Sample records for features high mitotic

  1. 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

  2. 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

  3. The Drosophila salivary gland chromocenter contains highly polytenized subdomains of mitotic heterochromatin.

    PubMed

    Zhang, P; Spradling, A C

    1995-02-01

    Peri-centromeric regions of Drosophila melanogaster chromosomes appear heterochromatic in mitotic cells and become greatly underrepresented in giant polytene chromosomes, where they aggregate into a central mass called the chromocenter. We used P elements inserted at sites dispersed throughout much of the mitotic heterochromatin to analyze the fate of 31 individual sites during polytenization. Analysis of DNA sequences flanking many of these elements revealed that middle repetitive or unique sequence DNAs frequently are interspersed with satellite DNAs in mitotic heterochromatin. All nine Y chromosome sites tested were underrepresented > 20-fold on Southern blots of polytene DNA and were rarely or never detected by in situ hybridization to salivary gland chromosomes. In contrast, nine tested insertions in autosomal centromeric heterochromatin were represented fully in salivary gland DNA, despite the fact that at least six were located proximal to known blocks of satellite DNA. The inserted sequences formed diverse, site-specific morphologies in the chromocenter of salivary gland chromosomes, suggesting that domains dispersed at multiple sites in the centromeric heterochromatin of mitotic chromosomes contribute to polytene beta-heterochromatin. We suggest that regions containing heterochromatic genes are organized into dispersed chromatin configurations that are important for their function in vivo. PMID:7713423

  4. Genome-Wide High-Resolution Mapping of UV-Induced Mitotic Recombination Events in Saccharomyces cerevisiae

    PubMed Central

    Yin, Yi; Petes, Thomas D.

    2013-01-01

    In the yeast Saccharomyces cerevisiae and most other eukaryotes, mitotic recombination is important for the repair of double-stranded DNA breaks (DSBs). Mitotic recombination between homologous chromosomes can result in loss of heterozygosity (LOH). In this study, LOH events induced by ultraviolet (UV) light are mapped throughout the genome to a resolution of about 1 kb using single-nucleotide polymorphism (SNP) microarrays. UV doses that have little effect on the viability of diploid cells stimulate crossovers more than 1000-fold in wild-type cells. In addition, UV stimulates recombination in G1-synchronized cells about 10-fold more efficiently than in G2-synchronized cells. Importantly, at high doses of UV, most conversion events reflect the repair of two sister chromatids that are broken at approximately the same position whereas at low doses, most conversion events reflect the repair of a single broken chromatid. Genome-wide mapping of about 380 unselected crossovers, break-induced replication (BIR) events, and gene conversions shows that UV-induced recombination events occur throughout the genome without pronounced hotspots, although the ribosomal RNA gene cluster has a significantly lower frequency of crossovers. PMID:24204306

  5. Temporal models for mitotic phase labelling.

    PubMed

    El-Labban, A; Zisserman, A; Toyoda, Y; Bird, A W; Hyman, A

    2014-10-01

    With the widespread use of time-lapse data to understand cellular function, there is a need for tools which facilitate high-throughput analysis of data. Fluorescence microscopy of genetically engineered cell lines in culture can be used to visualise the progression of these cells through the cell cycle, including distinctly identifiable sequential stages of cell division (mitotic phases). We present a system for automated segmentation and mitotic phase labelling using temporal models. This work takes the novel approach of using temporal features evaluated over the whole of the mitotic phases rather than over single frames, thereby capturing the distinctive behaviour over the phases. We compare and contrast three different temporal models: Dynamic Time Warping, Hidden Markov Models, and Semi Markov Models. A new loss function is proposed for the Semi Markov model to make it more robust to inconsistencies in data annotation near transition boundaries. The models are tested under two different experimental conditions to explore robustness to changes in biological conditions. PMID:24972376

  6. Condensin: Architect of mitotic chromosomes

    Microsoft Academic Search

    Damien F. Hudson; Kathryn M. Marshall; William C. Earnshaw

    2009-01-01

    Condensin is a highly conserved pentameric complex consisting of two structural maintenance of chromosome (SMC) ATPase subunits\\u000a and three auxiliary components. While initially regarded as a key driver of mitotic chromosome condensation, condensin is\\u000a increasingly viewed as having a more subtle influence on chromosome architecture. The two condensin complexes are required\\u000a to direct the correct folding and organization of chromosomes

  7. 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

  8. Tissue-Specific Mitotic Bookmarking by Hematopoietic Transcription

    E-print Network

    Hardison, Ross C.

    Tissue-Specific Mitotic Bookmarking by Hematopoietic Transcription Factor GATA1 Stephan Kadauke,1 lineage fidelity. We investigated whether transcription factor GATA1 plays a role in transmitting-cell imaging revealed that a fraction of GATA1 is retained focally within mitotic chromatin. ChIP-seq of highly

  9. A Framework for Image-Based Classification of Mitotic Cells in Asynchronous Populations

    PubMed Central

    Slattery, Scott D.; Newberg, Justin Y.; Szafran, Adam T.; Hall, Rebecca M.; Brinkley, Bill R.

    2012-01-01

    Abstract High content screening (HCS) has emerged an important tool for drug discovery because it combines rich readouts of cellular responses in a single experiment. Inclusion of cell cycle analysis into HCS is essential to identify clinically suitable anticancer drugs that disrupt the aberrant mitotic activity of cells. One challenge for integration of cell cycle analysis into HCS is that cells must be chemically synchronized to specific phases, adding experimental complexity to high content screens. To address this issue, we have developed a rules-based method that utilizes mitotic phosphoprotein monoclonal 2 (MPM-2) marker and works consistently in different experimental conditions and in asynchronous populations. Further, the performance of the rules-based method is comparable to established machine learning approaches for classifying cell cycle data, indicating the robustness of the features we use in the framework. As such, we suggest the use of MPM-2 analysis and its associated expressive features for integration into HCS approaches. PMID:22084958

