, it has been shown that the DNA damage checkpoint is feedback regulated by several mitotic kinases. These kinases are reactivated from checkpoint arrest to deactivate the checkpoint and restart cell cycle progression, thereby allowing the cell to recover from the DNA damage checkpoint. The emerging role of mitotic kinases in the DNA damage pathway provides important insights into cancer progression and treatment. PMID:23618492

  9. A Centromere-Signaling Network Underlies the Coordination among Mitotic Events.

    PubMed

    Trivedi, Prasad; Stukenberg, P Todd

    2016-02-01

    There is increasing evidence that regulators of the spindle checkpoint, kinetochore-microtubule attachments, and sister chromatid cohesion are part of an interconnected mitotic regulatory circuit with two positive feedback loops and the chromosome passenger complex (CPC) at its center. If true, this conceptual breakthrough needs to be integrated into models of mitosis. In this review, we describe this circuit and point out how the double feedback loops could provide insights into the self-organization of some mitotic processes and the autonomy of every chromosome on the mitotic spindle. We also provide working models for how mitotic events may be coordinated by this circuit. PMID:26705896

  10. Cascaded ensemble of convolutional neural networks and handcrafted features for mitosis detection

    NASA Astrophysics Data System (ADS)

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-03-01

    Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is mitotic count, which involves quantifying the number of cells in the process of dividing (i.e. undergoing mitosis) at a specific point in time. Currently mitosis counting is done manually by a pathologist looking at multiple high power fields on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical or textural attributes of mitoses or features learned with convolutional neural networks (CNN). While handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely unsupervised feature generation methods, there is an appeal to attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. In this paper, we present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 High Power Fields (HPF, x400 magnification) by several pathologists and 15 testing HPFs yielded an F-measure of 0.7345. Apart from this being the second best performance ever recorded for this MITOS dataset, our approach is faster and requires fewer computing resources compared to extant methods, making this feasible for clinical use.

  11. Development of a computational high-throughput tool for the quantitative examination of dose-dependent histological features.

    PubMed

    Nault, Rance; Colbry, Dirk; Brandenberger, Christina; Harkema, Jack R; Zacharewski, Timothy R

    2015-04-01

    High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT validation was demonstrated by comparison with manual quantitation using liver sections from mice orally gavaged with sesame oil vehicle or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.001-30 μg/kg) every 4 days for 28 days, which elicits hepatic steatosis with mild fibrosis. A quality control module of QuHAnT reduced the number of quantifiable Oil Red O (ORO)-stained images from 3,123 to 2,756. Increased ORO staining was measured at 10 and 30 μg/kg TCDD with a high correlation between manual and computational volume densities (Vv ), although the dynamic range of QuHAnT was 10-fold greater. Additionally, QuHAnT determined the size of each ORO vacuole, which could not be accurately quantitated by visual examination or manual point counting. PicroSirius Red quantitation demonstrated superior collagen deposition detection due to the ability to consider all images within each section. QuHAnT dramatically reduced analysis time and facilitated the comprehensive assessment of features improving accuracy and sensitivity and represents a complementary tool for tissue/cellular features that are difficult and tedious to assess via subjective or semiquantitative methods. PMID:25274660

  12. The Luminous Polycyclic Aromatic Hydrocarbon Emission Features: Applications to High Redshift Galaxies and Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Shipley, Heath V.

    2016-01-01

    For decades, significant work has been applied to calibrating emission from the ultra-violet, nebular emission lines, far-infrared, X-ray and radio as tracers of the star-formation rate (SFR) in distant galaxies. Understanding the exact rate of star-formation and how it evolves with time and galaxy mass has deep implications for how galaxies form. The co-evolution of star-formation and supermassive black hole (SMBH) accretion is one of the key problems in galaxy formation theory. But, many of these SFR indicators are influenced by SMBH accretion in galaxies and result in unreliable SFRs. Utilizing the luminous polycyclic aromatic hydrocarbon (PAH) emission features, I provide a new robust SFR calibration using the luminosity emitted from the PAHs at 6.2?m, 7.7?m and 11.3?m to solve this. The PAH features emit strongly in the mid-infrared (mid-IR; 5-25?m) mitigating dust extinction, containing on average 5-10% of the total IR luminosity in galaxies. I use a sample of 105 star-forming galaxies covering a range of total IR luminosity, LIR = L(8-1000?m) = 109 - 1012 L? and redshift 0 < z < 0.4, with mid-IR spectroscopy from the Spitzer Infrared Spectrograph (IRS), and data covering other SFR indicators (H? emission and rest-frame 24?m continuum emission). The PAH luminosity correlates linearly with the SFR as measured by the H? luminosity (corrected for attenuation using the mono-chromatic rest-frame 24?m emission), with a tight scatter of <0.15 dex. The scatter is comparable to that between SFRs derived from the Pa? and dust-corrected H? emission lines. We present a case study in advance of JWST, which will be capable of measuring SFRs (from 8?m rest-frame photometry, i.e. PAHs) in distant galaxies (z ? 2) with JWST/MIRI to SFRs as low as ~10 M?yr-1, because the PAH features are so bright. We use Spitzer/IRS observations of PAH features in lensed star-forming galaxies at 1 < z < 3 to demonstrate the utility of the PAHs to derive SFRs that agree with those available from Pa?. This new SFR indicator will be useful for probing the peak of the SFR density in the universe (1 < z < 3) and for studying the co-evolution of star-formation and supermassive blackhole accretion contemporaneously in a galaxy.

  13. 2-Methoxyestradiol Induces Mitotic Arrest, Apoptosis, and Synergistic Cytotoxicity with Arsenic Trioxide in Human Urothelial Carcinoma Cells

    PubMed Central

    Ho, I-Lin; Chang, Hong-Chiang; Lee, Ping-Yi; Chung, Yuan-Ting; Hsieh, Ju-Ton; Pu, Yeong-Shiau; Shi, Chung-Sheng; Huang, Kuo-How

    2013-01-01

    2-Methoxyestradiol (2-ME), an endogenous derivative of 17?-estradiol, has been reported to elicit antiproliferative responses in various tumors. In this study, we investigated the effects of 2-ME on cell viability, proliferation, cell cycle, and apoptosis in human urothelial carcinoma (UC) cell lines. We used two high-grade human bladder UC cell lines (NTUB1 and T24). After treatment with 2-ME, the cell viability and apoptosis were measured by MTT assay and flow cytometry (fluorescence-activated cell sorting), with annexin V-FITC staining and propidium iodide (PI) labeling. DNA fragmentation was analyzed by agarose gel electrophoresis. Flow cytometry with PI labeling was used for the cell cycle analyses. The protein levels of caspase activations, poly (ADP-ribose) polymerase (PARP) cleavage, phospho-histone H2A.X, phospho-Bad, and cell cycle regulatory molecules were measured by Western blot. The effects of the drug combinations were analyzed using the computer software, CalcuSyn. We demonstrated that 2-ME effectively induces dose-dependent cytotoxicity and apoptosis in human UC cells after 24 h exposure. DNA fragmentation, PARP cleavage, and caspase-3, 7, 8, 9 activations can be observed with 2-ME-induced apoptosis. The decreased phospho-Bad (Ser136 and Ser155) and mitotic arrest of the cell cycle in the process of apoptosis after 2-ME treatment was remarkable. In response to mitotic arrest, the mitotic forms of cdc25C, phospho-cdc2, cyclin B1, and phospho-histone H3 (Ser10) were activated. In combination with arsenic trioxide (As2O3), 2-ME elicited synergistic cytotoxicity (combination index <1) in UC cells. We concluded that 2-ME significantly induces apoptosis through decreased phospho-Bad and arrests bladder UC cells at the mitotic phase. The synergistic antitumor effect with As2O3 provides a novel implication in clinical treatment of UC. PMID:23967052

  14. Cyclin-dependent kinase 1 inhibitor RO3306 promotes mitotic slippage in paclitaxel-treated HepG2 cells.

    PubMed

    Xiao, J; Qiu, P; Lai, X; He, P; Wu, Y; Du, B; Tan, Y

    2013-09-20

    Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and current systemic chemotherapy are mostly ineffective. Paclitaxel (PTX) has a?clinically significant effect on many malignant tumors. Cells treated with PTX undergo reversible mitotic arrest and although high doses can cause side effects it may also induce apoptosis. We investigated the effect of a?sequential combination of PTX and RO3306, a?cyclin-dependent kinase 1 inhibitor, on the hepatocellular carcinoma HepG2 cell line. The sequential drug treatment protocol involved the addition of PTX (0.2 mol/L) for 18 h?followed by RO3306 (2 mol/L) for a?further 6 h. Cell viability and proliferation were measured using tetrazolium dye (MTT) and colony formation assay. Cell cycle profiles were established by flow cytometry. The expression level of protein was examined by immunoblotting. We observed a?synergistic effect of PTX and RO3306 treatment on cell growth and proliferation as well as an increased proportion of cells in sub-G1 phase. Expression levels of cyclin B, cyclin E?and phosphorylated Histone H3 demonstrated that RO3306 enhanced apoptosis in PTX treated cells by mitotic slippage. Our data suggested that the combination of PTX and RO3306 may be an effective therapeutic combination for the treatment of liver cancer. Keywords: paclitaxel; RO3306; apoptosis; mitotic slippage; HepG2 cells. PMID:24050548

  15. Intraventricular pleomorphic xanthoastrocytoma with anaplastic features.

    PubMed

    Fu, Yong-Juan; Miyahara, Hiroaki; Uzuka, Takeo; Natsumeda, Manabu; Okamoto, Kouichirou; Hirose, Takanori; Fujii, Yukihiko; Takahashi, Hitoshi

    2010-08-01

    Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor that usually occurs in the superficial cerebral hemispheres of children and young adults and has a relatively favorable prognosis. We report an unusual case of supratentorial, intraventricular tumor in a 52-year-old man. The tumor was composed of pleomorphic cells, including giant cells, most of which were multinucleated, and small cells. In addition, frequent xanthic changes in the cytoplasm of the tumor cells, and widespread reticulin deposits and lymphocytic infiltrates in the stroma were characteristic features. Large areas of necrosis were also evident. However, mitotic figures were rare (1-2 mitoses per 10 high-power fields). Many tumor cells were positive for GFAP, and a number were positive for neurofilament protein and synaptophysin, indicating their neuronal differentiation. In addition, occasional tumor cells were positive for CD34. p53 protein was entirely negative in the tumor cells. In diagnosing this tumor histopathologically, differentiation between PXA and giant cell glioblastoma (GCG), a rare variant of glioblastoma, was problematic. However, considering the overall histopathological picture, a final diagnosis of PXA with anaplastic features was made. The present case indicates that PXA can occur as an intraventricular tumor, and suggests that in some instances, it would be very difficult to differentiate PXA and GCG histopathologically. PMID:20051018

  16. The luminous polycyclic aromatic hydrocarbon emission features: Applications to high redshift galaxies and active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Shipley, Heath Vernon

    The co-evolution of star-formation and supermassive black hole (SMBH) accretion in galaxies is one of the key problems in galaxy formation theory. Understanding the formation of galaxies, and their subsequent evolution, will be coupled to intensive study of the evolution of SMBHs. This thesis focuses on studying diagnostics of star-formation and SMBH accretion to develop tools to study this co-evolution. Chapter 2 consists of using mid-infrared (mid-IR) spectroscopy from the Spitzer Infrared Spectrograph (IRS) to study the nature of star-formation and SMBH accretion. The mid-IR spectra cover wavelengths 5-38mum, spanning the polycyclic aromatic hydrocarbon (PAH) features and important atomic diagnostic lines. We divide our sample into a subsample of galaxies with Spitzer IRAC colors indicative of warm dust heated by an AGN (IRAGN) and those galaxies whose colors indicate star-formation processes (non-IRAGN). In both the IRAGN and star-forming samples, the luminosity in the PAH features correlates strongly with [Ne II]lambda12.8&mum emission line, from which we conclude that the PAH luminosity directly traces the instantaneous star-formation rate (SFR) in both the IRAGN and star-forming galaxies. There is no measurable difference between the PAH luminosity ratios of L11:3/L7:7 and L6:2/L7:7 for the IRAGN and non-IRAGN, suggesting that AGN do not significantly excite or destroy PAH molecules on galaxy-wide scales. In chapter 3, I calibrate the PAH luminosity as a SFR indicator. We provide a new robust SFR calibration using the luminosity emitted from PAH molecules at 6.2mum, 7.7mum and 11.3mum. The PAH features emit strongly in the mid-IR mitigating dust extinction, containing on average 5--10% of the total IR luminosity in galaxies. We use mid-IR spectroscopy from the Spitzer/IRS, and data covering other SFR indicators (Halpha emission and rest-frame 24mum continuum emission). The PAH luminosity correlates linearly with the SFR as measured by the Halpha luminosity (corrected for attenuation using the mono-chromatic rest-frame 24um emission), with a tight scatter of 0.15 dex. The scatter is comparable to that between SFRs derived from the Paalpha and dust-corrected Halpha emission lines, implying the PAH features may be as accurate a SFR indicator as the Hydrogen recombination lines. Because the PAH features are so bright, our PAH SFR calibration enables an efficient way to measure SFRs in distant galaxies with JWST to SFRs as low as ~10 M; yr-1 to z >~ 2. We use Spitzer/IRS observations of PAH features in lensed star-forming galaxies at 1 < z < 3 to demonstrate the utility of the PAHs to derive SFRs as accurate as those available from Paalpha. Chapter 4 is the application of the PAH SFRs for galaxies with AGN to demonstrate the reliability for studies of the co-evolution of star-formation and SMBH accretion. We present a study of the contribution from star-formation in galaxies of varying AGN activity (from pure star-forming galaxies to quasars) as a function of total IR luminosity using a sample of 220 galaxies. We use mid-IR spectroscopy from the Spitzer/IRS and photometry from the MIPS mum, 70mum and 160mum bands with partial coverage of the sample with the Herschel 160mum band for the quasars. The contribution from star-formation to the total IR luminosity implied by the PAH emission decreases with increasing IR luminosity. We find a similar result to previous studies for the correlation between SFR, i.e. PAH luminosity, and AGN luminosity for quasars of LSF [special characters omitted] for the 11.3mum PAH feature only (which has been shown to be the most reliable PAH feature in the vicinity of AGN). This may indicate the PAH luminosity remains a reliable tracer of the SFR for galaxies with strong AGN contributions (i.e. quasars), as we did not subtract off the AGN component before measuring the SFR from the PAH luminosity.

  17. Asynchronous Event-Based Multikernel Algorithm for High-Speed Visual Features Tracking.

    PubMed

    Lagorce, Xavier; Meyer, Cdric; Ieng, Sio-Hoi; Filliat, David; Benosman, Ryad

    2015-08-01

    This paper presents a number of new methods for visual tracking using the output of an event-based asynchronous neuromorphic dynamic vision sensor. It allows the tracking of multiple visual features in real time, achieving an update rate of several hundred kilohertz on a standard desktop PC. The approach has been specially adapted to take advantage of the event-driven properties of these sensors by combining both spatial and temporal correlations of events in an asynchronous iterative framework. Various kernels, such as Gaussian, Gabor, combinations of Gabor functions, and arbitrary user-defined kernels, are used to track features from incoming events. The trackers described in this paper are capable of handling variations in position, scale, and orientation through the use of multiple pools of trackers. This approach avoids the N(2) operations per event associated with conventional kernel-based convolution operations with N N kernels. The tracking performance was evaluated experimentally for each type of kernel in order to demonstrate the robustness of the proposed solution. PMID:25248193

  18. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features.

    PubMed

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-10-01

    Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 HPFs ([Formula: see text] magnification) by several pathologists and 15 testing HPFs yielded an [Formula: see text]-measure of 0.7345. Our approach is accurate, fast, and requires fewer computing resources compared to existent methods, making this feasible for clinical use. PMID:26158062

  19. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features

    PubMed Central

    Wang, Haibo; Cruz-Roa, Angel; Basavanhally, Ajay; Gilmore, Hannah; Shih, Natalie; Feldman, Mike; Tomaszewski, John; Gonzalez, Fabio; Madabhushi, Anant

    2014-01-01

    Abstract. Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 HPFs (400× magnification) by several pathologists and 15 testing HPFs yielded an F-measure of 0.7345. Our approach is accurate, fast, and requires fewer computing resources compared to existent methods, making this feasible for clinical use. PMID:26158062

  20. Mitotic indirect non-disjunction in phytohemagglutinin stimulated human lymphocytes.

    PubMed

    Gustavino, B; Degrassi, F; Filipponi, R; Modesti, D; Tanzarella, C; Rizzoni, M

    1994-01-01

    In a previous publication we demonstrated that in cells of Vicia faba micronuclei derived from whole lagging chromosomes or chromatids may perform DNA synthesis and mitotic condensation in synchrony with main nuclei and be regained by main nuclei at the next mitosis, giving rise to trisomic cells together with diploids. This process was called 'mitotic indirect non-disjunction' (MIND). In the present work the occurrence of MIND was studied in human lymphocytes cultivated in vitro. Human lymphocytes were treated with low colcemid concentrations until fixation; BrUdR was supplied together with colcemid to distinguish the number of mitoses performed by the cells (M1, M2 and M3 cells). The frequencies of M1 ana-telophases with single lagging chromosomes/chromatids and of M2+ prophases with single micronuclei in synchronous motitic condensation with main nuclei were evaluated. On this basis the expected frequencies of both monosomic and trisomic M2 cells were calculated, according to the hypothesis of MIND. Their observed frequencies were very close to those expected. These results support the hypothesis of the occurrence of MIND in human lymphocytes. PMID:8208126

  1. A molecular mechanism of mitotic centrosome assembly in Drosophila

    PubMed Central

    Conduit, Paul T; Richens, Jennifer H; Wainman, Alan; Holder, James; Vicente, Catarina C; Pratt, Metta B; Dix, Carly I; Novak, Zsofia A; Dobbie, Ian M; Schermelleh, Lothar; Raff, Jordan W

    2014-01-01

    Centrosomes comprise a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, but it is unclear how this occurs. In this study, we show that the centriole protein Asl initiates the recruitment of DSpd-2 and Cnn to mother centrioles; both proteins then assemble into co-dependent scaffold-like structures that spread outwards from the mother centriole and recruit most, if not all, other PCM components. In the absence of either DSpd-2 or Cnn, mitotic PCM assembly is diminished; in the absence of both proteins, it appears to be abolished. We show that DSpd-2 helps incorporate Cnn into the PCM and that Cnn then helps maintain DSpd-2 within the PCM, creating a positive feedback loop that promotes robust PCM expansion around the mother centriole during mitosis. These observations suggest a surprisingly simple mechanism of mitotic PCM assembly in flies. DOI: http://dx.doi.org/10.7554/eLife.03399.001 PMID:25149451

  2. Endogenous localizome identifies 43 mitotic kinesins in a plant cell

    PubMed Central

    Miki, Tomohiro; Naito, Haruko; Nishina, Momoko; Goshima, Gohta

    2014-01-01

    Kinesins are microtubule (MT)-based motor proteins that have been identified in every eukaryotic species. Intriguingly, land plants have more than 60 kinesins in their genomes, many more than that in yeasts or animals. However, many of these have not yet been characterized, and their cellular functions are unknown. Here, by using endogenous tagging, we comprehensively determined the localization of 72 kinesins during mitosis in the moss Physcomitrella patens. We found that 43 kinesins are localized to mitotic structures such as kinetochores, spindle MTs, or phragmoplasts, which are MT-based structures formed during cytokinesis. Surprisingly, only one of them showed an identical localization pattern to the animal homolog, and many were enriched at unexpected sites. RNA interference and live-cell microscopy revealed postanaphase roles for kinesin-5 in spindle/phragmoplast organization, chromosome segregation, and cytokinesis, which have not been observed in animals. Our study thus provides a list of MT-based motor proteins associated with the cell division machinery in plants. Furthermore, our data challenge the current generalization of determining mitotic kinesin function based solely on studies using yeast and animal cells. PMID:24591632

  3. Mitotic Internalization of Planar Cell Polarity Proteins Preserves Tissue Polarity

    PubMed Central

    Devenport, Danelle; Oristian, Daniel; Heller, Evan; Fuchs, Elaine

    2011-01-01

    Planar cell polarity (PCP) is the collective polarization of cells along the epithelial plane, a process best understood in the terminally differentiated Drosophila wing. Proliferative tissues such as mammalian skin also display PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically-distributed PCP components risk mislocalisation or unequal inheritance, which could have profound consequences on the long-range propagation of polarity. Here, we show that when mouse epidermal basal progenitors divide, PCP components are selectively internalized into endosomes, which are inherited equally by daughter cells. Following mitosis, PCP proteins are recycled to the cell surface where asymmetry is re-established by a process reliant upon neighbouring PCP. A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot mitotically internalize, exhibit perturbed hair follicle angling, a hallmark of defective PCP. This underscores the physiological relevance and importance of this novel mechanism for regulating polarity during cell division. PMID:21743464

  4. Evidence for mitotic recombination in W sup ei /+ heterozygous mice

    SciTech Connect

    Panthier, J.J.; Condamine, H.; Jacob, F. ); Guenet, J.L. )

    1990-05-01

    A number of alleles at coat color loci of the house mouse give rise to areas of wild-type pigmentation on the coats of otherwise mutant animals. Such unstable alleles include both recessive and dominant mutations. Among the latter are several alleles at the W locus. In this report, phenotypic reversions of the W{sup ei} allele at the W locus were studied. Mice heterozygous in repulsion for both W{sup ei} and buff (bf) (i.e. W{sup ei}+/+bf) were examined for the occurrence of phenotypic reversion events. Buff (bf) is a recessive mutation, which lies 21 cM from W on the telomeric side of chromosome 5 and is responsible for the khaki colored coat of nonagouti buff homozygotes (a/a; bf/bf). Two kinds of fully pigmented reversion spots were recovered on the coats of a/a; W{sup ei}+/+bf mice: either solid black or khaki colored. Furthermore phenotypic reversions of W{sup ei}/+ were enhanced significantly following X-irradiation of 9.25-day-old W{sup ei}/+ embryos (P < 0.04). These observations are consistent with the suggestion of a role for mitotic recombination in the origin of these phenotypic reversions. In addition these results raise the intriguing possibility that some W mutations may enhance mitotic recombination in the house mouse.

  5. Analysis and modeling of mitotic spindle orientations in three dimensions

    PubMed Central

    Jschke, Christoph; Xie, Yunli; Postiglione, Maria Pia; Knoblich, Juergen A.