  10. Mitotically active cellular fibroma of the ovary: a case report and a review of the literature.

    PubMed

    Wu, H; Xie, J; Huang, W; Wu, J

    2014-01-01

    Mitotically active cellular fibroma (MACF) is characterized by increased cellularity, mitotic activity, and less frequently, nuclear atypia, which comprises 10% of ovarian fibromatous tumors. The authors report the case of a 76-year-old woman who presented at the present hospital with a two-month pelvic mass. B ultrasound disclosed a 75 x 52 x 41 mm mass in the right accessories. A hysterectomy and bilateral salpingo-oophorectomy was performed. Histologically, the tumor was composed of a densely cellular proliferation of fibrolastic-like cells with bland nuclear features and arranged in a fascicular pattern. There were more than four mitotic figures per ten high-power fields (HPFs). The histological diagnosis for the mass of the right ovary was MACF. MACF should be distinguished from ovarian fibrosarcoma. MACF is a recent histopathologic entity. Despite the high count of mitotic figures, the clinical course of the tumor is typically uneventful. Long-term clinical follow-up is recommended. PMID:24654469

  11. Yeast Nap1-binding protein Nbp2p is required for mitotic growth at high temperatures and for cell wall integrity.

    PubMed Central

    Ohkuni, Kentaro; Okuda, Asuko; Kikuchi, Akihiko

    2003-01-01

    Nbp2p is a Nap1-binding protein in Saccharomyces cerevisiae identified by its interaction with Nap1 by a two-hybrid system. NBP2 encodes a novel protein consisting of 236 amino acids with a Src homology 3 (SH3) domain. We showed that NBP2 functions to promote mitotic cell growth at high temperatures and cell wall integrity. Loss of Nbp2 results in cell death at high temperatures and in sensitivity to calcofluor white. Cell death at high temperature is thought not to be due to a weakened cell wall. Additionally, we have isolated several type-2C serine threonine protein phosphatases (PTCs) as multicopy suppressors and MAP kinase-kinase (MAPKK), related to the yeast PKC MAPK pathway, as deletion suppressors of the nbp2Delta mutant. Screening for deletion suppressors is a new genetic approach to identify and characterize additional proteins in the Nbp2-dependent pathway. Genetic analyses suggested that Ptc1, which interacts with Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is indispensable when Nbp2 is deleted at high temperature. PMID:14573466

  12. Cell biology of mitotic recombination.

    PubMed

    Lisby, Michael; Rothstein, Rodney

    2015-03-01

    Homologous recombination provides high-fidelity DNA repair throughout all domains of life. Live cell fluorescence microscopy offers the opportunity to image individual recombination events in real time providing insight into the in vivo biochemistry of the involved proteins and DNA molecules as well as the cellular organization of the process of homologous recombination. Herein we review the cell biological aspects of mitotic homologous recombination with a focus on Saccharomyces cerevisiae and mammalian cells, but will also draw on findings from other experimental systems. Key topics of this review include the stoichiometry and dynamics of recombination complexes in vivo, the choreography of assembly and disassembly of recombination proteins at sites of DNA damage, the mobilization of damaged DNA during homology search, and the functional compartmentalization of the nucleus with respect to capacity of homologous recombination. PMID:25731763

  13. Mitotic Illegitimate Recombination Is a Mechanism for Novel Changes in High-Molecular-Weight Glutenin Subunits in Wheat-Rye Hybrids

    PubMed Central

    Yuan, Zhongwei; Liu, Dengcai; Zhang, Lianquan; Zhang, Li; Chen, Wenjie; Yan, Zehong; Zheng, Youliang; Zhang, Huaigang; Yen, Yang

    2011-01-01

    Wide hybrids can have novel traits or changed expression of a quantitative trait that their parents do not have. These phenomena have long been noticed, yet the mechanisms are poorly understood. High-molecular-weight glutenin subunits (HMW-GS) are seed storage proteins encoded by Glu-1 genes that only express in endosperm in wheat and its related species. Novel HMW-GS compositions have been observed in their hybrids. This research elucidated the molecular mechanisms by investigating the causative factors of novel HMW-GS changes in wheat-rye hybrids. HMW-GS compositions in the endosperm and their coding sequences in the leaves of F1 and F2 hybrids between wheat landrace Shinchunaga and rye landrace Qinling were investigated. Missing and/or additional novel HMW-GSs were observed in the endosperm of 0.5% of the 2078 F1 and 22% of 36 F2 hybrid seeds. The wildtype Glu-1Ax null allele was found to have 42 types of short repeat sequences of 3-60 bp long that appeared 2 to 100 times. It also has an in-frame stop codon in the central repetitive region. Analyzing cloned allele sequences of HMW-GS coding gene Glu-1 revealed that deletions involving the in-frame stop codon had happened, resulting in novel ?1.8-kb Glu-1Ax alleles in some F1 and F2 plants. The cloned mutant Glu-1Ax alleles were expressed in Escherichia coli, and the HMW-GSs produced matched the novel HMW-GSs found in the hybrids. The differential changes between the endosperm and the plant of the same hybrids and the data of E. coli expression of the cloned deletion alleles both suggested that mitotic illegitimate recombination between two copies of a short repeat sequence had resulted in the deletions and thus the changed HMW-GS compositions. Our experiments have provided the first direct evidence to show that mitotic illegitimate recombination is a mechanism that produces novel phenotypes in wide hybrids. PMID:21887262

  14. Caffeic acid phenethyl ester, a major component of propolis, suppresses high fat diet-induced obesity through inhibiting adipogenesis at the mitotic clonal expansion stage.

    PubMed

    Shin, Seung Ho; Seo, Sang Gwon; Min, Soyun; Yang, Hee; Lee, Eunjung; Son, Joe Eun; Kwon, Jung Yeon; Yue, Shuhua; Chung, Min-Yu; Kim, Kee-Hong; Cheng, Ji-Xin; Lee, Hyong Joo; Lee, Ki Won

    2014-05-14

    In the present study, we aimed to investigate the antiobesity effect of CAPE in vivo, and the mechanism by which CAPE regulates body weight in vitro. To confirm the antiobesity effect of CAPE in vivo, mice were fed with a high fat diet (HFD) with different concentrations of CAPE for 5 weeks. CAPE significantly reduced body weight gain and epididymal fat mass in obese mice fed a HFD. In accordance with in vivo results, Oil red O staining results showed that CAPE significantly suppressed MDI-induced adipogenesis of 3T3-L1 preadipocytes. FACS analysis results showed that CAPE delayed MDI-stimulated cell cycle progression, thereby contributing to inhibit mitotic clonal expansion (MCE), which is a prerequisite step for adipogenesis. Also, CAPE regulated the expression of cyclin D1 and the phosphorylation of ERK and Akt, which are upstream of cyclin D1. These results suggest that CAPE exerts an antiobesity effect in vivo, presumably through inhibiting adipogenesis at an early stage of adipogenesis. PMID:24611533

  15. The Conserved N-Terminal Region of the Mitotic Checkpoint Protein BUBR1: A Putative TPR Motif of High Surface Activity

    PubMed Central

    Bolanos-Garcia, V. M.; Beaufils, S.; Renault, A.; Grossmann, J. G.; Brewerton, S.; Lee, M.; Venkitaraman, A.; Blundell, T. L.

    2005-01-01

    BUBR1, a key component of the mitotic spindle checkpoint, is a multidomain protein kinase that is activated in response to kinetochore tension. Although BUB1 and BUBR1 play an important role in cell division, very little is known about their structural characteristics. We show that the conserved N-terminal region of BUBR1, comprising residues 1–204, is a globular domain of high ?-helical content (?60%), stable in the pH range 4–9 and probably organized as a tetratricopeptide motif repeat (TPR), most closely resembling residues 16–181 of protein phosphatase 5. Because the latter presents a continuous amphipathic groove and is regulated by binding certain fatty acids, we compared the properties of BUBR1(1–204) and TPR-PP5(16–181) at air/water interfaces and found that both proteins exhibited a similar surface activity and formed stable, rigid monolayers. The deletion of a region that probably comprises several ?-helices of BUBR1 indicates that long-range interactions are essential for the stability of the N-terminal domain. The presence of the putative TPR motif strongly suggests that the N-terminal domain of BUBR1 is involved in direct protein-protein interactions and/or protein-lipid interactions. PMID:16040755

  16. 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

  17. 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.

  18. Chromosome loops arising from intrachromosomal tethering of telomeres occur at high frequency in G1 (non-cycling) mitotic cells: Implications for telomere capture

    PubMed Central

    Daniel, Art; St Heaps, Luke

    2004-01-01

    Background To investigate potential mechanisms for telomere capture the spatial arrangement of telomeres and chromosomes was examined in G1 (non-cycling) mitotic cells with diploid or triploid genomes. This was examined firstly by directly labelling the respective short arm (p) and long arm subtelomeres (q) with different fluorophores and probing cell preparations using a number of subtelomere probe pairs, those for chromosomes 1, 3, 4, 5, 6, 7, 9, 10, 12, 17, 18, and 20. In addition some interstitial probes (CEN15, PML and SNRPN on chromosome 15) and whole chromosome paint probes (e.g. WCP12) were jointly hybridised to investigate the co-localization of interphase chromosome domains and tethered subtelomeres. Cells were prepared by omitting exposure to colcemid and hypotonic treatments. Results In these cells a specific interphase chromosome topology was detected. It was shown that the p and q telomeres of the each chromosome associate frequently (80% pairing) in an intrachromosomal manner, i.e. looped chromosomes with homologues usually widely spaced within the nucleus. This p-q tethering of the telomeres from the one chromosome was observed with large (chromosomes 3, 4, 5), medium sized (6, 7, 9, 10, 12), or small chromosomes (17, 18, 20). When triploid nuclei were probed there were three tetherings of p-q subtelomere signals representing the three widely separated looped chromosome homologues. The separate subtelomere pairings were shown to coincide with separate chromosome domains as defined by the WCP and interstitial probes. The 20% of apparently unpaired subtelomeric signals in diploid nuclei were partially documented to be pairings with the telomeres of other chromosomes. Conclusions A topology for telomeres was detected where looped chromosome homologues were present at G1 interphase. These homologues were spatially arranged with respect to one-another independently of other chromosomes, i.e. there was no chromosome order on different sides of the cell nuclei and no segregation into haploid sets was detected. The normal function of this high frequency of intrachromosomal loops is unknown but a potential role is likely in the genesis of telomere captures whether of the intrachromosomal type or between non-homologues. This intrachromosomal tethering of telomeres cannot be related to telomeric or subtelomeric sequences since these are shared in varying degree with other chromosomes. In our view, these intrachromosomal telomeric tetherings with the resulting looped chromosomes arranged in a regular topology must be important to normal cell function since non-cycling cells in G1 are far from quiescent, are in fact metabolically active, and these cells represent the majority status since only a small proportion of cells are normally dividing. PMID:15453908

  19. 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. 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).

  20. Autoreducibility, Mitoticity, and Immunity Christian Glaer

    E-print Network

    Selman, Alan

    Autoreducibility, Mitoticity, and Immunity Christian Glaßer , Mitsunori Ogihara , A. Pavan , Alan L-mitotic. · If there is a tally language in NP coNP - P, then, for every > 0, NP-complete sets are not 2n(1+ ) -immune primarily on autoreducibility, mitoticity, and immunity. Trakhtenbrot [Tra70] introduced the notion

  1. 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

  2. EGF Induced Centrosome Separation Promotes Mitotic Progression and Cell Survival

    PubMed Central

    Mardin, Balca R.; Isokane, Mayumi; Cosenza, Marco R.; Krämer, Alwin; Ellenberg, Jan; Fry, Andrew M.; Schiebel, Elmar

    2014-01-01

    Summary Timely and accurate assembly of the mitotic spindle is critical for the faithful segregation of chromosomes and centrosome separation is a key step in this process. The timing of centrosome separation varies dramatically between cell types; however, the mechanisms responsible for these differences and its significance are unclear. Here, we show that activation of epidermal growth factor receptor (EGFR) signaling determines the timing of centrosome separation. Premature separation of centrosomes decreases the requirement for the major mitotic kinesin Eg5 for spindle assembly, accelerates mitosis and decreases the rate of chromosome missegregation. Importantly, EGF stimulation impacts upon centrosome separation and mitotic progression to different degrees in different cell lines. Cells with high EGFR levels fail to arrest in mitosis upon Eg5 inhibition. This has important implications for cancer therapy since cells with high centrosomal response to EGF are more susceptible to combinatorial inhibition of EGFR and Eg5. PMID:23643362

  3. Inhibition of histone deacetylase activity increases chromosomal instability by the aberrant regulation of mitotic checkpoint activation

    Microsoft Academic Search

    Hyun-Jin Shin; Kwan-Hyuck Baek; Ae-Hwa Jeon; So-Jung Kim; Kyung-Lib Jang; Young-Chul Sung; Chang-Min Kim; Chang-Woo Lee

    2003-01-01

    Histone modification through acetylation and deacetylation is a key process in transcription, DNA replication, and chromosome segregation. During mitosis, histones are highly acetylated and chromatin is condensed. Here, we investigate the mechanistic involvement of histone deacetylase (HDAC) activity in the regulation of mitotic checkpoint activation. Inhibition of HDAC activity was found to cause the improper kinetochore localization of the mitotic

  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. High-resolution Urban Image Classification Using Extended Features

    SciTech Connect

    Vatsavai, Raju [ORNL] [ORNL

    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.