    2014-01-01

    The orientation of the mitotic spindle determines the relative size and position of the daughter cells and influences the asymmetric inheritance of localized cell fate determinants. The onset of mammalian neurogenesis, for example, coincides with changes in spindle orientation. To address the functional implications of this and related phenomena, precise methods for determining the orientation of the mitotic spindle in complex tissues are needed. Here, we present methodology for the analysis of spindle orientation in 3D. Our method allows statistical analysis and modeling of spindle orientation and involves two parameters for horizontal and vertical bias that can unambiguously describe the distribution of spindle orientations in an experimental sample. We find that 3D analysis leads to systematically different results from 2D analysis and, surprisingly, truly random spindle orientations do not result in equal numbers of horizontal and vertical orientations. We show that our method can describe the distribution of spindle orientation angles under different biological conditions. As an example of biological application we demonstrate that the adapter protein Inscuteable (mInsc) can actively promote vertical spindle orientation in apical progenitors during mouse neurogenesis. PMID:24381158

  6. Inhibition of mitotic-specific histone phophorylation by sodium arsenite

    SciTech Connect

    Cobo, J.M.; Valdez, J.G.; Gurley, L.R.

    1994-10-01

    Synchronized cultures of Chinese hamster cells (line CHO) were used to measure the effects of 10{mu}M sodium arsenite on histone phosphorylation. This treatment caused cell proliferation to be temporarily arrested, after which the cells spontaneously resumed cell proliferation in a radiomimetric manner. Immediately following treatment, it was found that sodium arsenite affected only mitotic-specific HI and H3 phosphorylations. Neither interphase, nor mitotic, H2A and H4 phosphorylations were affected, nor was interphase HI Phosphorylation affected. The phosphorylation of HI was inhibited only in mitosis, reducing HI phosphorylation to 38.1% of control levels, which was the level of interphase HI phosphorylation. The phosphorylation of both H3 variants was inhibited in mitosis, the less hydrophobic H3 to 19% and the more hydrophobic H3 to 24% of control levels. These results suggest that sodium arsenite may inhibite cell proliferation by interfering with the cyclin B/p34{sup cdc2} histone kinase activity which is thought to play a key role in regulating the cell cycle. It has been proposed by our laboratory that HI and H3 phosphorylations play a role in restructuring interphase chromatin into metaphase chromosomes. Interference of this process by sodium arsenite may lead to structurally damaged chromosomes resulting in the increased cancer risks known to be produced by arsenic exposure from the environment.

  7. A Genome Scale Screen for Mutants with Delayed Exit from Mitosis: Ire1-Independent Induction of Autophagy Integrates ER Homeostasis into Mitotic Lifespan

    PubMed Central

    Ghavidel, Ata; Baxi, Kunal; Ignatchenko, Vladimir; Prusinkiewicz, Martin; Arnason, Terra G.; Kislinger, Thomas; Carvalho, Carlos E.; Harkness, Troy A. A.

    2015-01-01

    Proliferating eukaryotic cells undergo a finite number of cell divisions before irreversibly exiting mitosis. Yet pathways that normally limit the number of cell divisions remain poorly characterized. Here we describe a screen of a collection of 3762 single gene mutants in the yeast Saccharomyces cerevisiae, accounting for 2/3 of annotated yeast ORFs, to search for mutants that undergo an atypically high number of cell divisions. Many of the potential longevity genes map to cellular processes not previously implicated in mitotic senescence, suggesting that regulatory mechanisms governing mitotic exit may be broader than currently anticipated. We focused on an ER-Golgi gene cluster isolated in this screen to determine how these ubiquitous organelles integrate into mitotic longevity. We report that a chronic increase in ER protein load signals an expansion in the assembly of autophagosomes in an Ire1-independent manner, accelerates trafficking of high molecular weight protein aggregates from the cytoplasm to the vacuoles, and leads to a profound enhancement of daughter cell production. We demonstrate that this catabolic network is evolutionarily conserved, as it also extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data provide evidence that catabolism of protein aggregates, a natural byproduct of high protein synthesis and turn over in dividing cells, is among the drivers of mitotic longevity in eukaryotes. PMID:26247883

  8. Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells.

    PubMed

    Zhang, Yuanyuan; Wang, Yuqi; Wei, Youheng; Wu, Jiaxue; Zhang, Pingzhao; Shen, Suqin; Saiyin, Hexige; Wumaier, Reziya; Yang, Xianmei; Wang, Chenji; Yu, Long

    2016-03-01

    CCT3 was one of the subunits of molecular chaperone CCT/TRiC complex, which plays a central role in maintaining cellular proteostasis. We demonstrated that expressions of CCT3 mRNA and protein are highly up-regulated in hepatocellular carcinoma (HCC) tissues, and high level of CCT3 is correlated with poor survival in cancer patients. In HCC cell lines, CCT3 depletion suppresses cell proliferation by inducing mitotic arrest at prometaphase and apoptosis eventually. We also identified CCT3 as a novel regulator of spindle integrity and as a requirement for proper kinetochore-microtubule attachment during mitosis. Moreover, we found that CCT3 depletion sensitizes HCC cells to microtubule destabilizing drug Vincristine. Collectively, our study suggests that CCT3 is indispensible for HCC cell proliferation, and provides a potential drug target for treatment of HCC. PMID:26739059

  9. Special features of high-speed interaction of supercavitating solids in water

    NASA Astrophysics Data System (ADS)

    Ishchenko, Aleksandr; Akinshin, Ruslan; Afanas'eva, Svetlana; Borisenkov, Igor; Burkin, Viktor; Diachkovskii, Aleksei; Korolkov, Leonid; Moiseev, Dmitrii; Khabibullin, Marat

    2016-01-01

    Special features of material behavior of a supercavitating projectile are investigated at various initial velocities of entering water on the basis of the developed stress-strain state model with possibility of destruction of solids when moving in water and interacting with various underwater barriers with the use of consistent methodological approach of mechanics of continuous media. The calculation-experimental method was used to study the modes of motion of supercavitating projectiles at sub- and supersonic velocities in water medium after acceleration in the barrelled accelerator, as well as their interaction with barriers. Issues of stabilization of the supercavitating projectile on the initial flight path in water were studied. Microphotographs of state of solids made of various materials, before and after interaction with water, at subsonic and supersonic velocities were presented. Supersonic velocity of the supercavitating projectile motion in water of 1590 m/s was recorded.

  10. Edge detection of street trees in high-resolution remote sensing images using spectrum features

    NASA Astrophysics Data System (ADS)

    Zhao, Haohao; Xiao, Pengfeng; Feng, Xuezhi

    2013-10-01

    In this paper a method of Fourier spectrum features based edge detection of urban street trees is described. The QuickBird image was first transformed by 2-D discrete Fourier transform. Then the energy of the component in spatial frequency was calculated. The energy distribution of the angle in max energy was used for further study. Different frequency segments was analyzed, the frequency that can best describe the street tree edge was chosen as the cut-off frequency of the street trees edge. Odd Gabor filter in frequency domain with the cut-off frequency and the max-energy angle was applied for the edge detection. The road center line is extracted by a Gabor filter in frequency domain. Then the edge of the street trees is restricted by the road center line. The edge detection result is analyzed by Canny criteria, and the ?V=1.00, and C=0.89.

  11. High performance organic integrated device with ultraviolet photodetective and electroluminescent properties consisting of a charge-transfer-featured naphthalimide derivative

    NASA Astrophysics Data System (ADS)

    Wang, Hanyu; Zhou, Jie; Wang, Xu; Lu, Zhiyun; Yu, Junsheng

    2014-08-01

    A high performance organic integrated device (OID) with ultraviolet photodetective and electroluminescent (EL) properties was fabricated by using a charge-transfer-featured naphthalimide derivative of 6-{3,5-bis-[9-(4-t-butylphenyl)-9H-carbazol-3-yl]-phenoxy}-2-(4-t-butylphenyl)-benzo[de]isoquinoline-1,3-dione (CzPhONI) as the active layer. The results showed that the OID had a high detectivity of 1.5 1011 Jones at -3 V under the UV-350 nm illumination with an intensity of 0.6 mW/cm2, and yielded an exciplex EL light emission with a maximum brightness of 1437 cd/m2. Based on the energy band diagram, both the charge transfer feature of CzPhONI and matched energy level alignment were responsible for the dual ultraviolet photodetective and EL functions of OID.

  12. Rabbit System. Low cost, high reliability front end electronics featuring 16 bit dynamic range. [Redundant Analog Bus Based Information Transfer

    SciTech Connect

    Drake, G.; Droege, T.F.; Nelson, C.A. Jr.; Turner, K.J.; Ohska, T.K.

    1985-10-01

    A new crate-based front end system has been built which features low cost, compact packaging, command capability, 16 bit dynamic range digitization, and a high degree of redundancy. The crate can contain a variety of instrumentation modules, and is designed to be situated close to the detector. The system is suitable for readout of a large number of channels via parallel multiprocessor data acquisition.

  13. High-resolution multibeam mapping and submersible surveys of topographic features in the northwestern Gulf of Mexico

    USGS Publications Warehouse

    Hickerson, E.L.; Schmahl, G.P.; Weaver, D.C.; Gardner, J.V.

    2003-01-01

    The Flower Garden Banks National Marine Sanctuary (FGBNMS) and the USGS Pacific Seafloor Mapping Project mapped about 2000 km2 of the northwestern Gulf of Mexico continental shelf during June 2002, using a Kongsberg Simrad EM1000 multibeam echosounder. Mapping focused on select topographic highs thave hae been idetnnfied as biological features warranting protection from oil and gas activities by the Minerals Management Service (MMS). The base maps will be used for all future ROV and submersible missions.

  14. Very high resolution Earth observation features for monitoring plant and animal community structure across multiple spatial scales in protected areas

    NASA Astrophysics Data System (ADS)

    Mairota, Paola; Cafarelli, Barbara; Labadessa, Rocco; Lovergine, Francesco; Tarantino, Cristina; Lucas, Richard M.; Nagendra, Harini; Didham, Raphael K.

    2015-05-01

    Monitoring the status and future trends in biodiversity can be prohibitively expensive using ground-based surveys. Consequently, significant effort is being invested in the use of satellite remote sensing to represent aspects of the proximate mechanisms (e.g., resource availability) that can be related to biodiversity surrogates (BS) such as species community descriptors. We explored the potential of very high resolution (VHR) satellite Earth observation (EO) features as proxies for habitat structural attributes that influence spatial variation in habitat quality and biodiversity change. In a semi-natural grassland mosaic of conservation concern in southern Italy, we employed a hierarchical nested sampling strategy to collect field and VHR-EO data across three spatial extent levels (landscape, patch and plot). Species incidence and abundance data were collected at the plot level for plant, insect and bird functional groups. Spectral and textural VHR-EO image features were derived from a Worldview-2 image. Three window sizes (grains) were tested for analysis and computation of textural features, guided by the perception limits of different organisms. The modelled relationships between VHR-EO features and BS responses differed across scales, suggesting that landscape, patch and plot levels are respectively most appropriate when dealing with birds, plants and insects. This research demonstrates the potential of VHR-EO for biodiversity mapping and habitat modelling, and highlights the importance of identifying the appropriate scale of analysis for specific taxonomic groups of interest. Further, textural features are important in the modelling of functional group-specific indices which represent BS in high conservation value habitat types, and provide a more direct link to species interaction networks and ecosystem functioning, than provided by traditional taxonomic diversity indices.

  15. Mitotic catastrophe and cancer drug resistance: A link that must to be broken.

    PubMed

    Denisenko, Tatiana V; Sorokina, Irina V; Gogvadze, Vladimir; Zhivotovsky, Boris

    2016-01-01

    An increased tendency of genomic alterations during the life cycle of cells leads to genomic instability, which is a major driving force for tumorigenesis. A considerable fraction of tumor cells are tetraploid or aneuploid, which renders them intrinsically susceptible to mitotic aberrations, and hence, are particularly sensitive to the induction of mitotic catastrophe. Resistance to cell death is also closely linked to genomic instability, as it enables malignant cells to expand even in a stressful environment. Currently it is known that cells can die via multiple mechanisms. Mitotic catastrophe represents a step preceding apoptosis or necrosis, depending on the expression and/or proper function of several proteins. Mitotic catastrophe was proposed to be an onco-suppressive mechanism and the evasion of mitotic catastrophe constitutes one of the gateways to cancer development. Thus, stimulation of mitotic catastrophe appears to be a promising strategy in cancer treatment. Indeed, several chemotherapeutic drugs are currently used at concentrations that induce apoptosis irrespective of the cell cycle phase, yet are very efficient at triggering mitotic catastrophe at lower doses, significantly limiting side effects. In the present review we summarize current data concerning the role of mitotic catastrophe in cancer drug resistance and discuss novel strategies to break this link. PMID:26830311

  16. Gamma-actin is involved in regulating centrosome function and mitotic progression in cancer cells.

    PubMed

    Po'uha, Sela T; Kavallaris, Maria

    2015-12-17

    Reorganization of the actin cytoskeleton during mitosis is crucial for regulating cell division. A functional role for ?-actin in mitotic arrest induced by the microtubule-targeted agent, paclitaxel, has recently been demonstrated. We hypothesized that ?-actin plays a role in mitosis. Herein, we investigated the effect of ?-actin in mitosis and demonstrated that ?-actin is important in the distribution of ?-actin and formation of actin-rich retraction fibers during mitosis. The reduced ability of paclitaxel to induce mitotic arrest as a result of ?-actin depletion was replicated with a range of mitotic inhibitors, suggesting that ?-actin loss reduces the ability of broad classes of anti-mitotic agents to induce mitotic arrest. In addition, partial depletion of ?-actin enhanced centrosome amplification in cancer cells and caused a significant delay in prometaphase/metaphase. This prolonged prometaphase/metaphase arrest was due to mitotic defects such as uncongressed and missegregated chromosomes, and correlated with an increased presence of mitotic spindle abnormalities in the ?-actin depleted cells. Collectively, these results demonstrate a previously unknown role for ?-actin in regulating centrosome function, chromosome alignment and maintenance of mitotic spindle integrity. PMID:26697841

  17. DEVELOPING PHYLOGENIES FOR INTEGRATING MITOTIC FUNGI IN THE HYPOCREALES AND DIAPORTHALES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent comprehensive studies of the Hypocreales and Diaporthales using both morphological and molecular characters present the opportunity to integrate the mitotic fungi and to evaluate character evolution of both teleomorphic and anamorphic states. The majority of plant-associated fungi are mitotic...

  18. Identification of the oncogenic kinase TOPK/PBK as a master mitotic regulator of C2H2 zinc finger proteins.

    PubMed

    Rizkallah, Raed; Batsomboon, Paratchata; Dudley, Gregory B; Hurt, Myra M

    2015-01-30

    TOPK/PBK is an oncogenic kinase upregulated in most human cancers and its high expression correlates with poor prognosis. TOPK is known to be activated by Cdk1 and needed for mitotic cell division; however, its mitotic functions are not yet fully understood. In this study, we show that TOPK plays a global mitotic role by simultaneously regulating hundreds of DNA binding proteins. C2H2 zinc finger proteins (ZFPs) constitute the largest family of human proteins. All C2H2 ZFPs contain a highly conserved linker sequence joining their multi-zinc finger domains. We have previously shown that phosphorylation of this conserved motif serves as a global mechanism for the coordinate dissociation of C2H2 ZFPs from condensing chromatin, during mitosis. Here, using a panel of kinase inhibitors, we identified K252a as a potent inhibitor of mitotic ZFP linker phosphorylation. We generated a biotinylated form of K252a and used it to purify candidate kinases. From these candidates we identified TOPK/PBK, in vitro and in vivo, as the master ZFP linker kinase. Furthermore, we show precise temporal correlation between TOPK activating phosphorylation by Cdk1 and linker phosphorylation in mitosis. The identification of this fundamental role of TOPK underscores its significance as a promising novel target of cancer therapeutics. PMID:25575812

  19. High-order feature-based mixture models of classification learning predict individual learning curves and enable personalized teaching

    PubMed Central

    Cohen, Yarden; Schneidman, Elad

    2013-01-01

    Pattern classification learning tasks are commonly used to explore learning strategies in human subjects. The universal and individual traits of learning such tasks reflect our cognitive abilities and have been of interest both psychophysically and clinically. From a computational perspective, these tasks are hard, because the number of patterns and rules one could consider even in simple cases is exponentially large. Thus, when we learn to classify we must use simplifying assumptions and generalize. Studies of human behavior in probabilistic learning tasks have focused on rules in which pattern cues are independent, and also described individual behavior in terms of simple, single-cue, feature-based models. Here, we conducted psychophysical experiments in which people learned to classify binary sequences according to deterministic rules of different complexity, including high-order, multicue-dependent rules. We show that human performance on such tasks is very diverse, but that a class of reinforcement learning-like models that use a mixture of features captures individual learning behavior surprisingly well. These models reflect the important role of subjects priors, and their reliance on high-order features even when learning a low-order rule. Further, we show that these models predict future individual answers to a high degree of accuracy. We then use these models to build personally optimized teaching sessions and boost learning. PMID:23269833

  20. MOVING MAGNETIC FEATURES AROUND AR 10930 FROM HIGH-RESOLUTION DATA OBSERVED BY HINODE/SOT

    SciTech Connect

    Li Xiaobo; Zhang Hongqi

    2013-07-01

    We investigate the origin, configuration, and evolution of moving magnetic features (MMFs) in the moat and penumbra regions of NOAA AR 10930 using Hinode/SOT filtergrams and magnetograms. We differentiate MMFs into four types in terms of the location of first appearance and the source of initial flux. The main results are summed up as follows: (1) 50% of the MMFs are produced from or within the penumbra, while 50% are produced within the moat. The MMFs formed in the penumbra normally move outward along radial directions. The MMFs formed in the moat have more dispersed directions of motion. The average speed of most MMFs decreases radially. (2) About 63% of moat fluxes are input by flux emergences. Newly emerged MMFs are normally smaller in size. In their rise phase, they gain flux by adding newly emerging flux or merging other elements, and in the decline phase they lose flux by flux cancellation or fragmentation. The MMFs that are fragments separated from penumbra or other magnetic elements usually have larger flux and longer lifetime. They start their decay process once they are formed. Frequent merging and flux cancellation between MMFs are the dominant factors in MMFs' evolution. (3) Cancellations between opposite-polarity magnetic elements are responsible for most of the low chromospheric bright points. Bipole emergence and MMFs' severance from the penumbra also produce bright points. Elongated or horn-shaped micro-filaments may appear during the separation or cancellation process between magnetic elements.

  1. Applicability of data mining algorithms in the identification of beach features/patterns on high-resolution satellite data

    NASA Astrophysics Data System (ADS)

    Teodoro, Ana C.

    2015-01-01

    The available beach classification algorithms and sediment budget models are mainly based on in situ parameters, usually unavailable for several coastal areas. A morphological analysis using remotely sensed data is a valid alternative. This study focuses on the application of data mining techniques, particularly decision trees (DTs) and artificial neural networks (ANNs) to an IKONOS-2 image in order to identify beach features/patterns in a stretch of the northwest coast of Portugal. Based on knowledge of the coastal features, five classes were defined. In the identification of beach features/patterns, the ANN algorithm presented an overall accuracy of 98.6% and a kappa coefficient of 0.97. The best DTs algorithm (with pruning) presents an overall accuracy of 98.2% and a kappa coefficient of 0.97. The results obtained through the ANN and DTs were in agreement. However, the ANN presented a classification more sensitive to rip currents. The use of ANNs and DTs for beach classification from remotely sensed data resulted in an increased classification accuracy when compared with traditional classification methods. The association of remotely sensed high-spatial resolution data and data mining algorithms is an effective methodology with which to identify beach features/patterns.

  2. Preparing a cell for nuclear envelope breakdown: Spatio-temporal control of phosphorylation during mitotic entry.

    PubMed

    Alvarez-Fernndez, Mnica; Malumbres, Marcos

    2014-08-01

    Chromosome segregation requires the ordered separation of the newly replicated chromosomes between the two daughter cells. In most cells, this requires nuclear envelope (NE) disassembly during mitotic entry and its reformation at mitotic exit. Nuclear envelope breakdown (NEB) results in the mixture of two cellular compartments. This process is controlled through phosphorylation of multiple targets by cyclin-dependent kinase 1 (Cdk1)-cyclin B complexes as well as other mitotic enzymes. Experimental evidence also suggests that nucleo-cytoplasmic transport of critical cell cycle regulators such as Cdk1-cyclin B complexes or Greatwall, a kinase responsible for the inactivation of PP2A phosphatases, plays a major role in maintaining the boost of mitotic phosphorylation thus preventing the potential mitotic collapse derived from NEB. These data suggest the relevance of nucleo-cytoplasmic transport not only to communicate cytoplasmic and nuclear compartments during interphase, but also to prepare cells for the mixture of these two compartments during mitosis. PMID:24889070

  3. The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly.

    PubMed

    O'Brien, Lori L; Albee, Alison J; Liu, Lingling; Tao, Wei; Dobrzyn, Pawel; Lizarraga, Sofia B; Wiese, Christiane

    2005-06-01

    Maskin is the Xenopus homolog of the transforming acidic coiled coil (TACC)-family of microtubule and centrosome-interacting proteins. Members of this family share a approximately 200 amino acid coiled coil motif at their C-termini, but have only limited homology outside of this domain. In all species examined thus far, perturbations of TACC proteins lead to disruptions of cell cycle progression and/or embryonic lethality. In Drosophila, Caenorhabditis elegans, and humans, these disruptions have been attributed to mitotic spindle assembly defects, and the TACC proteins in these organisms are thought to function as structural components of the spindle. In contrast, cell division failure in early Xenopus embryo blastomeres has been attributed to a role of maskin in regulating the translation of, among others, cyclin B1 mRNA. In this study, we show that maskin, like other TACC proteins, plays a direct role in mitotic spindle assembly in Xenopus egg extracts and that this role is independent of cyclin B. Maskin immunodepletion and add-back experiments demonstrate that maskin, or a maskin-associated activity, is required for two distinct steps during spindle assembly in Xenopus egg extracts that can be distinguished by their response to "rescue" experiments. Defects in the "early" step, manifested by greatly reduced aster size during early time points in maskin-depleted extracts, can be rescued by readdition of purified full-length maskin. Moreover, defects in this step can also be rescued by addition of only the TACC-domain of maskin. In contrast, defects in the "late" step during spindle assembly, manifested by abnormal spindles at later time points, cannot be rescued by readdition of maskin. We show that maskin interacts with a number of proteins in egg extracts, including XMAP215, a known modulator of microtubule dynamics, and CPEB, a protein that is involved in translational regulation of important cell cycle regulators. Maskin depletion from egg extracts results in compromised microtubule asters and spindles and the mislocalization of XMAP215, but CPEB localization is unaffected. Together, these data suggest that in addition to its previously reported role as a translational regulator, maskin is also important for mitotic spindle assembly. PMID:15788567

  4. MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema.

    PubMed

    Manner, Johanna; Radlwimmer, Bernhard; Hohenberger, Peter; Mssinger, Katharina; Kffer, Stefan; Sauer, Christian; Belharazem, Djeda; Zettl, Andreas; Coindre, Jean-Michel; Hallermann, Christian; Hartmann, Jrg Thomas; Katenkamp, Detlef; Katenkamp, Kathrin; Schffski, Patrick; Sciot, Raf; Wozniak, Agnieszka; Lichter, Peter; Marx, Alexander; Strbel, Philipp

    2010-01-01

    Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC. This finding may have implications both for the diagnosis and treatment of these tumors. PMID:20008140

  5. MYC High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema

    PubMed Central

    Manner, Johanna; Radlwimmer, Bernhard; Hohenberger, Peter; Mssinger, Katharina; Kffer, Stefan; Sauer, Christian; Belharazem, Djeda; Zettl, Andreas; Coindre, Jean-Michel; Hallermann, Christian; Hartmann, Jrg Thomas; Katenkamp, Detlef; Katenkamp, Kathrin; Schffski, Patrick; Sciot, Raf; Wozniak, Agnieszka; Lichter, Peter; Marx, Alexander; Strbel, Philipp

    2010-01-01

    Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC. This finding may have implications both for the diagnosis and treatment of these tumors. PMID:20008140

  6. The Luminous Polycyclic Aromatic Hydrocarbon Emission Features: Applications to High Redshift Galaxies and Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Shipley, Heath; Papovich, Casey

    2015-08-01

    We provide a new robust star-formation rate (SFR) calibration using the luminosity from polycyclic aromatic hydrogen (PAH) molecules. The PAH features emit strongly in the mid-infrared (mid-IR; 3-19?m), mitigating dust extinction, and they are very luminous, containing 5-10% of the total IR luminosity in galaxies. We derive the calibration of the PAH luminosity as a SFR indicator using a sample of 105 star-forming galaxies covering a range of total IR luminosity, LIR = L(8-1000?m) = 109 - 1012 L? and redshift 0 < z < 0.6. The PAH luminosity correlates linearly with the SFR as measured by the dust-corrected H? luminosity (using the sum of the H? and rest-frame 24?m luminosity from Kennicutt et al. 2009), with tight scatter of ~0.15 dex, comparable to the scatter in the dust-corrected H? SFRs and Pa? SFRs. We show this relation is sensitive to galaxy metallicity, where the PAH luminosity of galaxies with Z < 0.7 Z? departs from the linear SFR relationship but in a behaved manor. We derive for this a correction to galaxies below solar metallicity. As a case study for observations with JWST, we apply the PAH SFR calibration to a sample of lensed galaxies at 1 < z < 3 with Spitzer Infrared Spectrograph (IRS) data, and we demonstrate the utility of PAHs to derive SFRs as accurate as those available from any other indicator. This new SFR indicator will be useful for probing the peak of the SFR density of the universe (1 < z < 3) and for studying the coevolution of star-formation and supermassive blackhole accretion contemporaneously in a galaxy.

  7. Mitotic catenation is monitored and resolved by a PKC?-regulated pathway.

    PubMed

    Brownlow, Nicola; Pike, Tanya; Zicha, Daniel; Collinson, Lucy; Parker, Peter J

    2014-01-01

    Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKC?. The PKC?-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKC? results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKC?-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2. PMID:25483024

  8. Chromosome and mitotic spindle dynamics in fission yeast kinesin-8 mutants

    NASA Astrophysics Data System (ADS)

    Crapo, Ammon M.; Gergley, Zachary R.; McIntosh, J. Richard; Betterton, M. D.

    2014-03-01

    Fission yeast proteins Klp5p and Klp6p are plus-end directed motors of the kinesin-8 family which promote microtubule (MT) depolymerization and also affect chromosome segregation, but the mechanism of these activities is not well understood. Using live-cell time-lapse fluorescence microscopy of fission yeast wild-type (WT) and klp5/6 mutant strains, we quantify and compare the dynamics of kinetochore motion and mitotic spindle length in 3D. In WT cells, the spindle, once formed, remains a consistent size and chromosomes are correctly organized and segregated. In kinesin-8 mutants, spindles undergo large length fluctuations of several microns. Kinetochore motions are also highly fluctuating, with kinetochores frequently moving away from the spindle rather than toward it. We observe transient pushing of chromosomes away from the spindle by as much as 10 microns in distance.

  9. Mitotic catenation is monitored and resolved by a PKCε-regulated pathway

    PubMed Central

    Brownlow, Nicola; Pike, Tanya; Zicha, Daniel; Collinson, Lucy; Parker, Peter J.

    2014-01-01

    Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKCε. The PKCε-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKCε results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKCε-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2. PMID:25483024

  10. Small feature sizes and high aperture ratio organic light-emitting diodes by using laser-patterned polyimide shadow masks

    NASA Astrophysics Data System (ADS)

    Kajiyama, Yoshitaka; Joseph, Kevin; Kajiyama, Koichi; Kudo, Shuji; Aziz, Hany

    2014-02-01

    A shadow mask technique capable of realizing high resolution (>330 pixel-per-inch) and 100% aperture ratio Organic Light-Emitting Diode (OLED) full color displays is demonstrated. The technique utilizes polyimide contact shadow masks, patterned by laser ablation. Red, green, and blue OLEDs with very small feature sizes (<25 ?m) are fabricated side by side on one substrate. OLEDs fabricated via this technique have the same performance as those made by established technology. This technique has a strong potential to achieve high resolution OLED displays via standard vacuum deposition processes even on flexible substrates.

  11. ETV6/RUNX1 abrogates mitotic checkpoint function and targets its key player MAD2L1

    PubMed Central

    Krapf, G; Kaindl, U; Kilbey, A; Fuka, G; Inthal, A; Joas, R; Mann, G; Neil, JC; Haas, OA; Panzer-Grmayer, ER

    2014-01-01

    Approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia have an ETV6/RUNX1 (E/R) gene fusion that results from a t(12;21). This genetic subgroup of leukemia is associated with near-triploidy, near-tetraploidy, and trisomy 21 as rather specific types of secondary changes. Here, we show that, unlike various controls, E/R-expressing Ba/F3 clones acquire a tetraploid karyotype on prolonged culture, corroborating the assumption that E/R may attenuate the mitotic checkpoint (MC). Consistent with this notion, E/R-expressing diploid murine and human cell lines have decreased proportions of cells with 4N DNA content and a lower mitotic index when treated with spindle toxins. Moreover, both RUNX1 and E/R regulate mitotic arrest-deficient 2 L1 (MAD2L1), an essential MC component, by binding to promoter-inherent RUNX1 sites, which results in down-regulation of MAD2L1 mRNA and protein in E/R-expressing cells. Forced expression of E/R also abolishes RUNX1-induced reporter activation, whereas E/R with a mutant DNA-binding site leads to only minor effects. Our data link for the first time E/R, MC, and MAD2L1 and provide new insights into the function of the E/R fusion gene product. Although tetraploidy is an almost exclusive feature of E/R-positive leukemias, its rarity within this particular subgroup implies that further yet unknown factors are required for its manifestation. PMID:20190817

  12. ETV6/RUNX1 abrogates mitotic checkpoint function and targets its key player MAD2L1.

    PubMed

    Krapf, G; Kaindl, U; Kilbey, A; Fuka, G; Inthal, A; Joas, R; Mann, G; Neil, J C; Haas, O A; Panzer-Grmayer, E R

    2010-06-01

    Approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia have an ETV6/RUNX1 (E/R) gene fusion that results from a t(12;21). This genetic subgroup of leukemia is associated with near-triploidy, near-tetraploidy, and trisomy 21 as rather specific types of secondary changes. Here, we show that, unlike various controls, E/R-expressing Ba/F3 clones acquire a tetraploid karyotype on prolonged culture, corroborating the assumption that E/R may attenuate the mitotic checkpoint (MC). Consistent with this notion, E/R-expressing diploid murine and human cell lines have decreased proportions of cells with 4N DNA content and a lower mitotic index when treated with spindle toxins. Moreover, both RUNX1 and E/R regulate mitotic arrest-deficient 2 L1 (MAD2L1), an essential MC component, by binding to promoter-inherent RUNX1 sites, which results in down-regulation of MAD2L1 mRNA and protein in E/R-expressing cells. Forced expression of E/R also abolishes RUNX1-induced reporter activation, whereas E/R with a mutant DNA-binding site leads to only minor effects. Our data link for the first time E/R, MC, and MAD2L1 and provide new insights into the function of the E/R fusion gene product. Although tetraploidy is an almost exclusive feature of E/R-positive leukemias, its rarity within this particular subgroup implies that further yet unknown factors are required for its manifestation. PMID:20190817

  13. Acrylamide effects on kinesin-related proteins of the mitotic/meiotic spindle

    SciTech Connect

    Sickles, Dale W. . E-mail: dsickles@mcg.edu; Sperry, Ann O. . E-mail: sperrya@ecu.edu; Testino, Angie; Friedman, Marvin

    2007-07-01

    The microtubule (MT) motor protein kinesin is a vital component of cells and organs expressing acrylamide (ACR) toxicity. As a mechanism of its potential carcinogenicity, we determined whether kinesins involved in cell division are inhibited by ACR similar to neuronal kinesin [Sickles, D.W., Brady, S.T., Testino, A.R., Friedman, M.A., and Wrenn, R.A. (1996). Direct effect of the neurotoxicant acrylamide on kinesin-based microtubule motility. Journal of Neuroscience Research 46, 7-17.] Kinesin-related genes were isolated from rat testes [Navolanic, P.M., and Sperry, A.O. (2000). Identification of isoforms of a mitotic motor in mammalian spermatogenesis. Biology of Reproduction 62, 1360-1369.], their kinesin-like proteins expressed in bacteria using recombinant DNA techniques and the effects of ACR, glycidamide (GLY) and propionamide (a non-neurotoxic metabolite) on the function of two of the identified kinesin motors were tested. KIFC5A MT bundling activity, required for mitotic spindle formation, was measured in an MT-binding assay. Both ACR and GLY caused a similar concentration-dependent reduction in the binding of MT; concentrations of 100 {mu}M ACR or GLY reduced its activity by 60%. KRP2 MT disassembling activity was assayed using the quantity of tubulin disassembled from taxol-stabilized MT. Both ACR and GLY inhibited KRP2-induced MT disassembly. GLY was substantially more potent; significant reductions of 60% were achieved by 500 {mu}M, a comparable inhibition by ACR required a 5 mM concentration. Propionamide had no significant effect on either kinesin, except KRP2 at 10 mM. This is the first report of ACR inhibition of a mitotic/meiotic motor protein. ACR (or GLY) inhibition of kinesin may be an alternative mechanism to DNA adduction in the production of cell division defects and potential carcinogenicity. We conclude that ACR may act on multiple kinesin family members and produce toxicities in organs highly dependent on microtubule-based functions.

  14. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in

  15. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

  16. Relationships among Repetitive Behaviors, Sensory Features, and Executive Functions in High Functioning Autism

    ERIC Educational Resources Information Center

    Boyd, Brian A.; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T.; Bodfish, James W.

    2009-01-01

    This study examined the relationship between repetitive behaviors and sensory processing issues in school-aged children with high functioning autism (HFA). Children with HFA (N = 61) were compared to healthy, typical controls (N = 64) to determine the relationship between these behavioral classes and to examine whether executive dysfunction

  17. Theories and Practices of Environmental Education in Quebec High Schools: Main Features of a Critical Diagnosis.

    ERIC Educational Resources Information Center

    Sauve, Lucie; Boutard, Armel; Begin, Rachel; Orellana, Isabel

    This paper reports on research about professional development programs in environmental education for high school teachers in Quebec (Canada). A diagnostic research study was conducted to attempt to answer two questions: (1) what is the current status of environmental education in this sector of formal education?; and (2) how is environmental

  18. Large Erosional Features on the Cascadia Accretionary Wedge Imaged with New High-Resolution Multibeam Bathymetry and Seismic Datasets

    NASA Astrophysics Data System (ADS)

    Beeson, J. W.; Goldfinger, C.

    2013-12-01

    Utilizing new high resolution multibeam bathymetric data along with chirp sub-bottom and multichannel seismic reflection (MCS) data, we identified remarkable erosional features on the toe of the Cascadia accretionary wedge near Willapa Canyon, offshore Washington, USA. Bathymetric data was compiled from the Cascadia Open-Access Seismic Transects (COAST) cruise and from the site survey cruise for the Cascadia Initiative. These features loosely resemble slope failures of the frontal thrust, but can be distinguished from such failures by several key features: They incise the crest of the frontal thrust and encompass the landward limb; They have floors below the level of the abyssal plain, similar to plunge pool morphology; They show no evidence of landslide blocks at the base of the slope indicative of block sliding. The features where likely formed during the latest Pleistocene based on post event deposition, cross-cutting relationships with Juan de Fuca Channel and the Willapa Channel levees and wave field, and post event slip on the frontal thrust of the Cascadia accretionary prism. The Holocene levees of both Willapa Channel and Juan de Fuca Channel overlap these older features, and clearly place an upper bound on the age of the erosional features in the latest Pleistocene. A lower bound is estimated from a sub-bottom profile that images ~30 meters of post scour sediment fill. Using existing literature of Holocene and Pleistocene sedimentation rates we estimate a lower age bound between ~23,000 - 56,000 y.b.p. We also map a fault scarp within the erosional feature, with ~60 m of vertical offset. Using multi-channel seismic reflection profiles from the COAST cruise we interpret this scarp as the surface expression of the landward vergent frontal thrust fault. The apparent short duration of the erosional event along the seaward margin of the accretionary wedge, coupled with the presence of the fresh fault scarp within the erosion zone, are indicative of a dormant feature with significant time required to develop the scarp after cessation of the causative process. Based on morphology, dissimilarity with other submarine features, and available age constraints, we infer that these features were most likely formed during the glacial lake outpouring in the Pacific Northwest known as the Missoula floods which occurred 13,000-19,500 y.b.p. The features themselves bear a strong resemblance to 'coulees' formed during the same glacial events onshore, and the outpourings through Willapa Channel are consistent with previous inferences of the deposition of Missoula Flood deposits in Escanaba Trough. If this timing is correct, the slip rate along the Cascadia frontal thrust can be estimated using fault geometry and scarp height as 2.8 - 4.1 mm/yr.

  19. Phosphorylation of Xenopus p31(comet) potentiates mitotic checkpoint exit.

    PubMed

    Mo, Min; Arnaoutov, Alexei; Dasso, Mary

    2015-12-17

    p31(comet) plays an important role in spindle assembly checkpoint (SAC) silencing. However, how p31(comet)'s activity is regulated remains unclear. Here we show that the timing of M-phase exit in Xenopus egg extracts (XEEs) depends upon SAC activity, even under conditions that are permissive for spindle assembly. p31(comet) antagonizes the SAC, promoting XEE progression into anaphase after spindles are fully formed. We further show that mitotic p31(comet) phosphorylation by Inhibitor of nuclear factor ?-B kinase-? (IKK-?) enhances this role in SAC silencing. Together, our findings implicate IKK-? in the control of anaphase timing in XEE through p31(comet) activation and SAC downregulation. PMID:25892037

  20. Resurrecting remnants: The lives of post-mitotic midbodies

    PubMed Central

    Chen, Chun-Ting; Ettinger, Andreas W.; Huttner, Wieland B.; Doxsey, Stephen J.

    2014-01-01

    Around a century ago, the midbody was described as a structural assembly within the intercellular bridge during cytokinesis, which served to connect the two future daughter cells. The midbody has become the focus of intense investigation through the identification of a growing number of diverse cellular and molecular pathways that localize to the midbody and contribute to its cytokinetic functions ranging from selective vesicle trafficking, regulated microtubule, actin and ESCRT filament assembly and disassembly, and post-translational modification, such as ubiquitination. More recent studies revealed new and unexpected functions of midbodies that occur in post-mitotic cells. In this article, we provide a historical perspective, discuss exciting new roles for midbodies beyond their cytokinetic function and speculate on their potential contributions to pluripotency. PMID:23245592

  1. Mitotic Exit and Separation of Mother and Daughter Cells

    PubMed Central

    Weiss, Eric L.

    2012-01-01

    Productive cell proliferation involves efficient and accurate splitting of the dividing cell into two separate entities. This orderly process reflects coordination of diverse cytological events by regulatory systems that drive the cell from mitosis into G1. In the budding yeast Saccharomyces cerevisiae, separation of mother and daughter cells involves coordinated actomyosin ring contraction and septum synthesis, followed by septum destruction. These events occur in precise and rapid sequence once chromosomes are segregated and are linked with spindle organization and mitotic progress by intricate cell cycle control machinery. Additionally, critical parts of the mother/daughter separation process are asymmetric, reflecting a form of fate specification that occurs in every cell division. This chapter describes central events of budding yeast cell separation, as well as the control pathways that integrate them and link them with the cell cycle. PMID:23212898

  2. Mitotic wavefronts mediated by mechanical signaling in early Drosophila embryos

    NASA Astrophysics Data System (ADS)

    Kang, Louis; Idema, Timon; Liu, Andrea; Lubensky, Tom

    2013-03-01

    Mitosis in the early Drosophila embryo demonstrates spatial and temporal correlations in the form of wavefronts that travel across the embryo in each cell cycle. This coordinated phenomenon requires a signaling mechanism, which we suggest is mechanical in origin. We have constructed a theoretical model that supports nonlinear wavefront propagation in a mechanically-excitable medium. Previously, we have shown that this model captures quantitatively the wavefront speed as it varies with cell cycle number, for reasonable values of the elastic moduli and damping coefficient of the medium. Now we show that our model also captures the displacements of cell nuclei in the embryo in response to the traveling wavefront. This new result further supports that mechanical signaling may play an important role in mediating mitotic wavefronts.

  3. Special features of high-speed projectile interaction with barriers protected by a water layer

    NASA Astrophysics Data System (ADS)

    Afanas'eva, S. A.; Belov, N. N.; Burkin, V. V.; D'yachkovskii, A. S.; Evtyushkin, E. V.; Zykov, E. N.; Ishchenko, A. N.; Monakhov, R. Yu.; Rodionov, A. A.; Khabibullin, M. V.; Yugov, N. T.

    2013-09-01

    The stress-strain state (SSS) of projectiles is investigated when a high-speed projectile enters water and interacts with barriers protected by a water layer. Experimental investigations are carried out using a high-speed ballistic setup. Calculations are performed within the framework of mechanics of continuous media for an elastic plastic model of a solid with allowance for fracture and hydrodynamic water model. Depending on the projectile speed, different SSS regimes are observed: from small deformed at a speed of ?1 km/s to fractured at a speed of ?2 km/s. Calculation technique allows distances in water to be determined at which the metal barrier can be punched for the inertial model.

  4. Peculiar Magnetotransport Features of Ultranarrow Graphene Nanoribbons under High Magnetic Field.

    PubMed

    Shen, Haoliang; Cresti, Alessandro; Escoffier, Walter; Shi, Yi; Wang, Xinran; Raquet, Bertrand

    2016-02-23

    Through magnetotransport measurements, we investigate ultrasmooth graphene bilayer nanoribbons obtained by multiwall carbon nanotube unzipping, under a high magnetic field up to 55 T. The high quality of the samples allows us to observe a Hall quantization in ribbons as narrow as 20 nm. The presence, for certain samples, of isolated peaks in the resistance plateau is found to be related to a very moderate long-range disorder, which induces magnetic-field-dependent interedge scattering. Tight-binding numerical simulations of electron transport illustrate and confirm this picture. Our study provides important insights into the quantum Hall effect in quasi-1D systems and indicates possible lines for future investigations of the nonchiral edge states induced by zigzag nanoribbon sections. PMID:26649888

  5. Delocalization of the microtubule motor Dynein from mitotic spindles by the human papillomavirus E7 oncoprotein is not sufficient for induction of multipolar mitoses.

    PubMed

    Nguyen, Christine L; McLaughlin-Drubin, Margaret E; Mnger, Karl

    2008-11-01

    Dynein is a minus end-directed microtubule motor that transports numerous cargoes throughout the cell. During mitosis, dynein motor activity is necessary for the positioning of spindle microtubules and has also been implicated in inactivating the spindle assembly checkpoint. Mutations in dynein motor and/or accessory proteins are associated with human disease, including cancer, and the delocalization of dynein from mitotic spindles has been correlated with an increased incidence of multipolar spindle formation in some cancer cells that contain supernumerary centrosomes. The high-risk human papillomavirus type 16 (HPV16) E7 oncoprotein induces centrosome overduplication and has been shown to cause multipolar mitotic spindle formation, a diagnostic hallmark of HPV-associated neoplasias. Here, we show that HPV16 E7 expression leads to an increased population of mitotic cells with dynein delocalized from the mitotic spindle. This function maps to sequences of HPV16 E7 that are distinct from the region necessary for centrosome overduplication. However, contrary to previous reports, we provide evidence that dynein delocalization by HPV16 E7 is neither necessary nor sufficient to cause the formation of multipolar mitoses. PMID:18974113

  6. Features of creation of highly accurate models of triumphal pylons for archaeological reconstruction

    NASA Astrophysics Data System (ADS)

    Grishkanich, A. S.; Sidorov, I. S.; Redka, D. N.

    2015-12-01

    Cited a measuring operation for determining the geometric characteristics of objects in space and geodetic survey objects on the ground. In the course of the work, data were obtained on a relative positioning of the pylons in space. There are deviations from verticality. In comparison with traditional surveying this testing method is preferable because it allows you to get in semi-automated mode, the CAD model of the object is high for subsequent analysis that is more economical-ly advantageous.

  7. Interface recombination feature in metal-semiconductor junction at high photo-excitation

    NASA Astrophysics Data System (ADS)

    Konin, A.

    2014-09-01

    A theory of the photo-induced electromotive force in a p-type semiconductor accounting for the energy band bending and interface recombination dependence on excitation level is developed. It is shown that at high photo-excitation the effective interface recombination velocity in the metal-semiconductor junction is negligible compared with the volume one, when the surface potential is less than its critical value. The photo-induced electromotive force value is maximal at this condition.

  8. Epidemiological features of pertussis resurgence based on community populations with high vaccination coverage in China.