  6. Feature selection in high dimensional regression problems for genomics

    E-print Network

    Paris-Sud XI, Université de

    Feature selection in high dimensional regression problems for genomics Julie Hamon1,2,3 , Clarisse, France julien.jacques@lifl.fr Abstract. In the context of genomic selection in animal breeding and "closed to real" datasets. Keywords: Feature selection, combinatorial optimization, regression, genomic. 1

  7. Analysis of high-level features for vocal emotion recognition

    Microsoft Academic Search

    Hicham Atassi; Anna Esposito; Zdenek Smekal

    2011-01-01

    The paper deals with the vocal emotion recognition which is a very important task for several applications in the field of human-machine interaction. There is a plenty of algorithms proposed up to date for this purpose that exploit different types of features and classifiers. Our previous work showed that high-level features perform very well in terms of emotion classification from

  8. Kinetochore capture and bi-orientation on the mitotic spindle

    Microsoft Academic Search

    Michael J. R. Stark; Kozo Tanaka; Tomoyuki U. Tanaka

    2005-01-01

    Kinetochores are large protein complexes that are formed on chromosome regions known as centromeres. For high-fidelity chromosome segregation, kinetochores must be correctly captured on the mitotic spindle before anaphase onset. During prometaphase, kinetochores are initially captured by a single microtubule that extends from a spindle pole and are then transported poleward along the microtubule. Subsequently, microtubules that extend from the

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

    SciTech Connect

    Cheriyadat, Anil M [ORNL

    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.

  10. 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

  11. 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.

  12. ATM controls proper mitotic spindle structure

    PubMed Central

    Palazzo, Luca; Della Monica, Rosa; Visconti, Roberta; Costanzo, Vincenzo; Grieco, Domenico

    2014-01-01

    The recessive ataxia-telangiectasia (A-T) syndrome is characterized by cerebellar degeneration, immunodeficiency, cancer susceptibility, premature aging, and insulin-resistant diabetes and is caused by loss of function of the ATM kinase, a member of the phosphoinositide 3-kinase–like protein kinases (PIKKs) family. ATM plays a crucial role in the DNA damage response (DDR); however, the complexity of A-T features suggests that ATM may regulate other cellular functions. Here we show that ATM affects proper bipolar mitotic spindle structure independently of DNA damage. In addition, we find that in mitosis ATM forms a complex with the poly(ADP)ribose (PAR) polymerase Tankyrase (TNKS) 1, the spindle pole protein NuMA1, and breast cancer susceptibility protein BRCA1, another crucial DDR player. Our evidence indicates that the complex is required for efficient poly(ADP)ribosylation of NuMA1. We find further that a mutant NuMA1 version, non-phosphorylatable at potential ATM-dependent phosphorylation sites, is poorly PARylated and induces loss of spindle bipolarity. Our findings may help to explain crucial A-T features and provide further mechanistic rationale for TNKS inhibition in cancer therapy. PMID:24553124

  13. The significance of mitotic rate: a retrospective study of 127 thyroid carcinomas.

    PubMed

    Lee, T K; Myers, R T; Marshall, R B; Bond, M G; Kardon, B

    1985-10-01

    The association between mitotic rate and biologic behavior was studied in 127 cases of thyroid cancer. Based on the observation of 12,700 high-power fields (HPF), the mitotic rate varied from 0 to 316 (33.3 +/- 4.9) mitoses/100 HPF. Mitotic rate differed among the four types of thyroid cancers and correlated inversely with the differentiation of the tumors, being highest (156.8 +/- 32.9) in the undifferentiated tumors and lowest (17.3 +/- 2.4) in the papillary tumors. By analysis of variance (AOVA), the relations between mitotic rate and the sex or age of the patient, maximal diameter of the tumor, and vascular or capsular invasion were assessed, but significant relations were not found (r2 = 44.2 per cent). Follow-up observation, possible in 74 patients, showed mitotic rate to be significantly related to the survival period (Student's t-test; P values ranging from 0.02 to 0.05). The patients who were alive five and ten years after surgery had had lower mitotic rates than those who had died during the same follow-up period. The correlation of low mitotic rate with a high degree of differentiation and low potential for invasion might, in part, explain the better surgical cure rates for papillary thyroid carcinoma than for other types of thyroid cancers. PMID:4043953

  14. 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.

  15. 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

  16. Object Classification and Detection in High Dimensional Feature Space

    E-print Network

    Bey, Isabelle

    : he is always there when you need him, ready to discuss new ideas, he has a deep knowledge not only and the appearance variations of object classes. This thesis improves upon several classical machine learning algorithms, enabling large computational gains in high dimensional feature space. A common trend in machine

  17. Real-Time Feature Extraction for High Speed Networks

    Microsoft Academic Search

    David Nguyen; Gokhan Memik; Seda Ogrenci Memik; Alok N. Choudhary

    2005-01-01

    With the onset of Gigabit networks, current generation networking components will soon be insufficient for numerous reasons: most notably because existing methods cannot support high performance demands. Feature extraction (or flow monitoring), an essential component in anomaly detection, summarizes network behavior from a packet stream. This information is fed into intrusion detection methods such as association rule mining, outlier analysis,

  18. NudC deacetylation regulates mitotic progression.

    PubMed

    Chuang, Carol; Pan, Jing; Hawke, David H; Lin, Sue-Hwa; Yu-Lee, Li-yuan

    2013-01-01

    Mitosis is largely driven by posttranslational modifications of proteins. Recent studies suggest that protein acetylation is prevalent in mitosis, but how protein acetylation/deacetylation regulates mitotic progression remains unclear. Nuclear distribution protein C (NudC), a conserved protein that regulates cell division, was previously shown to be acetylated. We found that NudC acetylation was decreased during mitosis. Using mass spectrometry analysis, we identified K39 to be an acetylation site on NudC. Reconstitution of NudC-deficient cells with wild-type or K39R acetylation-defective NudC rescued mitotic phenotypes, including chromosome misalignment, chromosome missegregation, and reduced spindle width, observed after NudC protein knockdown. In contrast, the K39Q acetylation-mimetic NudC was unable to rescue these mitotic phenotypes, suggesting that NudC deacetylation is important for mitotic progression. To examine proteins that may play a role in NudC deacetylation during mitosis, we found that NudC co-localizes on the mitotic spindle with the histone deacetylase HDAC3, an HDAC shown to regulate mitotic spindle stability. Further, NudC co-immunoprecipitates with HDAC3 and loss of function of HDAC3 either by protein knockdown or inhibition with a small molecule inhibitor increased NudC acetylation. These observations suggest that HDAC3 may be involved in NudC deacetylation during mitosis. Cells with NudC or HDAC3 knockdown exhibited overlapping mitotic abnormalities, including chromosomes arranged in a "dome-like" configuration surrounding a collapsed mitotic spindle. Our studies suggest that NudC acetylation/deacetylation regulates mitotic progression and NudC deacetylation, likely through HDAC3, is critical for spindle function and chromosome congression. PMID:24069238

  19. Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase.