    PubMed

    Huang, H; Zhu, T; Gao, C; Gao, Z; Liu, Y; Ding, Y; Sun, J; Guo, L; Liu, P; Chen, D; Wang, L; Wu, S; Zhang, Y

    2015-07-01

    Active symptom surveillance was applied to three selected communities ( 160,147 persons) in Tianjin from 2010 to 2012. We examined 1089 individuals showing pertussis-like symptoms, of which 1022 nasopharyngeal specimens were tested for pertussis by polymerase chain reaction and 802 sera for anti-pertussis toxin antibodies. Of the total cases tested, 113 were confirmed, and their demographic, clinical, and vaccination-related data were collected. The annual incidence was 23.52 cases/100,000 persons among communities, which was 16.22 times that obtained via hospital reports for the same period (P < 0.001). The actual incidence in the 15-69 years age group was most significantly underestimated by hospitals, given that it was 43.08 times that of the reported hospital rate. Among the cases aged <15 years, 84.5% were individuals who had been fully vaccinated. The misdiagnosis rate was as high as 94.69%, and only 5.31% of the confirmed pertussis cases were properly diagnosed as pertussis at their first medical visit. Pertussis incidence in China has been severely underestimated and this was in part due to a high misdiagnosis rate. Adolescents and adults have become new high-risk populations. Future work should focus on reinforcing immunization programmes, especially among adolescents and adults. PMID:25286969

  9. Features of >130 Gamma-Ray Bursts at high energy: towards the 2nd Fermi LAT GRB catalog

    NASA Astrophysics Data System (ADS)

    Vianello, Giacomo; Omodei, Nicola; Fermi LAT Collaboration

    2016-01-01

    The high-energy emission from Gamma-Ray Bursts is a formidable probe for extreme physics, calling for highly relativistic sources with very large Lorentz factors. Despite the advancements prompted by observations from the Fermi Large Area Telescope and the Fermi Gamma-Ray Burst Monitor, as well as other observatories, many questions remain open, especially on radiative processes and mechanisms. We present here the most extensive search for GRBs at high energies performed so far, featuring a detection efficiency more than 50% better than previous works, and returning more than 130 detections. With this sample size, much larger than the 35 detections presented in the first Fermi/LAT GRB catalog, we are able to assess the characteristics of the population of GRBs at high energy with unprecedented sensitivity. We will review the preliminary results of this work, as well as their interpretation.

  10. Very compact, high-stability electrostatic actuator featuring contact-free self-limiting displacement

    DOEpatents

    Rodgers, M. Steven (Albuquerque, NM); Miller, Samuel L. (Albuquerque, NM)

    2003-01-01

    A compact electrostatic actuator is disclosed for microelectromechanical (MEM) applications. The actuator utilizes stationary and moveable electrodes, with the stationary electrodes being formed on a substrate and the moveable electrodes being supported above the substrate on a frame. The frame provides a rigid structure which allows the electrostatic actuator to be operated at high voltages (up to 190 Volts) to provide a relatively large actuation force compared to conventional electrostatic comb actuators which are much larger in size. For operation at its maximum displacement, the electrostatic actuator is relatively insensitive to the exact value of the applied voltage and provides a self-limiting displacement.

  11. Brachytelephalangy with sparing of the fifth distal phalanx: a feature highly suggestive of Keutel syndrome.

    PubMed

    Miller, Stephen F

    2003-03-01

    Keutel syndrome (KS) is a rare, autosomal recessive condition characterized by diffuse cartilaginous calcification, nasal hypoplasia, brachytelephalangy, and peripheral pulmonary stenosis. A review of the literature produced only 15 reported patients, of whom plain radiographs of the hand or a detailed report are available for review in ten. A distinctive pattern of broadening and shortening of the first through fourth distal phalanges, with sparing of the fifth distal phalanx, is seen in seven of these patients. Two additional patients with Keutel syndrome and this identical finding are presented. I suggest that this pattern of brachytelephalangy is sensitive and highly suggestive of the diagnosis of Keutel syndrome. PMID:12612818

  12. The Features of Carbon Nanotubes Grown in High Isostatic Pressure Apparatus from the Nanodiamond Powder

    NASA Astrophysics Data System (ADS)

    Buranova, Yu. S.; Kulnitskiy, B. A.; Perezhogin, I. A.; Bagramov, R. H.; Dubitsky, G. A.; Blank, V. D.

    2013-05-01

    Multiwalled carbon nanotubes were synthesized in high isostatic pressure (HIP) apparatus in nitrogen at 1650 C and 2 MPa. The synthesis was performed with nanodiamonds as a precursor of carbon and with ferrocene as a catalyst. Transmission electron microscopy studies demonstrate that the product of the synthesis contains carbon nanotubes filled with iron-based nanoparticles. It was established that in the most of the cases these nanoparticles represent themselves iron carbide Fe3C (cementite). Several times we observed pure iron (?- and ?-Fe) inside the nanotubes. The orientation of the iron and iron carbide particles with respect to the nanotubes axes was investigated.

  13. Uncertainty-based feature learning for skin lesion matching using a high order MRF optimization framework.

    PubMed

    Mirzaalian, Hengameh; Lee, Tim K; Hamarneh, Ghassan

    2012-01-01

    We formulate the pigmented-skin-lesion (PSL) matching problem as a relaxed labeling of an association graph. In this graph labeling problem, each node represents a mapping between a PSL from one image to a PSL in the second image and the optimal labels are those optimizing a high order Markov Random Field energy (MRF). The energy is made up of unary, binary, and ternary energy terms capturing the likelihood of matching between the points, edges, and cliques of two graphs representing the spatial distribution of the two PSL sets. Following an exploration of various MRF energy terms, we propose a novel entropy energy term encouraging solutions with low uncertainty. By interpreting the relaxed labeling as a measure of confidence, we further leverage the high confidence matching to sequentially constrain the learnt objective function defined on the association graph. We evaluate our method on a large set of synthetic data as well as 56 pairs of real dermatological images. Our proposed method compares favorably with the state-of-the-art. PMID:23286037

  14. Unique features of high-density lipoproteins in the Japanese: in population and in genetic factors.

    PubMed

    Yokoyama, Shinji

    2015-04-01

    Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL) levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Accordingly, lower HDL seems to contribute more to the development of coronary heart disease (CHD) than an increase in non-HDL lipoproteins at a population level in Japan. Interestingly, average HDL levels in Japan have increased further in the past two decades, and are markedly higher than in Western populations. The reasons and consequences for public health of this increase are still unknown. Simulation for the efficacy of raising HDL cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent by reducing low-density lipoprotein cholesterol predicted by simulation or achieved in a statin trial. On the other hand, a substantial portion of hyperalphalipoproteinemic population in Japan is accounted for by genetic deficiency of cholesteryl ester transfer protein (CETP), which is also commonly unique in East Asian populations. It is still controversial whether CETP mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential screening factor for historic accumulation of CETP deficiency in East Asia. PMID:25849946

  15. Understanding the structural features of high-amylose maize starch through hydrothermal treatment.

    PubMed

    Yang, Jianing; Xie, Fengwei; Wen, Wenqiang; Chen, Ling; Shang, Xiaoqin; Liu, Peng

    2016-03-01

    In this study, high-amylose starches were hydrothermally-treated and the structural changes were monitored with time (up to 12h) using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), small-angle X-ray scattering (SAXS), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). When high-amylose starches were treated in boiling water, half-shell-like granules were observed by SEM, which could be due to the first hydrolysis of the granule inner region (CLSM). This initial hydrolysis could also immediately (0.5h) disrupt the semi-crystalline lamellar regularity (SAXS) and dramatically reduce the crystallinity (XRD); but with prolonged time of hydrothermal treatment (≥2h), might allow the perfection or formation of amylose single helices, resulting in slightly increased crystallinity (XRD and DSC). These results show that the inner region of granules is composed of mainly loosely-packed amylopectin growth rings with semi-crystalline lamellae, which are vulnerable under gelatinization or hydrolysis. In contrast, the periphery is demonstrated to be more compact, possibly composed of amylose and amylopectin helices intertwined with amylose molecules, which require greater energy input (higher temperature) for disintegration. PMID:26708428

  16. Unique Features of High-Density Lipoproteins in the Japanese: In Population and in Genetic Factors

    PubMed Central

    Yokoyama, Shinji

    2015-01-01

    Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL) levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Accordingly, lower HDL seems to contribute more to the development of coronary heart disease (CHD) than an increase in non-HDL lipoproteins at a population level in Japan. Interestingly, average HDL levels in Japan have increased further in the past two decades, and are markedly higher than in Western populations. The reasons and consequences for public health of this increase are still unknown. Simulation for the efficacy of raising HDL cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent by reducing low-density lipoprotein cholesterol predicted by simulation or achieved in a statin trial. On the other hand, a substantial portion of hyperalphalipoproteinemic population in Japan is accounted for by genetic deficiency of cholesteryl ester transfer protein (CETP), which is also commonly unique in East Asian populations. It is still controversial whether CETP mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential screening factor for historic accumulation of CETP deficiency in East Asia. PMID:25849946

  17. Intramedullary gangliogliomas: histopathologic and molecular features of 25 cases.

    PubMed

    Gessi, Marco; Drner, Evelyn; Dreschmann, Verena; Antonelli, Manila; Waha, Andreas; Giangaspero, Felice; Gnekow, Astrid; Pietsch, Torsten

    2016-03-01

    Gangliogliomas are uncommon glioneuronal tumors, which usually arise in the cerebral hemispheres and occasionally in the brain stem. Gangliogliomas occurring in the spinal cord are extremely rare. In this study, we analyzed the clinical, histopathologic, and molecular features of 25 spinal gangliogliomas. The cases included in our series affected mostly children and young adults (15 males and 10 females; mean age, 20 years; median age, 14 years; age range, 1-72 years) and were predominantly localized in the cervical and thoracic spine. From the clinical point of view (detailed follow-up available for 9 pediatric cases; mean follow-up: 2 years 10 months; range, 3 months to 5 years 10 months), most patients showed stable disease after subtotal resection. Radiotherapy was rarely used as adjuvant treatment. Histologically, gangliogliomas (WHO grade I) (21 cases) showed features largely similar to their supratentorial counterparts. Anaplastic gangliogliomas (World Health Organization grade III) (4 cases) showed features of anaplasia (including high cellularity and increased mitotic and proliferation activity). From a molecular point of view, only 2 tumors (2/19, 11%) harbored a BRAF(V600E) mutation. In conclusion, although spinal gangliogliomas display histologic and clinical features similar to their supratentorial counterparts, they show a relatively low frequency of BRAF(V600E) mutations, alteration otherwise common in hemispheric and brain stem gangliogliomas. PMID:26826417

  18. Extraction of Features from High-resolution 3D LiDaR Point-cloud Data

    NASA Astrophysics Data System (ADS)

    Keller, P.; Kreylos, O.; Hamann, B.; Kellogg, L. H.; Cowgill, E. S.; Yikilmaz, M. B.; Hering-Bertram, M.; Hagen, H.

    2008-12-01

    Airborne and tripod-based LiDaR scans are capable of producing new insight into geologic features by providing high-quality 3D measurements of the landscape. High-resolution LiDaR is a promising method for studying slip on faults, erosion, and other landscape-altering processes. LiDaR scans can produce up to several billion individual point returns associated with the reflection of a laser from natural and engineered surfaces; these point clouds are typically used to derive a high-resolution digital elevation model (DEM). Currently, there exist only few methods that can support the analysis of the data at full resolution and in the natural 3D perspective in which it was collected by working directly with the points. We are developing new algorithms for extracting features from LiDaR scans, and present method for determining the local curvature of a LiDaR data set, working directly with the individual point returns of a scan. Computing the curvature enables us to rapidly and automatically identify key features such as ridge-lines, stream beds, and edges of terraces. We fit polynomial surface patches via a moving least squares (MLS) approach to local point neighborhoods, determining curvature values for each point. The size of the local point neighborhood is defined by a user. Since both terrestrial and airborne LiDaR scans suffer from high noise, we apply additional pre- and post-processing smoothing steps to eliminate unwanted features. LiDaR data also captures objects like buildings and trees complicating greatly the task of extracting reliable curvature values. Hence, we use a stochastic approach to determine whether a point can be reliably used to estimate curvature or not. Additionally, we have developed a graph-based approach to establish connectivities among points that correspond to regions of high curvature. The result is an explicit description of ridge-lines, for example. We have applied our method to the raw point cloud data collected as part of the GeoEarthScope B-4 project on a section of the San Andreas Fault (Segment SA09). This section provides an excellent test site for our method as it exposes the fault clearly, contains few extraneous structures, and exhibits multiple dry stream-beds that have been off-set by motion on the fault.

  19. Microstructure features of high-entropy equiatomic cast AlCrFeCoNiCu alloys

    NASA Astrophysics Data System (ADS)

    Ivchenko, M. V.; Pushin, V. G.; Uksusnikov, A. N.; Wanderka, N.

    2013-06-01

    The structural and phase transformations that take place in the cast high-entropy equiatomic alloy AlCrFeCoNiCu after solidification, homogenizing heat treatment, and cooling have been studied. Analytical transmission microscopy, scanning electron microscopy, X-ray energy dispersive spectroscopy, and X-ray diffraction analysis were used to conduct the studies. The elastic modulus, nano-, and microhardness have been measured. The alloy decomposition has been found to occur with the precipitation of no less than six nanoscale phases with different morphologies, structures ( A2, B2, L12), and chemical compositions. All the nanophases are multicomponent solid solutions enriched with several elements, which indicates the pronounced elemental and phase nanomodulation over the alloy volume.

  20. Features of brittle damages and hydrogen impregnation of high-pressure boiler tube metal

    SciTech Connect

    Vainman, A.B.; Smiyan, O.D.; Girnyi, S.I.; Kostyuchenko, N.P.; Vasilik, A.V.; Melekhov, R.K.

    1988-01-01

    A significant number of failures encountered in high-pressure steam boilers of thermal electric power stations are caused by damage of the tubes of the steam superheaters, which are made of 20, 12Kh1MF, 12Kh2MFSR and 12Kh18N10T steels. A statistical analysis made by the authors determined that a large number of the failures result from the action of hydrogen on the tubes. In this paper, the mechanisms of hydrogen diffusion, corrosion crack propagation, and brittle failure for steam superheater tubes were analyzed. Hydrogen-related intergranular cracking and thermal fatigue were assessed for the tube steels. It was concluded that hydrogen had a significant effect on processes of crack origin and propagation both in the superheater and in the unheated tubes of the boilers.

  1. Transmission electron microscopy specimen preparation perpendicular to the long axis of high aspect ratio features

    SciTech Connect

    Irwin, R. B.; Anciso, A.; Jones, P. J.; Glenn, A. L.; Williams, B. L.; Sridhar, S.; Arshad, S.

    2009-11-15

    A new variation of transmission electron microscopy (TEM) specimen preparation is introduced. By thinning a tall high aspect ratio structure perpendicular to the long dimension (i.e., from the side) rather than from perpendicular to the short dimension (either the top or the bottom), it is possible to obtain a more uniformly thin TEM specimen over the entire long dimension of the structure. This article will describe the rational for this variation in specimen preparation. The necessary modifications of four different specimen preparation methods (in situ lift-out, traditional H-bar, ex situ lift-out, and tripod polishing) will be discussed and images of specimens obtained by both of these first two methods will be shown. Additional potential advantages and other applications of this specimen preparation method will be covered.

  2. DE/ISIS conjunction comparisons of high-latitude electron density features

    NASA Technical Reports Server (NTRS)

    Hoegy, Walter R.; Benson, Robert F.

    1988-01-01

    This paper presents a comparison between the ISIS-1 and -2 topside sounder measurements of electron number density, N(e), with the in situ ion and N(e) measurements by the Langmuir probe aboard the Dynamics Explorer 2 (DE 2) during four high-latitude ISIS/DE magnetic field-aligned conjunctions. The ISIS-derived N(e) values, even at the greatest distance from the sounder, were found to agree with the Langmuir probe measurements to within about 30 percent over a density range of more than two decades on three of the four comparisons; the fourth comparison which included data with strong N(e) irregularities, showed a difference of 60 percent.

  3. The Structure, Water Budget, and Radiational Features of a High-Latitude Warm Front.

    NASA Astrophysics Data System (ADS)

    Hanesiak, John M.; Stewart, Ronald E.; Szeto, Kit K.; Hudak, David R.; Leighton, Henry G.

    1997-06-01

    On 30 September 1994 an Arctic low pressure system passed over the southern Beaufort Sea area of northern Canada and research aircraft observations were made within and around the warm front of the storm. This study is unique in that the warm front contained subzero centigrade temperatures across the entire frontal region. The overall structure of the warm front and surrounding region was similar to midlatitude storms; however, the precipitation rates, liquid water content magnitudes, horizontal and vertical winds, vertical wind shear, turbulence, and thermal advection were very weak. In addition, a low-level jet and cloud bands were aligned parallel to the warm front, near-neutral stability occurred within and around the front, and conditional symmetric instability was likely occurring. A steep frontal region resulted from strong Coriolis influences that in turn limited the amount of cloud and precipitation ahead of the system. The precipitation efficiency of the storm was high (60%) but is believed to be highly dependent on the stage of development. The mesoscale frontogenetic forcing was primarily controlled by the tilting of isentropic surfaces with confluence/convergence being the secondary influence. Sublimation contributions may have been large in the earlier stages of storm development. Satellite and aircraft radiometers underestimated cloud top heights by as much as 4 km and this was mostly due to the near transparency of the lofted ice layer in the upper portion of the storm. Maximum surface solar radiation deficits ranged between 91 W m2 and 187 W m2 at two surface observing sites. This common type of cloud system must have a major impact on the water and energy cycles of northern Canada in the autumn and therefore must be well accounted for within climate models.

  4. Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.

    PubMed

    Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

    2014-10-01

    The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome. PMID:26038499

  5. Resonant nanocluster technologyfrom optical coding and high quality security features to biochips

    NASA Astrophysics Data System (ADS)

    Bauer, G.; Hassmann, J.; Walter, H.; Haglmller, J.; Mayer, C.; Schalkhammer, T.

    2003-12-01

    Metal clusters deposited on a substrate and positioned at a nanometric distance from a wave-reflecting layer act as nanoresonators able to receive, store and transmit energy within the visible and infrared range of the spectrum. Among the unique effects of these metal nanocluster assemblies are high local field enhancement and nanoscale resonant behaviour driving optical absorption in the visible and infrared range of the spectrum. In these types of devices and sensors the precise nanometric assembly coupling the local field surrounding a cluster is critical for allowing resonance with other elements interacting with this field. In particular, the cluster-mirror distance or the cluster-fluorophore distance gives rise to a variety of enhancement phenomena (e.g. resonant-enhanced fluorescence, REF). Depending on the desired application this 'resonance' distance is tuned from 5 up to 500 nm. High-throughput transducers using metal cluster resonance technology are based on surface enhancement of light absorption by metal clusters (surface-enhanced absorption, SEA). These devices can be used for detection of biorecognition binding as well as structural changes in nucleic acids, proteins or any polymer. The optical property made use of in the analytical application of metal cluster films is so-called anomalous absorption. An absorbing film of clusters is positioned 10-400 nm from an electromagnetic wave-reflecting layer. At a well-defined mirror-cluster distance the reflected electromagnetic field has the same phase at the position of the absorbing cluster as the incident field. This feedback mechanism strongly enhances the effective cluster absorption coefficient. These systems are characterized by a narrow reflection minimum whose spectral position shifts sensitively with interlayer thickness, because a given cluster-mirror distance and wavelength defines the optimum phase.

  6. Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus

    PubMed Central

    Kim, Young-Il; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Yoon, Sun-Woo; Park, Su-Jin; Kim, Se Mi; Choi, Eun-Ji; Si, Young-Jae; Lee, Ok-Jun; Shim, Woo-Sub; Kim, Si-Wook; Mo, In-Pil; Bae, Yeonji; Lim, Yong Taik; Sung, Moon Hee; Kim, Chul-Joong; Webby, Richard J; Webster, Robert G; Choi, Young Ki

    2014-01-01

    The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome. PMID:26038499

  7. Structural features and mechanical properties of austenitic Hadfield steel after high-pressure torsion and subsequent high-temperature annealing

    NASA Astrophysics Data System (ADS)

    Tukeeva, M. S.; Melnikov, E. V.; Maier, H. J.; Astafurova, E. G.

    2012-06-01

    Mechanisms of structure fragmentation and strengthening of single crystals of a Hadfield steel after warm torsion under high-pressure torsion (HPT) and subsequent annealing in a temperature range of 400-800C have been studied. Multiple twinning and formation of ultrafine carbides upon HPT at 400C ( P = 5 GPa) promote rapid fragmentation of the microstructure. They are responsible for the high mechanical properties of the steel after HPT and the thermal stability of the microstructure up to an annealing temperature of 500C.

  8. The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint

    PubMed Central

    1996-01-01

    M-phase checkpoints inhibit cell division when mitotic spindle function is perturbed. Here we show that the Saccharomyces cerevisiae MPS1 gene product, an essential protein kinase required for spindle pole body (SPB) duplication (Winey et al., 1991; Lauze et al., 1995), is also required for M-phase check-point function. In cdc31-2 and mps2-1 mutants, conditional failure of SPB duplication results in cell cycle arrest with high p34CDC28 kinase activity that depends on the presence of the wild-type MAD1 checkpoint gene, consistent with checkpoint arrest of mitosis. In contrast, mps1 mutant cells fail to duplicate their SPBs and do not arrest division at 37 degrees C, exhibiting a normal cycle of p34CDC28 kinase activity despite the presence of a monopolar spindle. Double mutant cdc31-2, mps1-1 cells also fail to arrest mitosis at 37 degrees C, despite having SPB structures similar to cdc31-2 single mutants as determined by EM analysis. Arrest of mitosis upon microtubule depolymerization by nocodazole is also conditionally absent in mps1 strains. This is observed in mps1 cells synchronized in S phase with hydroxyurea before exposure to nocodazole, indicating that failure of checkpoint function in mps1 cells is independent of SPB duplication failure. In contrast, hydroxyurea arrest and a number of other cdc mutant arrest phenotypes are unaffected by mps1 alleles. We propose that the essential MPS1 protein kinase functions both in SPB duplication and in a mitotic checkpoint monitoring spindle integrity. PMID:8567717

  9. Partial inhibition of Cdk1 in G 2 phase overrides the SAC and decouples mitotic events.

    PubMed

    McCloy, Rachael A; Rogers, Samuel; Caldon, C Elizabeth; Lorca, Thierry; Castro, Anna; Burgess, Andrew

    2014-01-01

    Entry and progression through mitosis has traditionally been linked directly to the activity of cyclin-dependent kinase 1 (Cdk1). In this study we utilized low doses of the Cdk1-specific inhibitor, RO3306 from early G 2 phase onwards. Addition of low doses of RO3306 in G 2 phase induced minor chromosome congression and segregation defects. In contrast, mild doses of RO3306 during G 2 phase resulted in cells entering an aberrant mitosis, with cells fragmenting centrosomes and failing to fully disassemble the nuclear envelope. Cells often underwent cytokinesis and metaphase simultaneously, despite the presence of an active spindle assembly checkpoint, which prevented degradation of cyclin B1 and securin, resulting in the random partitioning of whole chromosomes. This highly aberrant mitosis produced a significant increase in the proportion of viable polyploid cells present up to 3 days post-treatment. Furthermore, cells treated with medium doses of RO3306 were only able to reach the threshold of Cdk1 substrate phosphorylation required to initiate nuclear envelope breakdown, but failed to reach the levels of phosphorylation required to correctly complete pro-metaphase. Treatment with low doses of Okadaic acid, which primarily inhibits PP2A, rescued the mitotic defects and increased the number of cells that completed a normal mitosis. This supports the current model that PP2A is the primary phosphatase that counterbalances the activity of Cdk1 during mitosis. Taken together these results show that continuous and subtle disruption of Cdk1 activity from G 2 phase onwards has deleterious consequences on mitotic progression by disrupting the balance between Cdk1 and PP2A. PMID:24626186

  10. Partial inhibition of Cdk1 in G2 phase overrides the SAC and decouples mitotic events

    PubMed Central

    McCloy, Rachael A; Rogers, Samuel; Caldon, C Elizabeth; Lorca, Thierry; Castro, Anna; Burgess, Andrew

    2014-01-01

    Entry and progression through mitosis has traditionally been linked directly to the activity of cyclin-dependent kinase 1 (Cdk1). In this study we utilized low doses of the Cdk1-specific inhibitor, RO3306 from early G2 phase onwards. Addition of low doses of RO3306 in G2 phase induced minor chromosome congression and segregation defects. In contrast, mild doses of RO3306 during G2 phase resulted in cells entering an aberrant mitosis, with cells fragmenting centrosomes and failing to fully disassemble the nuclear envelope. Cells often underwent cytokinesis and metaphase simultaneously, despite the presence of an active spindle assembly checkpoint, which prevented degradation of cyclin B1 and securin, resulting in the random partitioning of whole chromosomes. This highly aberrant mitosis produced a significant increase in the proportion of viable polyploid cells present up to 3 days post-treatment. Furthermore, cells treated with medium doses of RO3306 were only able to reach the threshold of Cdk1 substrate phosphorylation required to initiate nuclear envelope breakdown, but failed to reach the levels of phosphorylation required to correctly complete pro-metaphase. Treatment with low doses of Okadaic acid, which primarily inhibits PP2A, rescued the mitotic defects and increased the number of cells that completed a normal mitosis. This supports the current model that PP2A is the primary phosphatase that counterbalances the activity of Cdk1 during mitosis. Taken together these results show that continuous and subtle disruption of Cdk1 activity from G2 phase onwards has deleterious consequences on mitotic progression by disrupting the balance between Cdk1 and PP2A. PMID:24626186

  11. Collecting Inexpensive High Resolution Aerial and Stereo Images of Small- to Mid-Scale Geomorphic and Tectonic Features

    NASA Astrophysics Data System (ADS)

    Wheelwright, R. J.; White, W. S.; Willis, J. B.

    2010-12-01

    Methods for collecting accurate, mm- to cm-scale stereoscopic aerial imagery of both small- and mid-scale geomorphic features are developed for a one-time cost of under $1500. High resolution aerial images are valuable for documenting and analyzing small- to mid-scale geomorphic and tectonic features. However, collecting images of mid-scale features such as landslides, rock glaciers, fault scarps, and cinder cones is expensive and makes studies that rely on high resolution repeat imagery prohibitive for undergraduate geology departments with limited budgets. In addition to cost, collecting images of smaller scale geomorphic features such as gravel bars is often impeded by overhanging vegetation or other features in the immediate environment that make impractical the collection of aerial images using standard airborne techniques. The methods provide high resolution stereo photos suitable for image processing and stereographic analysis; the images are potentially suitable for change analyses, velocity tracking, and construction of lidar-resolution digital elevation models. We developed two techniques. The technique suitable for small-scale features (such as gravel bars) utilizes two Nikon D3000 digital single-lens reflex (DSLR) cameras attached to a system of poles that suspends the cameras at a height of 4 meters with a variable camera separation of 0.6 to 0.9 m. The poles are oriented such that they do not appear in the photographs. The cameras are simultaneously remotely activated to collect stereo pairs at a resolution of 64 pixels/cm2 (pixel length is 1.2 mm). Ground control on the images is provided by pegs placed 5 meters apart, GPS positioning, and a meter-stick included in each photograph. Initial photo data gathered of a gravel bar on the Henrys Fork of the Snake River, north of Rexburg, Idaho is sharp and readily segmented using the MatLab-based CLASTS image processing algorithm. The technique developed for imaging mid-scale features (such as cinder cones) consists of a tethered weather balloon with a gimbal that keeps the camera oriented vertically. A single DSLR camera is suspended at an elevation of approximately 45 m. The camera is operated via a radio-controlled apparatus that enables the user to view the area being photographed prior to activating the shutter. The balloon is physically moved to capture the second image of the stereo pair. Resolution of the images is 3600 pixels/m2 (pixel length is 1.6 cm). The techniques demonstrate that collecting high-resolution stereographic aerial photographs can be accomplished on a limited budget. The techniques and equipment will be used to collect repeat images for several multi-year studies, including monitoring gravel bar evolution, vector tracking of landslide and rock glacier motion, and monitoring fault scarp and cinder cone degradation.

  12. Correlation between uterine fibroids with various magnetic resonance imaging features and therapeutic effects of high-intensity focused ultrasound ablation

    PubMed Central

    Cheng, Hailing; Wang, Chen; Tian, Jun

    2015-01-01

    Objective: To explore the correlation between magnetic resonance imaging (MRI) features of uterine fibroids (UFs) and therapeutic effects of high-intensity focused ultrasound ablation (HIFUA), and to provide evidence for UFs diagnosis with MRI in clinical practice. Methods: Forty-three UFs patients who were treated in our hospital from April 2012 to June 2014 were selected, including 72 UFs (48 multiple and 24 single UFs). Transverse, sagittal and coronal MRI scanning was performed one week before and after HIFUA to record UF number, location, type (intramural fibroid, submucosal fibroid and subserosal fibroid), mean diameter, hemoperfusion state, volume and ablation rate. The patients were followed up in the postoperative 1st, 2nd and 3rd months. Results: HIFUA exerted the best ablative effect on fibroids on the anterior uterine wall (F=26.763, P=0.036). Various types of fibroids were ablated significantly differently (F=3.406, P<0.05) by HIFUA that was most effective for ablating the subserosal ones. Having significantly different ablative effects on UFs with different radial line lengths (F=29.94, P<0.05), HIFUA ablated those with radial line lengths of 3-5 cm most effectively. For UFs with different T2WI signal intensities, HIFUA also functioned significantly differently (F=3.179, P=0. 03). Conclusion: HIFUA exerted significantly different ablative effects on UFs with various MRI features. Therefore, these features were well correlated with the therapeutic effects of HIFUA, allowing MRI as a promising diagnostic protocol. PMID:26430420

  13. Novel digital diffractive tags integrating anti-counterfeiting, tamper-evident, and high-density WORM data storage features

    NASA Astrophysics Data System (ADS)

    Boisdur, Enrick; Kress, Bernard

    2010-05-01

    Embossed holographic tags for security and anti-counterfeiting applications are being used by industry since many years. However, such elements are not very effective since the detector is usually the human eye, and provides therefore around 80% effective counterfeiting protection of the tag. We present a novel holographic anticounterfeiting technology which provides 99.999% protection against tag counterfeiting. Horus Technologies develops such holographic tags, which include several layers of increasingly secure optical features, from standard visual holographic patterns and OVIDs (Optical Variable Imaging Devices), to micro-holographic text, down to covert features such as encrypted high resolution holographic 1d, 2d and 3d bar codes. We also demonstrate the potential of providing anti-tamper functionality on the same tag, for packaging security (especially for medical packaging). Finally, we demonstrate that more than 1Mb/square mm of digital data can be stored and encrypted on these same tags. A specific low cost laser based reader is developed to read the various security feature of such hybrid universal holographic tags. We also present a way to change and update the encrypted data in the tag in a similar way to RFID tags. Finally, we show a cost effective technique to replicate these structures in volume by roll-to-toll embossing, and even direct by glass molding within the package itself (bottle, vial, etc,..).

  14. Features of primary damage by high energy displacement cascades in concentrated Ni-based alloys

    NASA Astrophysics Data System (ADS)

    Béland, Laurent Karim; Lu, Chenyang; Osetskiy, Yuri N.; Samolyuk, German D.; Caro, Alfredo; Wang, Lumin; Stoller, Roger E.

    2016-02-01

    Alloying of Ni with Fe or Co has been shown to reduce primary damage production under ion irradiation. Similar results have been obtained from classical molecular dynamics simulations of 1, 10, 20, and 40 keV collision cascades in Ni, NiFe, and NiCo. In all cases, a mix of imperfect stacking fault tetrahedra, faulted loops with a 1/3⟨111⟩ Burgers vector, and glissile interstitial loops with a 1/2⟨110⟩ Burgers vector were formed, along with small sessile point defect complexes and clusters. Primary damage reduction occurs by three mechanisms. First, Ni-Co, Ni-Fe, Co-Co, and Fe-Fe short-distance repulsive interactions are stiffer than Ni-Ni interactions, which lead to a decrease in damage formation during the transition from the supersonic ballistic regime to the sonic regime. This largely controls final defect production. Second, alloying decreases thermal conductivity, leading to a longer thermal spike lifetime. The associated annealing reduces final damage production. These two mechanisms are especially important at cascades energies less than 40 keV. Third, at the higher energies, the production of large defect clusters by subcascades is inhibited in the alloys. A number of challenges and limitations pertaining to predictive atomistic modeling of alloys under high-energy particle irradiation are discussed.

  15. High amplitude theta wave bursts: a novel electroencephalographic feature of rem sleep and cataplexy.

    PubMed

    Lo Martire, Viviana Carmen; Bastianini, Stefano; Berteotti, Chiara; Silvani, Alessandro; Zoccoli, Giovanna

    2015-09-01

    High amplitude theta wave bursts (HATs) were originally described during REMS and cataplexy in ORX-deficient mice as a novel neurophysiological correlate of narcolepsy (Bastianini et al., 2012). This finding was replicated the following year by Vassalli et al. in both ORX-deficient narcoleptic mice and narcoleptic children during cataplexy episodes (Vassalli et al., 2013). The relationship between HATs and narcolepsy-cataplexy in mice and patients indicates that the lack of ORX peptides is responsible for this abnormal EEG activity, the physiological meaning of which is still unknown. This review aimed to explore different phasic EEG events previously described in the published literature in order to find analogies and differences with HATs observed in narcoleptic mice and patients. We found similarities in terms of morphology, frequency and duration between HATs and several physiological (mu and wicket rhythms, sleep spindles, saw-tooth waves) or pathological (SWDs, HVSs, bursts of polyphasic complexes EEG complexes reported in a mouse model of CJD, and BSEs) EEG events. However, each of these events also shows significant differences from HATs, and thus cannot be equaled to them. The available evidence thus suggests that HATs are a novel neurophysiological phenomenon. Further investigations on HATs are required in order to investigate their physiological meaning, to individuate their brain structure(s) of origin, and to clarify the neural circuits involved in their manifestation. PMID:26742662

  16. Features of primary damage by high energy displacement cascades in concentrated Ni-based alloys

    DOE PAGESBeta

    Béland, Laurent Karim; Lu, Chenyang; Osetskiy, Yuri N.; Samolyuk, German D.; Caro, Alfredo; Wang, Lumin; Stoller, Roger E.

    2016-02-25

    Alloying of Ni with Fe or Co reduces primary damage production under ion irradiation. Similar results have been obtained from classical molecular dynamics simulations of 1, 10, 20, and 40 keV collision cascades in Ni, NiFe, and NiCo. In all cases, a mix of imperfect stacking fault tetrahedra, faulted loops with a 1/3 {111} Burgers vector, and glissile interstitial loops with a 1/2 {110} Burgers vector were formed, along with small sessile point defect complexes and clusters. Primary damage reduction occurs by three mechanisms. First, Ni-Co, Ni-Fe, Co-Co, and Fe-Fe short-distance repulsive interactions are stiffer than Ni-Ni interactions, which leadmore » to a decrease in damage formation during the transition from the supersonic ballistic regime to the sonic regime. This largely controls final defect production. Second, alloying decreases thermal conductivity, leading to a longer thermal spike lifetime. The associated annealing reduces final damage production. These two mechanisms are especially important at cascades energies less than 40 keV. Third, at the higher energies, the production of large defect clusters by subcascades is inhibited in the alloys. A number of challenges and limitations pertaining to predictive atomistic modeling of alloys under high-energy particle irradiation are discussed.« less

  17. Features of High-Temperature Calibration of W/Re Thermocouples

    NASA Astrophysics Data System (ADS)

    Ulanovskiy, A.; Edler, F.; Fischer, J.; Oleynikov, P.; Zaytsev, P.; Pokhodun, A.

    2015-03-01

    Investigations of Type A (W-5 %Re/W-20 %Re) thermocouples were performed at several laboratories to validate their reference function before its standardization in the new issue of the international standard IEC 60584. The Type A thermocouples investigated were equipped with sealed protection tubes made of sapphire which were filled with an inert gas (argon). The investigations at Russian laboratories were performed mainly in carbon-free high-temperature furnaces. The calibration results obtained in the temperature range (600 to 1850) in the carbon-free environment were within % tolerance limits and confirmed the suitability of Type A thermocouples for industrial applications. In contrast, the Type A thermocouple 89/95-P investigated at PTB (Germany) was exposed to a carbon environment when annealed at and when it was calibrated at metal-carbon eutectic (Me-C) fixed points. Measurements made at Me-C fixed points did not deviate from the reference function by more than about 6 K at the first stage when temperatures were below . However, the inhomogeneity of the thermoelements increased continuously after the calibration at the Me-C eutectic fixed points. The additional measurements at the peritectic fixed point () resulted in a continuous emf drift to deviations from the reference function of about (100 to 150) which corresponds to a temperature equivalent of about (9 to 14) K. The thermoelectric stability and homogeneity of the thermocouple 89/95-P during these investigations was checked by repeated measurements at the freezing point of copper ().

  18. Mitotic Asynchrony Induces Transforming Growth Factor-β1 Secretion from Airway Epithelium

    PubMed Central

    Alcala, Sarah E.; Benton, Angela S.; Watson, Alan M.; Kureshi, Suraiya; Reeves, Erica M. K.; Damsker, Jesse; Wang, Zuyi; Nagaraju, Kanneboyina; Anderson, Julia; Williams, Aaron M.; Lee, Amber J. Y.; Hayes, Kathleen; Rose, Mary C.; Hoffman, Eric P.

    2014-01-01

    We recently proposed that mitotic asynchrony in repairing tissue may underlie chronic inflammation and fibrosis, where immune cell infiltration is secondary to proinflammatory cross-talk among asynchronously repairing adjacent tissues. Building on our previous finding that mitotic asynchrony is associated with proinflammatory/fibrotic cytokine secretion (e.g., transforming growth factor [TGF]-β1), here we provide evidence supporting cause-and-effect. Under normal conditions, primary airway epithelial basal cell populations undergo mitosis synchronously and do not secrete proinflammatory or profibrotic cytokines. However, when pairs of nonasthmatic cultures were mitotically synchronized at 12 hours off-set and then combined, the mixed cell populations secreted elevated levels of TGF-β1. This shows that mitotic asynchrony is not only associated with but is also causative of TGF-β1 secretion. The secreted cytokines and other mediators from asthmatic cells were not the cause of asynchronous regeneration; synchronously mitotic nonasthmatic epithelia exposed to conditioned media from asthmatic cells did not show changes in mitotic synchrony. We also tested if resynchronization of regenerating asthmatic airway epithelia reduces TGF-β1 secretion and found that pulse-dosed dexamethasone, simvastatin, and aphidicolin were all effective. We therefore propose a new model for chronic inflammatory and fibrotic conditions where an underlying factor is mitotic asynchrony. PMID:24669775

  19. Cdk1 Inactivation Terminates Mitotic Checkpoint Surveillance and Stabilizes Kinetochore Attachments in Anaphase

    PubMed Central

    Vzquez-Novelle, MaraDolores; Sansregret, Laurent; Dick, AmalieE.; Smith, ChristopherA.; McAinsh, AndrewD.; Gerlich, DanielW.; Petronczki, Mark

    2014-01-01

    Summary Two mechanisms safeguard the bipolar attachment of chromosomes in mitosis. A correction mechanism destabilizes erroneous attachments that do not generate tension across sister kinetochores [1]. In response to unattached kinetochores, the mitotic checkpoint delays anaphase onset by inhibiting the anaphase-promoting complex/cyclosome (APC/CCdc20) [2]. Upon satisfaction of both pathways, the APC/CCdc20 elicits the degradation of securin and cyclin B [3]. This liberates separase triggering sister chromatid disjunction and inactivates cyclin-dependent kinase 1 (Cdk1) causing mitotic exit. How eukaryotic cells avoid the engagement of attachment monitoring mechanisms when sister chromatids split and tension is lost at anaphase is poorly understood [4]. Here we show that Cdk1 inactivation disables mitotic checkpoint surveillance at anaphase onset in human cells. Preventing cyclin B1 proteolysis at the time of sister chromatid disjunction destabilizes kinetochore-microtubule attachments and triggers the engagement of the mitotic checkpoint. As a consequence, mitotic checkpoint proteins accumulate at anaphase kinetochores, the APC/CCdc20 is inhibited, and securin reaccumulates. Conversely, acute pharmacological inhibition of Cdk1 abrogates the engagement and maintenance of the mitotic checkpoint upon microtubule depolymerization. We propose that the simultaneous destruction of securin and cyclin B elicited by the APC/CCdc20 couples chromosome segregation to the dissolution of attachment monitoring mechanisms during mitotic exit. PMID:24583019

  20. Temporal proteome profiling of taxol-induced mitotic arrest and apoptosis.

    PubMed

    Bull, Vibeke H; Fargestad, Ellen M; Strozynski, Margarita; Thiede, Bernd

    2010-06-01

    Taxol (Paclitaxel) is a mitotic inhibitor widely used in cancer therapy. Temporal proteome profiling was performed to study changes of proteins during the different cellular states of HeLa cells caused by exposure to taxol. The changes of proteins over time could be associated with various cellular processes such as mitotic arrest, an intermediate between mitotic arrest and apoptosis, apoptosis, and late apoptosis. Calumenin, stress-induced phosphoprotein 1 (STIP1), and translationally controlled tumor protein (TCTP) were assigned to mitotic arrest and selected for further experiments using immunoblotting and subcellular fractionation. Calumenin translocated from membranes to the cytosol during mitotic arrest and late apoptosis, but was significantly reduced in the cytosol during apoptosis. Translocation of STIP1 to the nucleus was observed at apoptosis and to the cytoskeleton at late apoptosis. TCTP increased in the cytosol at mitotic arrest and in membranes at apoptosis. In addition, the quantitative time courses of Bim isoforms revealed differences between BimL and BimS in comparison with BimEL. In summary, temporal proteome profiling of HeLa cells incubated with taxol allowed the assignment of proteins to certain processes and additional experiments with complementary approaches enabled a more comprehensive understanding of spatial changes of selected proteins during mitotic arrest and apoptosis. PMID:20506421

  1. Cdk1 inactivation terminates mitotic checkpoint surveillance and stabilizes kinetochore attachments in anaphase.

    PubMed

    Vzquez-Novelle, Mara Dolores; Sansregret, Laurent; Dick, Amalie E; Smith, Christopher A; McAinsh, Andrew D; Gerlich, Daniel W; Petronczki, Mark

    2014-03-17

    Two mechanisms safeguard the bipolar attachment of chromosomes in mitosis. A correction mechanism destabilizes erroneous attachments that do not generate tension across sister kinetochores [1]. In response to unattached kinetochores, the mitotic checkpoint delays anaphase onset by inhibiting the anaphase-promoting complex/cyclosome (APC/C(Cdc20)) [2]. Upon satisfaction of both pathways, the APC/C(Cdc20) elicits the degradation of securin and cyclin B [3]. This liberates separase triggering sister chromatid disjunction and inactivates cyclin-dependent kinase 1 (Cdk1) causing mitotic exit. How eukaryotic cells avoid the engagement of attachment monitoring mechanisms when sister chromatids split and tension is lost at anaphase is poorly understood [4]. Here we show that Cdk1 inactivation disables mitotic checkpoint surveillance at anaphase onset in human cells. Preventing cyclin B1 proteolysis at the time of sister chromatid disjunction destabilizes kinetochore-microtubule attachments and triggers the engagement of the mitotic checkpoint. As a consequence, mitotic checkpoint proteins accumulate at anaphase kinetochores, the APC/C(Cdc20) is inhibited, and securin reaccumulates. Conversely, acute pharmacological inhibition of Cdk1 abrogates the engagement and maintenance of the mitotic checkpoint upon microtubule depolymerization. We propose that the simultaneous destruction of securin and cyclin B elicited by the APC/C(Cdc20) couples chromosome segregation to the dissolution of attachment monitoring mechanisms during mitotic exit. PMID:24583019

  2. Features of Propagation of the Acoustic-Gravity Waves Generated by High-Power Periodic Radiation

    NASA Astrophysics Data System (ADS)

    Chernogor, L. F.; Frolov, V. L.

    2013-09-01

    We present the results of the bandpass filtering of temporal variations of the Doppler frequency shift of radio signals from a vertical-sounding Doppler radar located near the city of Kharkov when the ionosphere was heated by high-power periodic (with 10 and 15-min periods) radiation from the Sura facility. The filtering was done in the ranges of periods that are close to the acoustic cutoff period and the BruntVisl period (4-6, 8-12, and 13-17 min). Oscillations with periods of 4-6 min and amplitudes of 50-100 mHz were not recorded in fact. Oscillations with periods of 8-12 and 13-17 min and amplitudes of 60-100 mHz were detected in almost all the sessions. In the former and the latter oscillations, the time of delay with respect to the heater switch-on was close to 100 min and about 40-50 min, respectively. These values correspond to group propagation velocities of about 160 and 320-400 m/s. The Doppler shift oscillations were caused by the acoustic-gravity waves which led to periodic variations in the electron number density with a relative amplitude of about 0.1-1.0%. It was demonstrated that the acoustic-gravity waves were not recorded when the effective power of the Sura facility was equal to 50 MW and they were confidently observed when the effective power was increased up to 130 MW. It is shown that the period of the wave processes was determined by the period of the heating-pause cycles, and the duration of the wave trains did not depend on the duration of the series of heating-pause cycles. The data suggest that the generation mechanism of recorded wave disturbances is different from the mechanism proposed in 1970-1990.