    PubMed

    Nagai, Tomoaki; Ikeda, Masanori; Chiba, Shuhei; Kanno, Shin-Ichiro; Mizuno, Kensaku

    2013-10-01

    The structure and function of microtubules (MTs) are regulated by post-translational modifications of tubulin subunits, such as acetylation of the Lys40 residue of ?-tubulin. Regulation of the organization and dynamics of MTs is essential for the precise formation of the mitotic spindle. Spindle MTs are highly acetylated, but the mechanism regulating this acetylation is largely unknown. Furry (Fry) is an evolutionarily conserved protein that binds to MTs and colocalizes with acetylated MTs in the mitotic spindle. In this study, we examined the role of Fry in the acetylation of MTs in the mitotic spindle. Depletion of Fry significantly reduced the level of MT acetylation in the mitotic spindle. Expression of the N-terminal fragment of Fry induced hyperacetylation of MTs in both mitotic and interphase cells. These results indicate that Fry promotes MT acetylation in the mitotic spindle. We also found that Fry binds to the tubulin deacetylase SIRT2, preferentially in mitotic cells. Cell-free experiments revealed that the N-terminal region of Fry is the domain responsible for binding to and inhibiting the tubulin-deacetylase activity of SIRT2. AGK2, a specific inhibitor of SIRT2, increased the level of MT acetylation in the mitotic spindle, indicating that SIRT2 is involved in the deacetylation of spindle MTs. Furthermore, AGK2 reversed the decrease in MT acetylation induced by Fry depletion. In summary, these results suggest that Fry plays a crucial role in promoting the level of MT acetylation in the mitotic spindle by inhibiting the tubulin-deacetylase activity of SIRT2. PMID:23886946

  20. 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.

  1. Mitotic Waves in Laticifers of Euphorbia marginata.

    PubMed

    Mahlberg, P; Sabharwal, P

    1966-04-22

    A successive pattern of nuclear divisions that result in mitotic waves has been observed within the coenocytic nonarticulated laticifers of embryos of Euphorbia marginata Pursh. These waves originate independently in the cotyledonary or hypocotyl portion of the laticifer and exhibit uni-or bidirectional movement at variable velocities. Individual nuclei or groups of neighoring nuclei in a laticifer were observed in a sequence of mitotic stages ranging from prophase to telophase; division activity varied with individual laticifers in an embryo. Two mitotic patterns were apparent in the embryo: a random pattern associated with various cells in the meristematic area, and a successive pattern restricted to the laticifer. A substance, synthesized by and restricted to the laticifer, may be associated with this mitotic pattern. PMID:17815080

  2. Multifaceted folding in a foldamer featuring highly cooperative folds.

    PubMed

    Ramesh, Veera V E; Priya, Gowri; Kotmale, Amol S; Gonnade, Rajesh G; Rajamohanan, Pattuparambil R; Sanjayan, Gangadhar J

    2012-11-25

    Herein, we report on the folding pattern observed in a synthetic peptide featuring two highly mutually dependent, yet strikingly dissimilar, closed networks of hydrogen-bonded rings that work in a cumulative fashion to stabilize the entire folded architecture of the peptide. Structural studies unequivocally suggest that disruption of any one of these mutually-dependent hydrogen-bonded networks is deleterious to the stability of the fully folded conformation of the peptide. PMID:23051854

  3. The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

    PubMed Central

    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

  4. Binding of the vesicle docking protein p115 to Golgi membranes is inhibited under mitotic conditions.

    PubMed

    Levine, T P; Rabouille, C; Kieckbusch, R H; Warren, G

    1996-07-19

    The vesicle docking protein p115 showed saturable, high affinity binding to interphase Golgi membranes. The affinity of binding was up to 20-fold lower using membranes preincubated with mitotic cytosol. In contrast, binding was not affected by mitotic pretreatment of p115. The reduction in p115 binding was mediated by phosphorylation, could be induced by a cyclin-dependent kinase, and was fully reversible. A shift of p115 from membranes to cytosol was also found after fractionating mitotic cells. The functional significance of the decreased binding was addressed by in vitro mitotic incubations which disassemble Golgi cisternae, predominantly producing transport vesicles. The addition of excess p115 decreased loss of membrane from cisternae, indicating that p115's action is limiting while transport vesicles accumulate. The cessation of intra-Golgi traffic in mitosis has been hypothesized to result from an inhibition of membrane fusion while budding of transport vesicles continues. This process also contributes to mitotic Golgi disassembly. Our results imply that there is a mitotic modification to Golgi membranes leading to a reduction in the affinity of the p115 receptor. Reduced p115 binding may play a part in the inhibition of membrane fusion by preventing prior vesicle docking. PMID:8663393

  5. 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.

  6. Meiotic and Mitotic Recombination in Meiosis Kathryn P. Kohl* and Jeff Sekelsky*,,,1

    E-print Network

    Sekelsky, Jeff

    REVIEW Meiotic and Mitotic Recombination in Meiosis Kathryn P. Kohl* and Jeff Sekelsky*,,,1 evolved to incorporate special features unique to meiosis. MEIOSIS is essential to maintaining the proper replication with two rounds of cellular division, meiosis effectively halves the chromosome content

  7. Pretreatment in a high-pressure microwave processor for MIB-1 immunostaining of cytological smears and paraffin tissue sections to visualize the various phases of the mitotic cycle.