  3. High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients with Primary Immunodeficiencies

    PubMed Central

    Driss, Nadia; Ben-Mustapha, Imen; Mellouli, Fethi; Ben Yahia, Ahlem; Touzi, Henda; Bejaoui, Mohamed; Ben Ghorbel, Mohamed; Barbouche, Mohamed-Ridha

    2012-01-01

    To estimate the susceptibility to enterovirus infection and the frequency of long-term poliovirus excreters in Tunisian patients with primary immunodeficiencies (PIDs), enteroviruses were assessed in stool specimens of 82 patients with humoral, combined, and other PIDs. Isolated viruses were typed and intratyped by standard molecular techniques, and the whole VP1 region of poliovirus isolates was sequenced. Polioviruses were detected in 6 patients; all isolates were vaccine related. Five patients rapidly stopped excretion; one excreted a poliovirus type 1 isolate for several months, and the isolate accumulated up to 14 mutations in the VP1 region. Nonpolio enteroviruses were identified in 6 patients; 4 of them kept excreting the same strain for more than 6 months. The rate of enterovirus infection was 13.4% of the PID patients and 20.7% of those with an IgG defect; it greatly exceeded the rates generally found in Tunisian supposed-immunocompetent individuals (4.1% during the study period; P = 0.001 and P < 0.0001, respectively). Interestingly, patients with combined immunodeficiencies were at a higher risk for enterovirus infection than those with an exclusively B cell defect. A major histocompatibility complex (MHC) class II antigen expression defect was found in 54% of enterovirus-positive patients and in the unique long-term poliovirus excreter. The study results also suggest that substitutive immunoglobulin therapy may help clearance of a poliovirus infection and that most PID patients have the ability to stop poliovirus excretion within a limited period. However, the high susceptibility of these patients to enterovirus infection reinforces the need for enhanced surveillance of these patients until the use of oral poliovirus vaccine (OPV) is stopped. PMID:22914367

  4. The Inner Nuclear Membrane Protein Src1 Is Required for Stable Post-Mitotic Progression into G1 in Aspergillus nidulans

    PubMed Central

    Osmani, Aysha H.; Osmani, Stephen A.

    2015-01-01

    How membranes and associated proteins of the nuclear envelope (NE) are assembled specifically and inclusively around segregated genomes during exit from mitosis is incompletely understood. Inner nuclear membrane (INM) proteins play key roles by providing links between DNA and the NE. In this study we have investigated the highly conserved INM protein Src1 in Aspergillus nidulans and have uncovered a novel cell cycle response during post mitotic formation of G1 nuclei. Live cell imaging indicates Src1 could have roles during mitotic exit as it preferentially locates to the NE abscission points during nucleokinesis and to the NE surrounding forming daughter G1 nuclei. Deletion analysis further supported this idea revealing that although Src1 is not required for interphase progression or mitosis it is required for stable post-mitotic G1 nuclear formation. This conclusion is based upon the observation that in the absence of Src1 newly formed G1 nuclei are structurally unstable and immediately undergo architectural modifications typical of mitosis. These changes include NPC modifications that stop nuclear transport as well as disassembly of nucleoli. More intriguingly, the newly generated G1 nuclei then cycle between mitotic- and interphase-like states. The findings indicate that defects in post-mitotic G1 nuclear formation caused by lack of Src1 promote repeated failed attempts to generate stable G1 nuclei. To explain this unexpected phenotype we suggest a type of regulation that promotes repetition of defective cell cycle transitions rather than preventing progression past the defective cell cycle transition. We suggest the term reboot regulation to define this mode of cell cycle regulation. The findings are discussed in relationship to recent studies showing the Cdk1 master oscillator can entrain subservient oscillators that when uncoupled cause cell cycle transitions to be repeated. PMID:26147902

  5. Concentration of elements in mitotic chromatin as measured by x-ray microanalysis

    PubMed Central

    1977-01-01

    Unfixed frozen-dried and uncoated tissue sections of the mouse duodenum were placed on carbon planchets and analyzed in a scanning electron microscope fitted with energy dispersive X-ray equipment. Computer analysis of the X-ray spectra allowed elemental microanalysis of the nucleus, cytoplasm, and mitotic chromatin regions in the cryptal and villus enterocytes. The peak to continuum ratio of S, Cl, K, and Ca were higher in mitotic chromatin than any of the other sites measured. The redistribution of Ca at mitosis is postulated to help explain both chromosome condensation and assembly of the mitotic spindle apparatus. PMID:856831

  6. Atomic Force Microscopy to Study Mechanics of Living Mitotic Mammalian Cells

    NASA Astrophysics Data System (ADS)

    Toyoda, Yusuke; Stewart, Martin P.; Hyman, Anthony A.; Müller, Daniel J.

    2011-08-01

    While biochemical pathways within mitotic cells have been intensively studied, the mechanics of dividing cells is only poorly understood. In our recent report, an experimental system combining fluorescence and atomic force microscopy was set up to study dynamics of mitotic rounding of mammalian cells. We show that cells have a rounding pressure that increases upon mitotic entry. Using specific inhibitors or perturbations, we revealed biological processes required for force generation that underpin the cell rounding shape change during mitosis. The significance of the finding and an outlook are discussed.

  7. High-risk angina patient. Identification by clinical features, hospital course, electrocardiography and technetium-99m stannous pyrophosphate scintigraphy

    SciTech Connect

    Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

    1981-10-01

    We evaluated 193 consecutive unstable angina patients by clinical features, hospital course and electrocardiography. All patients were managed medically. Of the 193 patients, 150 (78%) had a technetium-99m pyrophosphate (Tc-PYP) myocardial scintigram after hospitalization. Of these, 49 (33%) had positive scintigrams. At a follow-up of 24.9 +/- 10.8 months after hospitalization, 16 of 49 patients (33%) with positive scintigrams died from cardiac causes, compared with six of 101 patients (6%) with negative scintigrams (p less than 0.001). Of 49 patients with positive scintigrams, 11 (22%) had had nonfatal myocardial infarction at follow-up, compared with seven of 101 patients (7%) with negative scintigrams (p less than 0.01). Age, duration of clinical coronary artery disease, continuing angina during hospitalization, ischemic ECG, cardiomegaly and a history of heart failure also correlated with cardiac death at follow-up. Ischemic ECG and a history of angina with a crescendo pattern also correlated with nonfatal infarction at follow-up. Patients with continuing angina, an ischemic ECG and a positive scintigram constituted a high-risk unstable angina subgroup with a survival rate of 58% at 6 months, 47% at 12 months and 42% at 24 and 36 months. We conclude that the assessment of clinical features, hospital course, ECG and Tc-PYP scintigraphy may be useful in identifying high-risk unstable angina patients.

  8. High-risk angina patient: identification by clinical features, hospital course, electrocardiography, and technetium-99m stannous pyrophosphate scintigraphy

    SciTech Connect

    Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

    1981-10-01

    We evaluated 193 consecutive unstable angina patients by clinical features, hospital course and electrocardiography. All patients were managed medically. Of the 193 patients, 150 (78%) had a technetium-99m pyrophosphate (Tc-PYP) myocardial scintigram after hospitalization. Of these, 49 (33%) had positive scintigrams. At a follow-up of 24.9 +- 10.8 months after hospitalization, 16 of 49 patients (33%) with positive scintigrams died from cardiac causes, compared with six of 101 patients (6%) with negative scintigrams (p < 0.001). Of 49 patients with positive scintigrams, 11 (22%) had had nonfatal myocardial infarction at follow-up, compared with seven of 101 patients (7%) with negative scintigrams (p < 0.01). Age, duration of clinical coronary artery disease, continuing angina during hospitalization, ischemic ECG, cardiomegaly and a history of heart failure also correlated with cardiac death at follow-up. Ischemic ECG and a history of angina with a crescendo pattern also correlated with nonfatal infarction at follow-up. Patients with continuing angina, an ischemic ECG and a positive scintigram constituted a high-risk unstable angina subgroup, with a survival rate of 58% at 6 months, 47% at 12 months and 42% at 24 and 36 months. We conclude that the assessment of clinical features, hospital course, ECG and Tc-PYP scintigraphy may be useful in identifying high-risk unstable angina patients.

  9. Atmospheric-water absorption features near 2.2 micrometers and their importance in high spectral resolution remote sensing

    NASA Technical Reports Server (NTRS)

    Kruse, F. A.; Clark, R. N.

    1986-01-01

    Selective absorption of electromagnetic radiation by atmospheric gases and water vapor is an accepted fact in terrestrial remote sensing. Until recently, only a general knowledge of atmospheric effects was required for analysis of remote sensing data; however, with the advent of high spectral resolution imaging devices, detailed knowledge of atmospheric absorption bands has become increasingly important for accurate analysis. Detailed study of high spectral resolution aircraft data at the U.S. Geological Survey has disclosed narrow absorption features centered at approximately 2.17 and 2.20 micrometers not caused by surface mineralogy. Published atmospheric transmission spectra and atmospheric spectra derived using the LOWTRAN-5 computer model indicate that these absorption features are probably water vapor. Spectral modeling indicates that the effects of atmospheric absorption in this region are most pronounced in spectrally flat materials with only weak absorption bands. Without correction and detailed knowledge of the atmospheric effects, accurate mapping of surface mineralogy (particularly at low mineral concentrations) is not possible.

  10. High performance organic integrated device with ultraviolet photodetective and electroluminescent properties consisting of a charge-transfer-featured naphthalimide derivative

    SciTech Connect

    Wang, Hanyu; Wang, Xu; Yu, Junsheng E-mail: jsyu@uestc.edu.cn; Zhou, Jie; Lu, Zhiyun E-mail: jsyu@uestc.edu.cn

    2014-08-11

    A high performance organic integrated device (OID) with ultraviolet photodetective and electroluminescent (EL) properties was fabricated by using a charge-transfer-featured naphthalimide derivative of 6-(3,5-bis-[9-(4-t-butylphenyl)-9H-carbazol-3-yl]-phenoxy)-2- (4-t-butylphenyl)-benzo[de]isoquinoline-1,3-dione (CzPhONI) as the active layer. The results showed that the OID had a high detectivity of 1.5 × 10{sup 11} Jones at −3 V under the UV-350 nm illumination with an intensity of 0.6 mW/cm{sup 2}, and yielded an exciplex EL light emission with a maximum brightness of 1437 cd/m{sup 2}. Based on the energy band diagram, both the charge transfer feature of CzPhONI and matched energy level alignment were responsible for the dual ultraviolet photodetective and EL functions of OID.

  11. Mitotic Crossing over and Nondisjunction in Translocation Heterozygotes of Aspergillus

    PubMed Central

    Kfer, Etta

    1976-01-01

    To analyze mitotic recombination in translocation heterozygotes of A. nidulans two sets of well-marked diploids were constructed, homo- or heterozygous for the reciprocal translocations T1(IL;VIIR) or T2(IL;VIIIR) and heterozygous for selective markers on IL. It was found that from all translocation heterozygotes some of the expected mitotic crossover types could be selected. Such crossovers are monosomic for one translocated segment and trisomic for the other and recovery depends on the relative viabilities of these unbalanced types. The obtained segregants show characteristically reduced growth rates and conidiation dependent on sizes and types of mono- and trisomic segments, and all spontaneously produce normal diploid sectors. Such secondary diploid types either arose in one step of compensating crossing over in the other involved arm, ormore conspicuouslyin two steps of nondisjunction via a trisomic intermediate.In both of the analyzed translocations the segments translocated to IL were extremely long, while those translocated from IL were relatively short. The break in I for T1(I;VII) was located distal to the main selective marker in IL, while that of T2(I;VIII) had been mapped proximal but closely linked to it. Therefore, as expected, the selected primary crossover from the two diploids with T2( I;VIII) in coupling or in repulsion to the selective marker, showed the same chromosomal imbalance and poor growth. These could however be distinguished visually because they spontaneously produced different trisomic intermediates in the next step, in accordance with the different arrangement of the aneuploid segments. On the other hand, from diploids heterozygous for T1( I;VII) mitotic crossovers could only be selected when the selective markers were in coupling with the translocation; these crossovers were relatively well-growing and produced frequent secondary segregants of the expected trisomic, 2n+VII, type. For both translocations it was impossible to recover the reciprocal crossover types (which would be trisomic for the distal segments of I and monosomic for most of groups VII or VIII) presumably because these were too inviable to form conidia.In addition to the selected segregants of expected types a variety of unexpected ones were isolated. The conditions of selection used favour visual detection of aneuploid types, even if these produce only a few conidial heads and are not at a selective advantage. For T2(I;VIII) these "non-selected" unbalanced segregants were mainly "reciprocal" crossovers of the same phenotype and imbalance as the selected ones. For T1(I;VII) two quite different types were obtained, both possibly originating with loss of the small VIII translocation chromosome. One was isolated when the selective marker in repulsion to T1(I;VII) was used and, without being homo- or hemizygous for the selective marker, it produced stable sectors homozygous for this marker. The other was obtained from both coupling and repulsion diploids and showed a near-diploid genotype; it produced practically only haploid stable sectors of the type expected from monosomics, 2n1 for the short translocation chromosome. PMID:773747

  12. The tubulin-depolymerising agent combretastatin-4 induces ectopic aster assembly and mitotic catastrophe in lung cancer cells H460.

    PubMed

    Cenciarelli, Chiara; Tanzarella, Caterina; Vitale, Ilio; Pisano, Claudio; Crateri, Pasqualina; Meschini, Stefania; Arancia, Giuseppe; Antoccia, Antonio

    2008-05-01

    The relationship between microtubular dynamics, dismantling of pericentriolar components and induction of apoptosis was analysed after exposure of H460 non-small lung cancer cells to anti-mitotic drugs. The microtubule destabilising agent, combretastatin-A4 (CA-4) led to microtubular array disorganization, arrest in mitosis and abnormal metaphases, accompanied by the presence of numerous centrosome-independent "star-like" structures containing tubulin and aggregates of pericentrosomal matrix components like gamma-tubulin, pericentrin and ninein, whereas the structural integrity of centrioles was not affected by treatment. On the contrary, in condition of prolonged exposure or high concentrations of CA-4 such aggregates never formed. Treatment with 7.5 nM CA-4, which produced a high frequency "star-like" aggregates, was accompanied by mitotic catastrophe commitment characterized by translocation of the proapoptotic Bim protein to mitochondria activation of caspases-3/9 and DNA fragmentation as a result of either prolonged metaphase arrest or attempt of cells to divide. Drug concentrations which fail to block cells at mitosis were also unable to activate apotosis. A detailed time-course analysis of cell cycle arrest and apoptosis indicated that after CA-4 washout the number of metaphases with "star-like" structures decreased as a function of time and arrested cells proceeded in anaphase. After 4 h, the multiple alpha- and gamma-tubulin aggregates coalesced into two well-defined spindles in a bipolar mitotic spindle organization. Overall, our findings suggest that the maintenance of microtubular integrity plays a relevant role in stabilising the pericentriolar matrix, whose dismantling can be associated with apoptosis after exposure to microtubule depolymerising agents. PMID:18386182

  13. New spectral features of stratospheric trace gases identified from high-resolution infrared balloon-borne and laboratory spectra

    NASA Technical Reports Server (NTRS)

    Goldman, A.; Murcray, F. J.; Blatherwick, R. D.; Kosters, J. J.; Murcray, F. H.; Murcray, D. G.; Rinsland, C. P.

    1989-01-01

    A new Michelson-type interferometer system operating in the infrared at very high resolution has been used to record numerous balloon-borne solar absorption spectra of the stratosphere, ground-based solar absorption spectra, and laboratory spectra of molecules of atmospheric interest. In the present work results obtained for several important stratospheric trace gases, HNO3, CIONO2, HO2NO2, NO2, and COF2, in the 8- to 12-micron spectral region are reported. Many new features of these gases have been identified in the stratospheric spectra. Comparison of the new spectra with line-by-line simulations shows that previous spectral line parameters are often inadequate and that new analysis of high-resolution laboratory and atmospheric spectra and improved theoretical calculations will be required for many bands. Preliminary versions of several sets of improved line parameters under development are discussed.

  14. The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.

    PubMed

    Atwood, Craig S; Bowen, Richard L

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones that occur with menopause and during andropause are strongly correlated with neurodegeneration and cognitive decline. In this connection, much evidence now indicates that Alzheimer's disease (AD) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Here we review the biochemical, epidemiological and clinical evidence that alterations in sex hormone signaling associated with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle that leads to neurite retraction, neuron dysfunction and neuron death. When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex steroid ratio as driving aberrant mitotic events. These include the upregulation of tumor necrosis factor; amyloid-β precursor protein processing towards the production of mitogenic Aβ; and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex steroid ratio on dendritic spine density and human cognitive performance. Prospective epidemiological and clinical evidence in humans supports the premise that rebalancing the ratio of circulating gonadotropins:sex steroids reduces the incidence of AD. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson's disease. PMID:26188949

  15. The FlyCatwalk: a high-throughput feature-based sorting system for artificial selection in Drosophila.

    PubMed

    Medici, Vasco; Vonesch, Sibylle Chantal; Fry, Steven N; Hafen, Ernst

    2015-03-01

    Experimental evolution is a powerful tool for investigating complex traits. Artificial selection can be applied for a specific trait and the resulting phenotypically divergent populations pool-sequenced to identify alleles that occur at substantially different frequencies in the extreme populations. To maximize the proportion of loci that are causal to the phenotype among all enriched loci, population size and number of replicates need to be high. These requirements have, in fact, limited evolution studies in higher organisms, where the time investment required for phenotyping is often prohibitive for large-scale studies. Animal size is a highly multigenic trait that remains poorly understood, and an experimental evolution approach may thus aid in gaining new insights into the genetic basis of this trait. To this end, we developed the FlyCatwalk, a fully automated, high-throughput system to sort live fruit flies (Drosophila melanogaster) based on morphometric traits. With the FlyCatwalk, we can detect gender and quantify body and wing morphology parameters at a four-old higher throughput compared with manual processing. The phenotyping results acquired using the FlyCatwalk correlate well with those obtained using the standard manual procedure. We demonstrate that an automated, high-throughput, feature-based sorting system is able to avoid previous limitations in population size and replicate numbers. Our approach can likewise be applied for a variety of traits and experimental settings that require high-throughput phenotyping. PMID:25556112

  16. The FlyCatwalk: A High-Throughput Feature-Based Sorting System for Artificial Selection in Drosophila

    PubMed Central

    Medici, Vasco; Vonesch, Sibylle Chantal; Fry, Steven N.; Hafen, Ernst

    2015-01-01

    Experimental evolution is a powerful tool for investigating complex traits. Artificial selection can be applied for a specific trait and the resulting phenotypically divergent populations pool-sequenced to identify alleles that occur at substantially different frequencies in the extreme populations. To maximize the proportion of loci that are causal to the phenotype among all enriched loci, population size and number of replicates need to be high. These requirements have, in fact, limited evolution studies in higher organisms, where the time investment required for phenotyping is often prohibitive for large-scale studies. Animal size is a highly multigenic trait that remains poorly understood, and an experimental evolution approach may thus aid in gaining new insights into the genetic basis of this trait. To this end, we developed the FlyCatwalk, a fully automated, high-throughput system to sort live fruit flies (Drosophila melanogaster) based on morphometric traits. With the FlyCatwalk, we can detect gender and quantify body and wing morphology parameters at a four-old higher throughput compared with manual processing. The phenotyping results acquired using the FlyCatwalk correlate well with those obtained using the standard manual procedure. We demonstrate that an automated, high-throughput, feature-based sorting system is able to avoid previous limitations in population size and replicate numbers. Our approach can likewise be applied for a variety of traits and experimental settings that require high-throughput phenotyping. PMID:25556112

  17. The NOXA–MCL1–BIM axis defines lifespan on extended mitotic arrest

    PubMed Central

    Haschka, Manuel D.; Soratroi, Claudia; Kirschnek, Susanne; Häcker, Georg; Hilbe, Richard; Geley, Stephan; Villunger, Andreas; Fava, Luca L.

    2015-01-01

    Cell death on extended mitotic arrest is considered arguably most critical for the efficacy of microtubule-targeting agents (MTAs) in anticancer therapy. While the molecular machinery controlling mitotic arrest on MTA treatment, the spindle assembly checkpoint (SAC), appears well defined, the molecular components executing cell death, as well as factors connecting both networks remain poorly understood. Here we conduct a mini screen exploring systematically the contribution of individual BCL2 family proteins at single cell resolution to death on extended mitotic arrest, and demonstrate that the mitotic phosphorylation of BCL2 and BCLX represent a priming event for apoptosis that is ultimately triggered by NOXA-dependent MCL1 degradation, enabling BIM-dependent cell death. Our findings provide a comprehensive model for the initiation of apoptosis in cells stalled in mitosis and provide a molecular basis for the increased efficacy of combinatorial treatment of cancer cells using MTAs and BH3 mimetics. PMID:25922916

  18. Inhibition of a Mitotic Motor Protein: Where, How, and Conformational Consequences

    SciTech Connect

    Yan, Youwei; Sardana, Vinod; Xu, Bei; Homnick, Carl; Halczenko, Wasyl; Buser, Carolyn A.; Schaber, Michael; Hartman, George D.; Huber, Hans E.; Kuo, Lawrence C.

    2010-11-16

    We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 {angstrom} resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg{sup 2+} {center_dot} ADP, reveals that monastrol confers inhibition by 'induced-fitting' onto the protein some 12 {angstrom} away from the catalytic center of the enzyme, resulting in the creation of a previously non-existing binding pocket. The structure provides new insights into the biochemical and mechanical mechanisms of the mitotic motor domain. Inhibition of KSP provides a novel mechanism to arrest mitotic spindle formation, a target of several approved and investigative anti-cancer agents. The structural information gleaned from this novel pocket offers a new angle for the design of anti-mitotic agents.

  19. Association of Chromosome Loss with Centromere-Adjacent Mitotic Recombination in a Yeast Disomic Haploid

    PubMed Central

    Campbell, D. A.; Fogel, S.

    1977-01-01

    Experiments designed to characterize the association between disomic chromosome loss and centromere-adjacent mitotic recombination were performed. Mitotic gene convertants were selected at two heteroallelic sites on the left arm of disomic chromosome III and tested for coincident chromosome loss. The principal results are: (1) Disomic chromosome loss is markedly enhanced (nearly 40-fold) over basal levels among mitotic gene convertants selected to arise close to the centromere; no such enhancement is observed among convertants selected to arise relatively far from the centromere. (2) Chromosome loss is primarily associated with proximal allele conversion at the centromere-adjacent site, and many of these convertants are reciprocally recombined in the adjacent proximal interval. (3) Partial aneuploid exceptions provisionally identified as carrying left arm telocentrics have been found. A testable model is proposed suggesting that centromere involvement in genetic recombination may precipitate segregational disfunction leading to mitotic chromosome loss. PMID:324869

  20. The NOXA-MCL1-BIM axis defines lifespan on extended mitotic arrest.

    PubMed

    Haschka, Manuel D; Soratroi, Claudia; Kirschnek, Susanne; Hcker, Georg; Hilbe, Richard; Geley, Stephan; Villunger, Andreas; Fava, Luca L

    2015-01-01

    Cell death on extended mitotic arrest is considered arguably most critical for the efficacy of microtubule-targeting agents (MTAs) in anticancer therapy. While the molecular machinery controlling mitotic arrest on MTA treatment, the spindle assembly checkpoint (SAC), appears well defined, the molecular components executing cell death, as well as factors connecting both networks remain poorly understood. Here we conduct a mini screen exploring systematically the contribution of individual BCL2 family proteins at single cell resolution to death on extended mitotic arrest, and demonstrate that the mitotic phosphorylation of BCL2 and BCLX represent a priming event for apoptosis that is ultimately triggered by NOXA-dependent MCL1 degradation, enabling BIM-dependent cell death. Our findings provide a comprehensive model for the initiation of apoptosis in cells stalled in mitosis and provide a molecular basis for the increased efficacy of combinatorial treatment of cancer cells using MTAs and BH3 mimetics. PMID:25922916

  1. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair.