    PubMed

    Suurmeijer, A J; Boon, M E

    1999-08-01

    In many pathology laboratories, both microwave ovens and pressure cookers are used for pretreatment of cytologic smears and paraffin sections to allow MIB-1 staining. For both methods there are two problems. First, the results cannot be used for quantitation because standardization is impossible. Second, the staining results are often suboptimal, resulting in negative staining of cells in the G(1)- and S-phases. When pretreatment is performed in a microwave processor, allowing microwave heating under pressure, precise temperature monitoring becomes possible. In addition, the importance of the pH of the buffer was studied using a test battery series. Optimal staining is achieved at a temperature of 115C, 10 min, pH 6. This method proved to be highly reproducible. Because the immunostaining results are optimal, the various phases of the cell cycle can be defined in the sections and smears. In addition, the perinucleolar staining of the late G(1)-phase is optimally visualized and nuclei of the stable pKi-67 pathway can be identified. Under suboptimal conditions, in particular, the number of cells in the late G(1)-phase are underestimated in the MIB-1 counts. PMID:10424885

  8. INTRODUCTION Mitotic metaphase chromosomes show sister chromatids

    E-print Network

    Villefranche sur mer

    . Meiosis I bivalents, as mitotic chromosomes, show sister-chromatid centromere and arm cohesions cohesion during meiosis I, and then release centromere cohesion during meiosis II (for review see Moore and Orr- Weaver, 1998). Consequently, this sequential loss of cohesion during meiosis might be precisely

  9. Disruption of Mitotic Progression by Arsenic.

    PubMed

    States, J Christopher

    2015-07-01

    Arsenic is an enigmatic xenobiotic that causes a multitude of chronic diseases including cancer and also is a therapeutic with promise in cancer treatment. Arsenic causes mitotic delay and induces aneuploidy in diploid human cells. In contrast, arsenic causes mitotic arrest followed by an apoptotic death in a multitude of virally transformed cells and cancer cells. We have explored the hypothesis that these differential effects of arsenic exposure are related by arsenic disruption of mitosis and are differentiated by the target cell's ability to regulate or modify cell cycle checkpoints. Functional p53/CDKN1A axis has been shown to mitigate the mitotic block and to be essential to induction of aneuploidy. More recent preliminary data suggest that microRNA modulation of chromatid cohesion also may play a role in escape from mitotic block and in generation of chromosomal instability. Other recent studies suggest that arsenic may be useful in treatment of solid tumors when used in combination with other cytotoxic agents such as cisplatin. PMID:25796515

  10. Phosphoproteome analysis of the human mitotic spindle

    Microsoft Academic Search

    Marjaana Nousiainen; Herman H. W. Silljé; Guido Sauer; Erich A. Nigg; Roman Körner

    2006-01-01

    During cell division, the mitotic spindle segregates the sister chromatids into two nascent cells, such that each daughter cell inherits one complete set of chromosomes. Errors in spindle formation can result in both chromosome missegregation and cytokinesis defects and hence lead to genomic instability. To ensure the correct function of the spindle, the activity and localization of spindle associated proteins

  11. Mitotic Waves in Laticifers of Euphorbia marginata

    Microsoft Academic Search

    Paul Mahlberg; Pritam Sabharwal

    1966-01-01

    A successive pattern of nuclear divisions that result in mitotic waves has been observed within the coenocytic nonarticulated laticifers of embryos of Euphorbia marginata Pursh. These waves originate independently in the cotyledonary or hypocotyl portion of the laticifer and exhibit uni- or bi-directional movement at variable velocities. Individual nuclei or groups of neighoring nuclei in a laticifer were observed in

  12. Feature selection in finite mixture of sparse normal linear models in high-dimensional feature space.

    PubMed

    Khalili, Abbas; Chen, Jiahua; Lin, Shili

    2011-01-01

    Rapid advancement in modern technology has allowed scientists to collect data of unprecedented size and complexity. This is particularly the case in genomics applications. One type of statistical problem in such applications is concerned with modeling an output variable as a function of a small subset of a large number of features based on relatively small sample sizes, which may even be coming from multiple subpopulations. As such, selecting the correct predictive features (variables) for each subpopulation is the key. To address this issue, we consider the problem of feature selection in finite mixture of sparse normal linear (FMSL) models in large feature spaces. We propose a 2-stage procedure to overcome computational difficulties and large false discovery rates caused by the large model space. First, to deal with the curse of dimensionality, a likelihood-based boosting is designed to effectively reduce the number of candidate features. This is the key thrust of our new method. The greatly reduced set of features is then subjected to a sparsity inducing procedure via a penalized likelihood method. A novel scheme is also proposed for the difficult problem of finding good starting points for the expectation-maximization estimation of mixture parameters. We use an extended Bayesian information criterion to determine the final FMSL model. Simulation results indicate that the procedure is successful in selecting the significant features without including a large number of insignificant ones. A real data example on gene transcription regulation is also presented. PMID:20716532

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

    SciTech Connect

    Taylor, B. Frazier; McNeely, Samuel C.; Miller, Heather L. [Department of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202 (United States); States, J. Christopher [Department of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202 (United States)], E-mail: jcstates@louisville.edu

    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.

  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. 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 ?g/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

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

    PubMed

    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

    2009-06-01

    Fisetin is a natural flavonol present in edible vegetables, fruits and wine at 2-160 microg/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

  17. 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

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

    SciTech Connect

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

    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

  19. Two Mammalian Mitotic Aurora Kinases: Who's Who?

    NSDL National Science Digital Library

    Simon Descamps (Universite de Rennes I; Groupe Cycle Cellulaire and Genetique et Developpement REV)

    2001-03-13

    Several serine-threonine kinases related to the Ipl1p kinase in budding yeast, termed aurora kinases, have been cloned recently. Their characterization revealed them to be important regulators of mitotic functions, including (i) the separation of the centrosome, (ii) assembly of the spindles, and (iii) segregation of the chromosomes. The Perspective by Descamps and Prigent delves into the latest observations on aurora kinases in humans and the specific roles of each kinase within the process of mitosis.

  20. 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.

  1. 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.

  2. CDIKP: A Highly-Compact Local Feature Descriptor Yun-Ta Tsai, Quan Wang, Suya You

    E-print Network

    Shahabi, Cyrus

    the scale-invariant feature detection with a robust projection kernel technique to produce highly efficient the Harris detector with automatic scale selection to detect distinctive feature that is scale-invariantCDIKP: A Highly-Compact Local Feature Descriptor Yun-Ta Tsai, Quan Wang, Suya You Computer Science

  3. Effect of Cell Shape and Dimensionality on Spindle Orientation and Mitotic Timing

    PubMed Central

    Charnley, Mirren; Anderegg, Fabian; Holtackers, René; Textor, Marcus; Meraldi, Patrick

    2013-01-01

    The formation and orientation of the mitotic spindle is a critical feature of mitosis. The morphology of the cell and the spatial distribution and composition of the cells' adhesive microenvironment all contribute to dictate the position of the spindle. However, the impact of the dimensionality of the cells' microenvironment has rarely been studied. In this study we present the use of a microwell platform, where the internal surfaces of the individual wells are coated with fibronectin, enabling the three-dimensional presentation of adhesive ligands to single cells cultured within the microwells. This platform was used to assess the effect of dimensionality and cell shape in a controlled microenvironment. Single HeLa cells cultured in circular microwells exhibited greater tilting of the mitotic spindle, in comparison to cells cultured in square microwells. This correlated with an increase in the time required to align the chromosomes at the metaphase plate due to prolonged activation of the spindle checkpoint in an actin dependent process. The comparison to 2D square patterns revealed that the dimensionality of cell adhesions alone affected both mitotic timings and spindle orientation; in particular the role of actin varied according to the dimensionality of the cells' microenvironment. Together, our data revealed that cell shape and the dimensionality of the cells' adhesive environment impacted on both the orientation of the mitotic spindle and progression through mitosis. PMID:23825020

  4. Revertant somatic mosaicism by mitotic recombination in dyskeratosis congenita.

    PubMed

    Jongmans, Marjolijn C J; Verwiel, Eugene T P; Heijdra, Yvonne; Vulliamy, Tom; Kamping, Eveline J; Hehir-Kwa, Jayne Y; Bongers, Ernie M H F; Pfundt, Rolph; van Emst, Liesbeth; van Leeuwen, Frank N; van Gassen, Koen L I; Geurts van Kessel, Ad; Dokal, Inderjeet; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J L; Kuiper, Roland P

    2012-03-01

    Revertant mosaicism is an infrequently observed phenomenon caused by spontaneous correction of a pathogenic allele. We have observed such reversions caused by mitotic recombination of mutant TERC (telomerase RNA component) alleles in six patients from four families affected by dyskeratosis congenita (DC). DC is a multisystem disorder characterized by mucocutaneous abnormalities, dystrophic nails, bone-marrow failure, lung fibrosis, liver cirrhosis, and cancer. We identified a 4 nt deletion in TERC in a family with an autosomal-dominant form of DC. In two affected brothers without bone-marrow failure, sequence analysis revealed pronounced overrepresentation of the wild-type allele in blood cells, whereas no such skewing was observed in the other tissues tested. These observations suggest that this mosaic pattern might have resulted from somatic reversion of the mutated allele to the normal allele in blood-forming cells. SNP-microarray analysis on blood DNA from the two brothers indeed showed independent events of acquired segmental isodisomy of chromosome 3q, including TERC, indicating that the reversions must have resulted from mitotic recombination events. Subsequently, after developing a highly sensitive method of detecting mosaic homozygosity, we have found four additional cases with a mosaic-reversion pattern in blood cells; these four cases are part of a cohort of 17 individuals with germline TERC mutations. This shows that revertant mosaicism is a recurrent event in DC. This finding has important implications for improving diagnostic testing and understanding the variable phenotype of DC. PMID:22341970

  5. Mitotic recombination in yeast: isolation and characterization of mutants with enhances spontaneous mitotic gene conversion rates

    SciTech Connect

    Maloney, D.H.; Fogel, S.

    1980-04-01

    Semi-dominant mutants displaying greatly elevated levels of spontaneous mitotic recombination have been isolated in a disomic haploid strain of yeast heteroallelic at the arg4 locus. They are designated by the symbol MIC. The mutants variously exhibit associated sensitivity to uv and ionizing radiation and to methyl methanesulfonate, enhanced uv-induced mitotic recombiation, and enhanced spontaneous forward mutation rates. Possible enzyme defects and involvement in repair and editing of DNA are discussed. The mutants are expected to simplify the analysis of recombination pathways in yeast.

  6. Preparation of tomato meiotic pachytene and mitotic metaphase chromosomes suitable for fluorescence in situ hybridization (FISH)

    Microsoft Academic Search

    Xiao-Bo Zhong; J. Hans de Jong; Pim Zabel

    1996-01-01

    Fluorescencein situ hybridization (FISH) is an increasingly powerful tool with a variety of applications in both basic and applied research. With excellent genetic, cytogenetic and molecular maps available, the tomato genome provides a good model to benefit from the full potential of FISH. Tomato chromosomes at mitotic metaphase are small and not particularly suitable for high-resolution FISH. In contrast, chromosomes

  7. Mitotic errors in chromosome 21 of human preimplantation embryos are associated with non-viability

    Microsoft Academic Search

    M. G. Katz-Jaffe; A. O. Trounson; D. S. Cram

    2004-01-01

    Fluorescent in situ hybridization (FISH) studies of human preimplantation embryos have demonstrated a high proportion of chromosomal mosaicism. To investigate the different timings and nature of chromosomal mosaicism, we developed single cell multiplex fluorescent (FL)-PCR to distinguish meiotic and mitotic cell division errors. Chromosome 21 was investigated as the model chromosome as trisomy 21 (Down's syndrome) represents the most common

  8. Combining Multiple Features for High Performance Face Recognition System

    Microsoft Academic Search

    Ching-Han CHEN Chia-Te CHU

    2004-01-01

    Abstract-Thispaper,proposesthe combination multiple facial feature extraction methods,and probabilistic,neural,network for ,facial recognition. Firstly, we use horizontal projection of 2 -D image to obtain accumulated,energy profile signal. Secondly, we obtain the statistical distribution of facial gray images. Finally, we adopt wavelet transform to extract low frequency coefficients from 1-D energy profile signal and statistical distribution of face graylevel values asfeature vectors, which

  9. 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

  10. Mitotic recombination of chromosome 17 in astrocytomas

    SciTech Connect

    James, C.D.; Carlbom, E.; Nordenskjold, M.; Collins, V.P.; Cavenee, W.K. (Ludwig Institute for Cancer Research, Montreal (Canada))

    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.