    PubMed

    Xia, Jingjing; Swiercz, Jakub M; Ban-Rodrguez, Inmaculada; Matkovi?, Ivana; Federico, Giuseppina; Sun, Tianliang; Franz, Timo; Brakebusch, Cord H; Kumanogoh, Atsushi; Friedel, Roland H; Martn-Belmonte, Fernando; Grne, Hermann-Josef; Offermanns, Stefan; Worzfeld, Thomas

    2015-05-01

    Morphogenesis, homeostasis, and regeneration of epithelial tissues rely on the accurate orientation of cell divisions, which is specified by the mitotic spindle axis. To remain in the epithelial plane, symmetrically dividing epithelial cells align their mitotic spindle axis with the plane. Here, we show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central regulatory mechanism of mitotic spindle orientation necessary for the alignment of epithelial cell divisions with the epithelial plane. PMID:25892012

  2. Dimerization of TRAF-interacting protein (TRAIP) regulates the mitotic progression.

    PubMed

    Park, I Seul; Jo, Ku-Sung; Won, Hyung-Sik; Kim, Hongtae

    2015-08-01

    The homo- or hetero-dimerization of proteins plays critical roles in the mitotic progression. The TRAF-interacting protein (TRAIP) is crucial in early mitotic progression and chromosome alignment defects in the metaphase. The TRAIP is a 469 amino acid protein, including the Really Interesting New Gene (RING), coiled-coil (CC), and leucine zipper (LZ) domain. In general, the CC or LZ domain containing proteins forms homo- or hetero-dimerization to achieve its activity. In this study, a number of TRAIP mutants were used to define the TRAIP molecular domains responsible for its homo-dimerization. A co-immunoprecipitation assay indicated that the TRAIP forms homo-dimerization through the CC domain. The cells, expressing the CC domain-deleted mutant that could not form a homo-dimer, increased the mitotic index and promoted mitotic progression. PMID:26093298

  3. Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size.

    PubMed

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk C; Lai, Fan; Niswander, Lee

    2014-01-01

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly. PMID:24875059

  4. Microcephaly Disease Gene Wdr62 Regulates Mitotic Progression of Embryonic Neural Stem Cells and Brain Size

    PubMed Central

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk; Lai, Fan; Niswander, Lee

    2014-01-01

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly. PMID:24875059

  5. High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

    PubMed Central

    Wang, Ke; Li, Dan; Sun, Lu

    2016-01-01

    Purpose The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. Methods Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. Results EGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. Conclusion High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID:26855586

  6. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae.

    PubMed

    Spencer, F; Gerring, S L; Connelly, C; Hieter, P

    1990-02-01

    We have isolated 136 independent mutations in haploid yeast strains that exhibit decreased chromosome transmission fidelity in mitosis. Eighty-five percent of the mutations are recessive and 15% are partially dominant. Complementation analysis between MATa and MAT alpha isolates identifies 11 chromosome transmission fidelity (CTF) complementation groups, the largest of which is identical to CHL1. For 49 independent mutations, no corresponding allele has been recovered in the opposite mating type. The initial screen monitored the stability of a centromere-linked color marker on a nonessential yeast chromosome fragment; the mitotic inheritance of natural yeast chromosome III is also affected by the ctf mutations. Of the 136 isolates identified, seven were inviable at 37 degrees and five were inviable at 11 degrees. In all cases tested, these temperature conditional lethalities cosegregated with the chromosome instability phenotype. Five additional complementation groups (ctf12 through ctf16) have been defined by complementation analysis of the mutations causing inviability at 37 degrees. Twenty-three of the 136 isolates exhibited growth defects at concentrations of benomyl permissive for the parent strain, and nine appeared to be tolerant of inhibitory levels of benomyl. All of the mutant strains showed normal sensitivity to ultraviolet and gamma-irradiation. Further characterization of these mutant strains will describe the functions of gene products crucial to the successful execution of processes required for aspects of the chromosome cycle that are important for chromosome transmission fidelity in mitosis. PMID:2407610

  7. Physical Description of Mitotic Spindle Orientation During Cell Division

    NASA Astrophysics Data System (ADS)

    Jimnez-Dalmaroni, Andrea; Thry, Manuel; Racine, Victor; Bornens, Michel; Jlicher, Frank

    2009-03-01

    During cell division, the duplicated chromosomes are physically separated by the action of the mitotic spindle. The spindle is a dynamic structure of the cytoskeleton, which consists of two microtubule asters. Its orientation defines the axis along which the cell divides. Recent experiments show that the spindle orientation depends on the spatial distribution of cell adhesion sites. Here we show that the experimentally observed spindle orientation can be understood as the result of the action of cortical force generators acting on the spindle. We assume that the local activity of force generators is controlled by the spatial distribution of cell adhesion sites determined by the particular geometry of the adhesive substrate. We develop a simple physical description of the spindle mechanics, which allows us to calculate the torque acting on the spindle, as well as the energy profile and the angular distribution of spindle orientation. Our model accounts for the preferred spindle orientation, as well as the full shape of the angular distributions of spindle orientation observed in a large variety of pattern geometries. M. Th'ery, A. Jim'enez-Dalmaroni, et al., Nature 447, 493 (2007).

  8. Phosphorylation and disassembly of intermediate filaments in mitotic cells

    SciTech Connect

    Chou, Yinghao; Rosevear, E.; Goldman, R.D. )

    1989-03-01

    As baby hamster kidney (BHK-21) cells enter mitosis, networks of intermediate filaments (IFs) are transformed into cytoplasmic aggregates of protofilaments. Coincident with this morphological change, the phosphate content of vimentin increases from 0.3 mol of P{sub i} per mol of protein in interphase to 1.9 mol of P{sub i} per mol of protein in mitosis. A similar increase in phosphate content is observed with desmin, from 0.5 mol of P{sub i} per mol of protein to 1.5 mol of P{sub i} per mol of protein. Fractionation of mitotic cell lysates by hydroxylapatite column chromatography reveals the presence of two IF protein kinase activities, designated as IF protein kinase I and IF protein kinase II. Comparison of two-dimensional {sup 32}P-labeled phosphopeptide maps of vimentin and desmin phosphorylated in vivo in mitosis, and in vitro using partially purified kinase fractions, reveals extensive similarity in the two sets of phosphorylation sites. Phosphorylation of in vitro polymerized IFs by IF protein kinase II induces complete disassembly as determined by negative-stain electron microscopy. The results support the idea that the disassembly of IFs in mitosis is regulated by the phosphorylation of its subunit proteins.

  9. Mitotic chromosome transmission fidelity mutants in Saccharomyces cerevisiae

    SciTech Connect

    Spencer, F.; Gerring, S.L.; Connelly, C.; Hieter, P. )

    1990-02-01

    The authors have isolated 136 independent EMS-induced mutations in haploid yeast strains that exhibit decreased chromosome transmission fidelity in mitosis. Eight-five percent of the mutations are recessive and 15% are partially dominant. Complementation analysis between MATa and MAT{alpha} isolates identifies 11 chromosome transmission fidelity (CTF) complementation groups, the largest of which is identical to CHL1. For 49 independent mutations, no corresponding allele has been recovered in the opposite mating type. The initial screen monitored the stability of a centromere-linked color marker on a nonessential yeast chromosome fragment; the mitotic inheritance of natural yeast chromosome III is also affected by the ctf mutations. Of the 136 isolates identified, seven were inviable at 37{degree} and five were inviable at 11{degree}. In all cases tested, these temperature conditional lethalities cosegregated with the chromosome instability phenotype. Five additional complementation groups (ctf12 through ctf16) have been defined by complementation analysis of the mutations causing inviability at 37{degree}. All of the mutant strains showed normal sensitivity to ultraviolet and {gamma}-irradiation.

  10. Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm

    PubMed Central

    Daniels, Brian R.; Rikhy, Richa; Renz, Malte; Dobrowsky, Terrence M.; Lippincott-Schwartz, Jennifer

    2012-01-01

    Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional compartmentalization has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial Drosophila embryo on the effective diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of transient mitotic membrane furrows results in a multiscale diffusion effect that has a significant impact on effective diffusion rates across the embryo. Using a combination of live-cell experiments and computational modeling, we characterize these effects and relate effective bulk diffusion rates to instantaneous diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of the early embryo. This multiscale effect may be related to the effect of interphase nuclei on effective diffusion, and thus we propose that an as-yet-unidentified role of syncytial membrane furrows is to temporally regulate bulk embryonic diffusion rates to balance the multiscale effect of interphase nuclei, which ultimately stabilizes the shapes of various morphogen gradients. PMID:22592793

  11. High-Resolution PFPE-based Molding Techniques for Nanofabrication of High-Pattern Density, Sub-20 nm Features: A Fundamental Materials Approach

    SciTech Connect

    Williams, Stuart S.; Retterer, Scott; Lopez, Rene; Ruiz, Ricardo; Samulski, Edward T.; DeSimone, Joseph M.

    2010-04-14

    Several perfluoropolyether (PFPE)-based elastomers for high-resolution replica molding applications are explored. The modulus of the elastomeric materials was increased through synthetic and additive approaches while maintaining relatively low surface tension values (<25 mN/m). Using large area (>4 in.{sup 2}) master templates, we experimentally show the relationship between mold resolution and material properties such as modulus and surface tension for materials used in this study. A composite mold approach was used to form flexible molds out of stiff, high modulus materials that allow for replication of sub-20 nm post structures. Sub-100 nm line grating master templates, formed using e-beam lithography, were used to determine the experimental stability of the molding materials. It was observed that as the feature spacing decreased, high modulus PFPE tetramethacrylate (TMA) composite molds were able to effectively replicate the nanograting structures without cracking or tear-out defects that typically occur with high modulus elastomers.

  12. High-grade gliomas in children.

    PubMed

    Cage, Tene A; Mueller, Sabine; Haas-Kogan, Daphne; Gupta, Nalin

    2012-07-01

    High-grade gliomas (HGGs) are malignant tumors and typically include glioblastoma multiforme and anaplastic astrocytoma subtypes. Brainstem gliomas and ependymomas are separate entities with respect to clinical presentation, treatment, prognosis, and outcome in comparison with supratentorial HGGs. In children, these tumors account for 3% to 7% of newly diagnosed brain tumors and 20% of all diagnoses of pediatric supratentorial brain tumors. These neoplasms are highly proliferative and mitotically active and of glial origin. This article reviews clinical, diagnostic, and pathologic features of HGG and current treatments and potential future therapies specific to pediatric patients with HGGs. PMID:22748663

  13. Segregation of recessive phenotypes in somatic cell hybrids role of mitotic recombination, gene inactivation, and chromosome nondisjunction

    SciTech Connect

    Campbell, C.E.; Worton, R.G.

    1981-04-01

    Somatic cell hybrids heterozygous at the emetine resistance locus (emt/sup r//emt/sup +/) or the chromate resistance locus (chr/sup r//chr/sup +/) are known to segregate the recessive drug resistance phenotype at high frequency. The authors have examined mechanisms of segregation in Chinese hamster cell hybrids heterozygous at these two loci, both of which map to the long arm of Chinese hamster chromosome 2. To allow the fate of chromosomal arms through the segregation process, our hybrids were also heterozygous at the mtx (methotrexate resistance) locus on the short arm of chromosome 2 and carried cytogenetically marked chromosomes with either a short-arm deletion 2p/sup -/) or a long-arm addition (2q/sup +/). Karotype and phenotype analysis of emetine- or chromate-resistant segregants from such hybrids allowed us to distinguish four potential segregation mechanisms: (i) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome; (ii) mitotic recombination between the centromere and the emt or chr loci giving rise to homozygous resistant segregants; (iii) inactivation of the emt/sup +/ or chr/sup +/ alleles; and (iv) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome with duplication of the homologous chromosome carrying the emt/sup r/ or chr/sup r/ allele. Of 48 independent segregants examined, only 9 (20%) arose by simple chromosome loss. Two segregants (4%) were consistent with a gene inactivation mechanism, but because of their rarity, other mechanisms such as mutation or submicroscopic deletion could not be excluded. Twenty-one segregants (44%) arose by either mitotic recombination or chromosome loss and duplication; the two mechanisms were not distinguishable in that experiment. Finally, in hybrids allowing these two mechanisms to be distinguished, 15 segregants (31%) arose by chromosome loss and duplication, and none arose by mitotic recombination.

  14. Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases.

    PubMed

    Matsuhashi, A; Ohno, T; Kimura, M; Hara, A; Saio, M; Nagano, A; Kawai, G; Saitou, M; Takigami, I; Yamada, K; Okano, Y; Shimizu, K

    2012-07-01

    Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, endoreduplication, and apoptosis. In the present study, we further investigated the molecular mechanisms underlying these effects. The inhibitor arrested various cells at G2 phase at low concentration, and at both G1 and G2 phases at high concentration. JNJ-7706621 did not prevent localization of Aurora A to the spindle poles, but did inhibit other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase. Similarly, the drug did not prevent localization of Aurora B to the kinetochore, but did inhibit other chromosomal passenger proteins such as Survivin and INCENP. In the cells exposed to JNJ-7706621 after nocodazole release, Aurora B, INCENP, and Survivin became relocated to the peripheral region of chromosomes, but Plk1 and Prc1 were localized on microtubules in later mitotic phase. Treatment of nocodazole-synchronized cells with JNJ-7706621 was able to override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation. Injection of the drug significantly inhibited the growth of TC135 Ewing's sarcoma cells transplanted into athymic mice by cell cycle arrest and apoptosis. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at multiple points, suggesting that it could be useful for cell cycle analysis and therapy of various cancers, including Ewing's sarcoma. PMID:22463590

  15. Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B.

    PubMed

    Akba?, H; Yalcin, K; Isi, H; Tekes, S; Atay, A E; Akkus, Z; Budak, T

    2012-11-01

    Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals. PMID:22892830

  16. High resolution transmission electron microscope Imaging and first-principles simulations of atomic-scale features in graphene membrane

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Bhandari, Sagar; Yi, Wei; Bell, David; Westervelt, Robert; Kaxiras, Efthimios

    2012-02-01

    Ultra-thin membranes such as graphene[1] are of great importance for basic science and technology applications. Graphene sets the ultimate limit of thinness, demonstrating that a free-standing single atomic layer not only exists but can be extremely stable and strong [2--4]. However, both theory [5, 6] and experiments [3, 7] suggest that the existence of graphene relies on intrinsic ripples that suppress the long-wavelength thermal fluctuations which otherwise spontaneously destroy long range order in a two dimensional system. Here we show direct imaging of the atomic features in graphene including the ripples resolved using monochromatic aberration-corrected transmission electron microscopy (TEM). We compare the images observed in TEM with simulated images based on an accurate first-principles total potential. We show that these atomic scale features can be mapped through accurate first-principles simulations into high resolution TEM contrast. [1] Geim, A. K. & Novoselov, K. S. Nat. Mater. 6, 183-191, (2007). [2] Novoselov, K. S.et al. Science 306, 666-669, (2004). [3] Meyer, J. C. et al. Nature 446, 60-63, (2007). [4] Lee, C., Wei, X. D., Kysar, J. W. & Hone, J. Science 321, 385-388, (2008). [5] Nelson, D. R. & Peliti, L. J Phys-Paris 48, 1085-1092, (1987). [6] Fasolino, A., Los, J. H. & Katsnelson, M. I. Nat. Mater. 6, 858-861, (2007). [7] Meyer, J. C. et al. Solid State Commun. 143, 101-109, (2007).

  17. Local changes of work function near rough features on Cu surfaces operated under high external electric field

    SciTech Connect

    Djurabekova, Flyura Ruzibaev, Avaz; Parviainen, Stefan; Holmström, Eero; Hakala, Mikko

    2013-12-28

    Metal surfaces operated under high electric fields produce sparks even if they are held in ultra high vacuum. In spite of extensive research on the topic of vacuum arcs, the mystery of vacuum arc origin still remains unresolved. The indications that the sparking rates depend on the material motivate the research on surface response to extremely high external electric fields. In this work by means of density-functional theory calculations we analyze the redistribution of electron density on (100) Cu surfaces due to self-adatoms and in presence of high electric fields from −1 V/nm up to −2 V/nm (−1 to −2 GV/m, respectively). We also calculate the partial charge induced by the external field on a single adatom and a cluster of two adatoms in order to obtain reliable information on charge redistribution on surface atoms, which can serve as a benchmarking quantity for the assessment of the electric field effects on metal surfaces by means of molecular dynamics simulations. Furthermore, we investigate the modifications of work function around rough surface features, such as step edges and self-adatoms.

  18. Inhibitors of Phosphatidylinositol 3?-Kinases Promote Mitotic Cell Death in HeLa Cells

    PubMed Central

    Huang, Yun; Yi, Qiyi; Lv, Lei; Zhang, Tianwei; Chen, Dawei; Hao, Qiaomei; Shi, Qinghua

    2012-01-01

    The phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in many biological processes, including cell cycle progression, cell growth, survival, actin rearrangement and migration, and intracellular vesicular transport. However, the involvement of the PI3K pathway in the regulation of mitotic cell death remains unclear. In this study, we treated HeLa cells with the PI3K inhibitors, 3-methyladenine (3-MA, as well as a widely used autophagy inhibitor) and wortmannin to examine their effects on cell fates using live cell imaging. Treatment with 3-MA decreased cell viability in a time- and dose-dependent manner and was associated with caspase-3 activation. Interestingly, 3-MA-induced cell death was not affected by RNA interference-mediated knockdown (KD) of beclin1 (an essential protein for autophagy) in HeLa cells, or by deletion of atg5 (an essential autophagy gene) in mouse embryonic fibroblasts (MEFs). These data indicate that cell death induced by 3-MA occurs independently of its ability to inhibit autophagy. The results from live cell imaging studies showed that the inhibition of PI3Ks increased the occurrence of lagging chromosomes and cell cycle arrest and cell death in prometaphase. Furthermore, PI3K inhibitors promoted nocodazole-induced mitotic cell death and reduced mitotic slippage. Overexpression of Akt (the downstream target of PI3K) antagonized PI3K inhibitor-induced mitotic cell death and promoted nocodazole-induced mitotic slippage. These results suggest a novel role for the PI3K pathway in regulating mitotic progression and preventing mitotic cell death and provide justification for the use of PI3K inhibitors in combination with anti-mitotic drugs to combat cancer. PMID:22545128

  19. Identifying Chinese Microblog Users With High Suicide Probability Using Internet-Based Profile and Linguistic Features: Classification Model

    PubMed Central

    Guan, Li; Hao, Bibo; Cheng, Qijin; Yip, Paul SF

    2015-01-01

    Background Traditional offline assessment of suicide probability is time consuming and difficult in convincing at-risk individuals to participate. Identifying individuals with high suicide probability through online social media has an advantage in its efficiency and potential to reach out to hidden individuals, yet little research has been focused on this specific field. Objective The objective of this study was to apply two classification models, Simple Logistic Regression (SLR) and Random Forest (RF), to examine the feasibility and effectiveness of identifying high suicide possibility microblog users in China through profile and linguistic features extracted from Internet-based data. Methods There were nine hundred and nine Chinese microblog users that completed an Internet survey, and those scoring one SD above the mean of the total Suicide Probability Scale (SPS) score, as well as one SD above the mean in each of the four subscale scores in the participant sample were labeled as high-risk individuals, respectively. Profile and linguistic features were fed into two machine learning algorithms (SLR and RF) to train the model that aims to identify high-risk individuals in general suicide probability and in its four dimensions. Models were trained and then tested by 5-fold cross validation; in which both training set and test set were generated under the stratified random sampling rule from the whole sample. There were three classic performance metrics (Precision, Recall, F1 measure) and a specifically defined metric “Screening Efficiency” that were adopted to evaluate model effectiveness. Results Classification performance was generally matched between SLR and RF. Given the best performance of the classification models, we were able to retrieve over 70% of the labeled high-risk individuals in overall suicide probability as well as in the four dimensions. Screening Efficiency of most models varied from 1/4 to 1/2. Precision of the models was generally below 30%. Conclusions Individuals in China with high suicide probability are recognizable by profile and text-based information from microblogs. Although there is still much space to improve the performance of classification models in the future, this study may shed light on preliminary screening of risky individuals via machine learning algorithms, which can work side-by-side with expert scrutiny to increase efficiency in large-scale-surveillance of suicide probability from online social media. PMID:26543921

  20. MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.

    PubMed

    Voets, Erik; Wolthuis, Rob M F

    2010-09-01

    Greatwall (Gwl) was originally discovered in Drosophila as an essential kinase for correct chromosome condensation and mitotic progression. In Xenopus, Gwl may influence the positive-feedback loop that directs cyclin B1-Cdk1 activation and the mitotic state by inhibiting the phosphatase PP 2A. Here, we describe the human orthologue of Gwl called microtubule-associated serine/threonine kinase-like (MASTL). We found that MASTL localizes to the nucleus in interphase and re-localizes in part to centrosomes in mitosis, when it is active. Cells strongly depleted of MASTL by RNAi delay in G(2) phase and reveal slow chromosome condensation. MASTL RNAi cells that enter and progress through mitosis often fail to completely separate their sister chromatids in anaphase. This causes chromatin to be trapped in the cleavage furrow, which may lead to the formation of 4N G(1) cells by cytokinesis failure. Further, our experiments indicate that MASTL supports the phosphorylation state of mitotic phospho-proteins downstream of cyclin B1-Cdk1, including the APC/C. Cyclin B1 destruction is incomplete when mitotic cells that are strongly depleted of MASTL exit mitosis. We propose that MASTL enhances cyclin B1-Cdk1-dependent mitotic phosphorylation events, directing mitotic entry, anaphase and cytokinesis in human cells. PMID:20818157

  1. Sli15INCENP Dephosphorylation Prevents Mitotic Checkpoint Reengagement Due to Loss of Tension at Anaphase Onset

    PubMed Central

    Mirchenko, Lesia; Uhlmann, Frank

    2010-01-01

    Summary The mitotic checkpoint, also known as the spindle assembly checkpoint, delays anaphase onset until all chromosomes have reached bipolar tension on the mitotic spindle [13]. Once this is achieved, the protease separase is activated to cleave the chromosomal cohesin complex, thereby triggering anaphase. Cohesin cleavage releases tension between sister chromatids, but why the mitotic checkpoint now remains silent is poorly understood. Here, using budding yeast as a model, we show that loss of sister chromatid cohesion at anaphase onset would engage the mitotic checkpoint if this was not prevented by concomitant separase-dependent activation of the Cdc14 phosphatase. Cdc14, in turn, inactivates the mitotic checkpoint by dephosphorylating Sli15INCENP, a subunit of the conserved Aurora B kinase complex that forms part of the proposed chromosomal tension sensor. Dephosphorylation-dependent relocation of Sli15INCENP from centromeres to the central spindle during anaphase is seen in organisms from yeast to human [48]. Our results suggest that Sli15INCENP dephosphorylation is part of an evolutionarily conserved mechanism that prevents the mitotic checkpoint from reengaging when tension between sister chromatids is lost at anaphase onset. PMID:20619650

  2. Substrate degradation by the anaphase promoting complex occurs during mitotic slippage

    PubMed Central

    Lee, Jinho; Kim, Jin Ah; Margolis, Robert L.; Fotedar, Rati

    2011-01-01

    Microtubule targeting drugs are successful in chemotherapy because they indefinitely activate the spindle assembly checkpoint. The spindle assembly checkpoint monitors proper attachment of all kinetochores to microtubules and tension between the kinetochores of sister chromatids to prevent premature anaphase entry. To this end, the activated spindle assembly checkpoint suppresses the E3 ubiquitin ligase activity of the anaphase-promoting complex (APC). In the continued presence of conditions that activate the spindle assembly checkpoint, cells eventually escape from mitosis by slippage. It has not been directly tested whether APC activation accompanies slippage. Using cells blocked in mitosis with the microtubule assembly inhibitor nocodazole, we show that mitotic APC substrates are degraded upon mitotic slippage. To confirm that APC is normally activated upon mitotic slippage we have found that knockdown of Cdc20 and Cdh1, two mitotic activators of APC, prevents the degradation of APC substrates during mitotic slippage. We provide the first direct demonstration that despite conditions that activate the spindle checkpoint, APC is indeed activated upon mitotic slippage of cells to interphase cells. Activation of the spindle checkpoint by microtubule targeting drugs used in chemotherapy may not indefinitely prevent APC activation. PMID:20436289

  3. Cross-Talk between AURKA and Plk1 in Mitotic Entry and Spindle Assembly

    PubMed Central

    Asteriti, Italia Anna; De Mattia, Fabiola; Guarguaglini, Giulia

    2015-01-01

    The Aurora kinase A (AURKA) is involved in different aspects of mitotic control, from mitotic entry to cytokinesis. Consistent with its pleiotropic roles, several AURKA interactors are able to modulate its activity, the best characterized being the microtubule-binding protein TPX2, the centrosomal protein Cep192, and Bora. Bora has been described as an essential cofactor of AURKA for phosphorylation-mediated activation of the mitotic kinase polo-like kinase 1 (Plk1) at the G2/M transition. A complex AURKA/Plk1 signaling axis is emerging, with multiple involved actors; recent data suggest that this control network is not restricted to mitotic entry only, but operates throughout mitosis. Here, we integrate available data from the literature to depict the complex interplay between AURKA and Plk1 in G2 and mitosis and how it contributes to their mitotic functions. We will particularly focus on how the activity of specifically localized AURKA/Plk1 pools is modulated in time and space by their reciprocal regulation to ensure the timely and coordinated unfolding of downstream mitotic events. PMID:26779436

  4. Dual function microtubule- and mitochondria-associated proteins mediate mitotic cell death

    PubMed Central

    Liu, Leyuan; Xie, Rui; Yang, Chaofeng; McKeehan, Wallace L.

    2011-01-01

    Background Survival and evolution of aneuploid cells after an asymmetric segregation of chromosomes at mitosis may be the common initiating event and underlying cause of the genetic diversity and adaptability of cancers. We hypothesize that mechanisms exist to detect impending aneuploidy and prevent it before completion of an aberrant mitosis. Methods The distribution of isoforms of C19ORF5, an interactive partner with mitochondria-associated LRPPRC and tumor suppressor RASSF1A, state of spindle microtubules and mitochondrial aggregation was analyzed in synchronized mitotic cells and cells stalled in mitosis after treatment with paclitaxel. Results C19ORF5 distributed broadly across the mitotic spindle and reversibly accumulated during reversible mitotic arrest. Prolonged stabilization of microtubules caused an accumulation of a C19ORF5 product with dual MAP and MtAP properties that caused irreversible aggregation of mitochondria and death of mitotic cells. Conclusion Dual function microtubule-associated (MAP) and mitochondria-associated (MtAP) proteins generated by prolonged mitotic arrest trigger mitochondrial-induced mitotic cell death. This is a potential mechanism to prevent minimal survivable aneuploidy resulting from an aberrant cell division and cancers in general at their earliest common origin. PMID:19759419

  5. Analogues to features and processes of a high-level radioactive waste repository proposed for Yucca Mountain, Nevada

    USGS Publications Warehouse

    Simmons, Ardyth M.; Stuckless, John S.; with a Foreword by Abraham Van Luik, U.S. Department of Energy

    2010-01-01

    Natural analogues are defined for this report as naturally occurring or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have taken place over time periods of decades to millennia and on spatial scales as much as tens of kilometers. Analogues provide an important temporal and spatial dimension that cannot be tested by laboratory or field-scale experiments. Analogues provide one of the multiple lines of evidence intended to increase confidence in the safe geologic disposal of high-level radioactive waste. Although the work in this report was completed specifically for Yucca Mountain, Nevada, as the proposed geologic repository for high-level radioactive waste under the U.S. Nuclear Waste Policy Act, the applicability of the science, analyses, and interpretations is not limited to a specific site. Natural and anthropogenic analogues have provided and can continue to provide value in understanding features and processes of importance across a wide variety of topics in addressing the challenges of geologic isolation of radioactive waste and also as a contribution to scientific investigations unrelated to waste disposal. Isolation of radioactive waste at a mined geologic repository would be through a combination of natural features and engineered barriers. In this report we examine analogues to many of the various components of the Yucca Mountain system, including the preservation of materials in unsaturated environments, flow of water through unsaturated volcanic tuff, seepage into repository drifts, repository drift stability, stability and alteration of waste forms and components of the engineered barrier system, and transport of radionuclides through unsaturated and saturated rock zones.

  6. Control of high oceanic features and subduction channel on earthquake ruptures along the Chile-Peru subduction zone

    NASA Astrophysics Data System (ADS)

    Contreras-Reyes, Eduardo; Carrizo, Daniel

    2011-05-01

    We discuss the earthquake rupture behavior along the Chile-Peru subduction zone in terms of the buoyancy of the subducting high oceanic features (HOF's), and the effect of the interplay between HOF and subduction channel thickness on the degree of interplate coupling. We show a strong relation between subduction of HOF's and earthquake rupture segments along the Chile-Peru margin, elucidating how these subducting features play a key role in seismic segmentation. Within this context, the extra increase of normal stress at the subduction interface is strongly controlled by the buoyancy of HOF's which is likely caused by crustal thickening and mantle serpentinization beneath hotspot ridges and fracture zones, respectively. Buoyancy of HOF's provide an increase in normal stress estimated to be as high as 10-50 MPa. This significant increase of normal stress will enhance seismic coupling across the subduction interface and hence will affect the seismicity. In particular, several large earthquakes (Mw ≥ 7.5) have occurred in regions characterized by subduction of HOF's including fracture zones (e.g., Nazca, Challenger and Mocha), hotspot ridges (e.g., Nazca, Iquique, and Juan Fernández) and the active Nazca-Antarctic spreading center. For instance, the giant 1960 earthquake (Mw = 9.5) is coincident with the linear projections of the Mocha Fracture Zone and the buoyant Chile Rise, while the active seismic gap of north Chile spatially correlates with the subduction of the Iquique Ridge. Further comparison of rupture characteristics of large underthrusting earthquakes and the locations of subducting features provide evidence that HOF's control earthquake rupture acting as both asperities and barriers. This dual behavior can be partially controlled by the subduction channel thickness. A thick subduction channel smooths the degree of coupling caused by the subducted HOF which allows lateral earthquake rupture propagation. This may explain why the 1960 rupture propagates through six major fracture zones, and ceased near the Mocha Fracture Zone in the north and at the Chile Rise in the south (regions characterized by a thin subduction channel). In addition, the thin subduction channel (north of the Juan Fernández Ridge) reflects a heterogeneous frictional behavior of the subduction interface which appears to be mainly controlled by the subduction of HOF's.

  7. Realizing one-dimensional quantum and high-frequency transport features in aligned single-walled carbon nanotube ropes

    NASA Astrophysics Data System (ADS)

    Ncube, Siphephile; Chimowa, George; Chiguvare, Zivayi; Bhattacharyya, Somnath

    2014-07-01

    The superiority of the electronic transport properties of single-walled carbon nanotube (SWNT) ropes over SWNT mats is verified from low temperature and frequency-dependent transport. The overall change of resistance versus in nanotube mats shows that 3D variable range hopping is the dominant conduction mechanism within the 2-300 K range. The magneto-resistance (MR) is found to be predominantly negative with a parabolic nature, which can also be described by the hopping model. Although the positive upturn of the MR at low temperatures establishes the contribution from quantum interference, the inherent quantum transport in individual tubes is suppressed at elevated temperatures. Therefore, to minimize multi-channel effects from inter-tube interactions and other defects, two-terminal devices were fabricated from aligned SWNT (extracted from a mat) for low temperature transport as well as high-frequency measurements. In contrast to the mat, the aligned ropes exhibit step-like features in the differential conductance within the 80-300 K temperature range. The effects of plasmon propagation, unique to one dimension, were identified in electronic transport as a non-universal power-law dependence of the differential conductance on temperature and source-drain voltage. The complex impedance showed high power transmission capabilities up to 65 GHz as well as oscillations in the frequency range up to 30 GHz. The measurements suggest that aligned SWNT ropes have a realistic potential for high-speed device applications.

  8. Uncovering immobilized trypsin digestion features from large-scale proteome data generated by high-resolution mass spectrometry

    PubMed Central

    Sun, Liangliang; Zhu, Guijie; Yan, Xiaojing; Mou, Si; Dovichi, Norman J.

    2014-01-01

    Immobilized trypsin produces very fast protein digestion, which is attractive for application to high throughput bottom-up proteomics. While there is a rich literature on the preparation of immobilized trypsin, there are very few studies that investigate its application to complex proteomic samples. In this work, we compared solution-phase trypsin with trypsin immobilized on magnetic microspheres for digestion of two complex proteomes, E. coli and the MCF7 cell line. The digests were separated by HPLC, and detected with a Q-Exactive mass spectrometer, which generated high resolution and high quality parent- and fragment-ion mass spectra. The data were analyzed using MaxQuant. We make several conclusions about the features of immobilized trypsin digestion of complex proteomes. First, both immobilized and solution-phase trypsin generate peptides that sample the same protein pool. Second, immobilized trypsin can digest complex proteomes two orders of magnitude faster than solution-phase trypsin while retaining similar numbers of protein identifications and proteome depth. Digestion using immobilized trypsin for 5-min produces a similar number of missed cleavages as solution-based trypsin digestion for 4-hr; digestion using immobilized trypsin for 20-min produces a similar number of missed cleavages as solution-based trypsin digestion for 12-hr. Third, immobilized trypsin produces quantitatively reproducible digestion of complex proteomes. Finally, there is small but measureable loss of peptide due to non-specific adsorption to the immobilization matrix. This adsorption generates a bias against detection of basic peptides. PMID:24636566

  9. Realizing one-dimensional quantum and high-frequency transport features in aligned single-walled carbon nanotube ropes

    SciTech Connect

    Ncube, Siphephile; Chimowa, George; Chiguvare, Zivayi; Bhattacharyya, Somnath

    2014-07-14

    The superiority of the electronic transport properties of single-walled carbon nanotube (SWNT) ropes over SWNT mats is verified from low temperature and frequency-dependent transport. The overall change of resistance versus in nanotube mats shows that 3D variable range hopping is the dominant conduction mechanism within the 2–300 K range. The magneto-resistance (MR) is found to be predominantly negative with a parabolic nature, which can also be described by the hopping model. Although the positive upturn of the MR at low temperatures establishes the contribution from quantum interference, the inherent quantum transport in individual tubes is suppressed at elevated temperatures. Therefore, to minimize multi-channel effects from inter-tube interactions and other defects, two-terminal devices were fabricated from aligned SWNT (extracted from a mat) for low temperature transport as well as high-frequency measurements. In contrast to the mat, the aligned ropes exhibit step-like features in the differential conductance within the 80–300 K temperature range. The effects of plasmon propagation, unique to one dimension, were identified in electronic transport as a non-universal power-law dependence of the differential conductance on temperature and source-drain voltage. The complex impedance showed high power transmission capabilities up to 65 GHz as well as oscillations in the frequency range up to 30 GHz. The measurements suggest that aligned SWNT ropes have a realistic potential for high-speed device applications.

  10. Breast cancer mitosis detection in histopathological images with spatial feature extraction

    NASA Astrophysics Data System (ADS)

    Albayrak, Abdülkadir; Bilgin, Gökhan

    2013-12-01

    In this work, cellular mitosis detection in histopathological images has been investigated. Mitosis detection is very expensive and time consuming process. Development of digital imaging in pathology has enabled reasonable and effective solution to this problem. Segmentation of digital images provides easier analysis of cell structures in histopathological data. To differentiate normal and mitotic cells in histopathological images, feature extraction step is very crucial step for the system accuracy. A mitotic cell has more distinctive textural dissimilarities than the other normal cells. Hence, it is important to incorporate spatial information in feature extraction or in post-processing steps. As a main part of this study, Haralick texture descriptor has been proposed with different spatial window sizes in RGB and La*b* color spaces. So, spatial dependencies of normal and mitotic cellular pixels can be evaluated within different pixel neighborhoods. Extracted features are compared with various sample sizes by Support Vector Machines using k-fold cross validation method. According to the represented results, it has been shown that separation accuracy on mitotic and non-mitotic cellular pixels gets better with the increasing size of spatial window.

  11. The impact of Highly Active Antiretroviral Therapy (HAART) on the clinical features of HIV - related oral lesions in Nigeria

    PubMed Central

    2010-01-01

    Background This study aimed to determine the therapeutic effects of highly active anti-retroviral therapy (HAART) on the clinical presentations of HIV related oral lesions (HIV-ROLs) in an adult Nigerian population. Methods A 5 month prospective study on HAART nave HIV positive adults recruited into the HAART program of an AIDS referral centre. HIV-ROLs were diagnosed clinically by the EEC Clearinghouse on oral problems related to HIV infection. Baseline clinical features of HIV-ROLs was documented by clinical photographs using SONY 5.2 M Cybershot digital camera. Post HAART monthly review was conducted using clinical photographs. Results A total of 142 patients were seen. Age range was 19 - 75 years. Mean age was 35.6 10.5 (SD). Eighty (56.3%) were females. Prevalence of HIV-ROLs was 43.7%. Oral candidiasis (22.4%) was the most prevalent HIV-ROL. 114 (83.2%) patients had clinical AIDS at presentation (CDC 1993). 89.4% were placed on Tenofovir/Emtricitabine +`Nevirapine, 9.9% on Tenofovir/Emtricitabine + Efavirenz. There was strong decline in the clinical features of oral candidiasis from a month of commencing HAART. Oral hairy leukoplakia was slow in responding to HAART. Parotid gland enlargement, melanotic hyperpigmentation and Kaposi's sarcoma were more persistent and had slower response to HAART. There was no clinical change noticed in linear gingival erythema. Conclusion HAART has different clinical effects on HIV related oral lesions depending on the size, duration of treatment and etiology of the lesions. HIV-ROLs of fungal origin have the fastest response to HAART. These lesions alongside immunologic parameters can be used as indicators of success or failure of antiretroviral therapy. PMID:20579347

  12. The Silicon and Calcium High-velocity Features in Type Ia Supernovae from Early to Maximum Phases

    NASA Astrophysics Data System (ADS)

    Zhao, Xulin; Wang, Xiaofeng; Maeda, Keiichi; Sai, Hanna; Zhang, Tianmeng; Zhang, Jujia; Huang, Fang; Rui, Liming; Zhou, Qi; Mo, Jun

    2015-09-01

    The high-velocity features (HVFs) in optical spectra of type Ia supernovae (SNe Ia) are examined with a large sample including very early-time spectra (e.g., t < -7 days). Multiple Gaussian fits are applied to examine the HVFs and their evolutions, using constraints on expansion velocities for the same species (i.e., Si ii 5972 and Si ii 6355). We find that strong HVFs tend to appear in SNe Ia with smaller decline rates (e.g., ?m15(B) ? 1.4 {mag}), clarifying that the finding by Childress et al. for the Ca-HVFs in near-maximum-light spectra applies both to the Si-HVFs and Ca-HVFs in the earlier phase. The Si-HVFs seem to be more common in rapidly expanding SNe Ia, which is different from the earlier result that Ca-HVFs are associated with SNe Ia that have slower Si ii 6355 velocities at maximum light (i.e., VSimax). Moreover, SNe Ia with both stronger HVFs at early phases and larger VSimax are found to have noticeably redder B-V colors and to occur preferentially in the inner regions of their host galaxies, while those with stronger HVFs but smaller VSimax show opposite tendencies, suggesting that these two subclasses have different explosion environments and their HVFs may have different origins. We further examine the relationships between the absorption features of Si ii 6355 and Ca ii IR lines, and find that their photospheric components are well correlated in velocity and strength but that the corresponding HVFs show larger scatter. These results cannot be explained with ionization and/or thermal processes alone, and different mechanisms are required for the creation of HVF-forming regions in SNe Ia.

  13. Structural and Process Features in Three Types of Child Care for Children from High and Low Income Families

    PubMed Central

    Dowsett, Chantelle J.; Huston, Aletha C.; Imes, Amy E.

    2009-01-01

    We use observations from the NICHD Study of Early Child Care and Youth Development (SECCYD) to compare structural and process characteristics of child care centers, family child care homes (nonrelative care in a home setting) and care by relatives for 2, 3- and 4 -year-old children. Type of care differences in structural and caregiver characteristics were consistent across ages: centers had higher child-to-adult ratios and bigger groups; centers had caregivers with better education, more training in early childhood, and less traditional beliefs about child rearing. Children in centers experienced more cognitive stimulation, less frequent language interactions with adults, less frequent negative interactions with adults, and less television viewing than did those in other types of care. In centers and family child care homes compared to relative settings, children engaged in more positive and negative interactions with peers and spent more time in transition and unoccupied. Curvilinear associations were found between structural features of care and family income, particularly for caregiver education and training. In contrast, process measures of caregiving rose monotonically with family income. Children from high-income families experienced more sensitive care, more cognitive stimulation, and fewer negative interactions with adults than did those from low-income families. We interpret the findings by linking the structural features and caregiver training to the cognitive and social processes observed in different types of care. Future research designed to understand the influences of child care on children's behavior might benefit from using this more nuanced description of child care experiences. PMID:19609366

  14. PERCUTANEOUS BIOPSY OF PRIMARY TUMOR IN METASTATIC RENAL CELL CARCINOMA TO PREDICT HIGH RISK PATHOLOGIC FEATURES: COMPARISON WITH NEPHRECTOMY ASSESSMENT

    PubMed Central

    Abel, E. Jason; Culp, Stephen H.; Matin, Surena; Tamboli, Pheroze; Wallace, Michael J.; Jonasch, Eric; Tannir, Nizar M.; Wood, Christopher G.

    2016-01-01

    PURPOSE As treatment options evolve in metastatic renal cell carcinoma (mRCC), there is need for predictive information to help guide therapy. The purpose of this study was to assess accuracy of percutaneous primary tumor biopsy in mRCC by comparing biopsy findings to final nephrectomy pathology in patients undergoing cytoreductive nephrectomy (CN). MATERIALS AND METHODS Using an institutional database, we reviewed records of patients who underwent percutaneous primary tumor biopsy prior to CN. For patients who underwent biopsy at an outside institution, pathology was re-reviewed at our institution. Differences in accuracy based on biopsy technique, imaging modality, and biopsy time period were determined using chi-square analysis. RESULTS We identified 166 patients who underwent percutaneous biopsy of the primary tumor prior to CN between 1991 and 2007 and had data available for review. Median pathologic tumor size was 9.1 cm (range 3–32). Median time from biopsy to surgery was 46 days (range 6–717). Of 104 patients whose biopsy was assigned a Fuhrman nuclear grade, 33 (31.7%) had the same grade in the nephrectomy specimen or 74 of 109 (67.9%) when only high or low grade was considered. Grade change by more than 2 points was seen in 18 of 104 (17.3%) patients. Sarcomatoid features were present in 34 of 166 (20.5%) nephrectomy specimens, however only 4 (11.8%) were identified pre-operatively. CONCLUSIONS In patients with mRCC, percutaneous renal biopsy has poor accuracy for assessment of Fuhrman nuclear grade or sarcomatoid features. Physicians should use caution when using biopsy data to guide therapy. PMID:20850148

  15. Design and operating features of the high-level waste vitrification system for the West Valley demonstration project

    SciTech Connect

    Siemens, D.H.; Beary, M.M.; Barnes, S.M.; Berger, D.N.; Brouns, R.A.; Chapman, C.C.; Jones, R.M.; Peters, R.D.; Peterson, M.E.

    1986-03-01

    A liquid-fed joule-heated ceramic melter system is the reference process for immobilization of the high-level liquid waste in the US and several foreign countries. This system has been under development for over ten years at Pacific Northwest Laboratory and other national laboratories operated for the US Department of Energy. Pacific Northwest Laboratory contributed to this research through its Nuclear Waste Treatment Program and used applicable data to design and test melters and related systems using remote handling of simulated radioactive wastes. This report describes the equipment designed in support of the high-level waste vitrification program at West Valley, New York. Pacific Northwest Laboratory worked closely with West Valley Nuclear Services Company to design a liquid-fed ceramic melter, a liquid waste preparation and feed tank and pump, an off-gas treatment scrubber, and an enclosed turntable for positioning the waste canisters. Details of these designs are presented including the rationale for the design features and the alternatives considered.

  16. Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 increase in UV irradiated cells and during meiosis but not during the mitotic cell cycle.

    PubMed

    Jones, J S; Prakash, L

    1991-02-25

    We have examined the transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 in UV irradiated cells, in the