  11. High manufacturability Cu multilevel interconnects featuring hybrid-NCS structure

    Microsoft Academic Search

    I. Sugiura; N. Misawa; S. Otsuka; N. Nishikawa; Y. Iba; F. Sugimoto; Y. Setta; H. Sakai; Y. Koura; K. Nakano; T. Karasawa; Y. Ohkura; T. Kouno; H. Watatani; Y. Nakata; Y. Mizushima; T. Suzuki; H. Kitada; N. Shimizu; S. Nakai; M. Nakaishi; S. Fukuyama; T. Nakamura; E. Yano; M. Miyajima; K. Watanabe

    2005-01-01

    We developed a 65-nm CMOS technology that could successfully integrate a novel porous low-k material, NCS. Using our nano-clustering technique, we obtained that NCS had a high compatibility between a very low dielectric constant and high framework strength. We successfully fabricated 11-levels Cu interconnects using hybrid-NCS structure. These interconnects had a high tolerance to the etching process and produced a

  12. On the road to cancer: aneuploidy and the mitotic checkpoint

    Microsoft Academic Search

    Beth A. A. Weaver; Geert J. P. L. Kops; Don W. Cleveland

    2005-01-01

    Abnormal chromosome content — also known as aneuploidy — is the most common characteristic of human solid tumours. It has therefore been proposed that aneuploidy contributes to, or even drives, tumour development. The mitotic checkpoint guards against chromosome mis-segregation by delaying cell-cycle progression through mitosis until all chromosomes have successfully made spindle-microtubule attachments. Defects in the mitotic checkpoint generate aneuploidy

  13. Mitotic drivers—inhibitors of the Aurora B Kinase

    Microsoft Academic Search

    Nicholas Keen; Stephen Taylor

    2009-01-01

    In this article we review the basis for current anti-mitotic, anti-cancer, therapy and the potential for Aurora B kinase inhibitors\\u000a as a new differentiated class of agents—“mitotic drivers”. We review the current understanding of Aurora B inhibition from\\u000a basic cell biology to inhibitors currently undergoing clinical trials.

  14. The Mitotic Spindle: A Self-Made Machine

    NSDL National Science Digital Library

    E. Karsenti (EMBL; Cell Biology and Biophysics Program)

    2001-10-19

    The mitotic spindle is a highly dynamic molecular machine composed of tubulin, motors, and other molecules. It assembles around the chromosomes and distributes the duplicated genome to the daughter cells during mitosis. The biochemical and physical principles that govern the assembly of this machine are still unclear. However, accumulated discoveries indicate that chromosomes play a key role. Apparently, they generate a local cytoplasmic state that supports the nucleation and growth of microtubules. Then soluble and chromosome-associated molecular motors sort them into a bipolar array. The emerging picture is that spindle assembly is governed by a combination of modular principles and that their relative contribution may vary in different cell types and in various organisms.

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

    PubMed

    Salmela, Anna-Leena; Pouwels, Jeroen; Kukkonen-Macchi, Anu; Waris, Sinikka; Toivonen, Pauliina; Jaakkola, Kimmo; Mäki-Jouppila, Jenni; Kallio, Lila; Kallio, Marko J

    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',5-dihydroxy-4',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. PMID:22227008

  16. The yeast polo kinase Cdc5 regulates the shape of the mitotic nucleus.

    PubMed

    Walters, Alison D; May, Christopher K; Dauster, Emma S; Cinquin, Bertrand P; Smith, Elizabeth A; Robellet, Xavier; D'Amours, Damien; Larabell, Carolyn A; Cohen-Fix, Orna

    2014-12-01

    Abnormal nuclear size and shape are hallmarks of aging and cancer. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or "flare," that encompasses the nucleolus. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provide the first evidence that polo kinase, a key regulator of mitosis, plays a role in regulating nuclear morphology and NE expansion. PMID:25454593

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

    SciTech Connect

    Salmela, Anna-Leena [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland) [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Turku Graduate School of Biomedical Sciences, Turku (Finland); Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Pouwels, Jeroen; Kukkonen-Macchi, Anu [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland)] [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Waris, Sinikka; Toivonen, Pauliina [Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland)] [Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Jaakkola, Kimmo [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland)] [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Maeki-Jouppila, Jenni [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland) [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Drug Discovery Graduate School, University of Turku (Finland); Kallio, Lila, E-mail: lila.kallio@vtt.fi [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland)] [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Kallio, Marko J. [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland) [VTT Technical Research Centre of Finland, Medical Biotechnology, P.O. Box 106, Turku (Finland); Turku Centre for Biotechnology, P.O. Box 123, University of Turku (Finland); Centre of Excellence for Translational Genome-Scale Biology, P.O. Box 106, Academy of Finland (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.

  18. 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

  19. Identification of a mitotic death signature in cancer cell lines

    PubMed Central

    Sakurikar, Nandini; Eichhorn, Joshua M.; Alford, Sarah E.; Chambers, Timothy C.

    2013-01-01

    This study examined the molecular mechanism of action of anti-mitotic drugs. The hypothesis was tested that death in mitosis occurs through sustained mitotic arrest with robust Cdk1 signaling causing complete phosphorylation of Mcl-1 and Bcl-xL, and conversely, that mitotic slippage is associated with incomplete phosphorylation of Mcl-1/Bcl-xL. The results, obtained from studying six different cancer cell lines, strongly support the hypothesis and identify for the first time a unique molecular signature for mitotic death. The findings represent an important advance in understanding anti-mitotic drug action and provide insight into cancer cell susceptibility to such drugs which has important clinical implications. PMID:24099917

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

    SciTech Connect

    Jin, Q.; Duggan, R.; Dasa, S.; Li, F.; Chen, L. (Biosciences Division)

    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.

  1. 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

  2. Identification of a mitotic death signature in cancer cell lines.

    PubMed

    Sakurikar, Nandini; Eichhorn, Joshua M; Alford, Sarah E; Chambers, Timothy C

    2014-02-28

    This study examined the molecular mechanism of action of anti-mitotic drugs. The hypothesis was tested that death in mitosis occurs through sustained mitotic arrest with robust Cdk1 signaling causing complete phosphorylation of Mcl-1 and Bcl-xL, and conversely, that mitotic slippage is associated with incomplete phosphorylation of Mcl-1/Bcl-xL. The results, obtained from studying six different cancer cell lines, strongly support the hypothesis and identify for the first time a unique molecular signature for mitotic death. The findings represent an important advance in understanding anti-mitotic drug action and provide insight into cancer cell susceptibility to such drugs which has important clinical implications. PMID:24099917

  3. Features of air conditioning systems with separation of a moisture on high pressure

    Microsoft Academic Search

    Yuriy Dyachenko; Alexander Chichindaev

    2000-01-01

    In activity the analysis of the literature, directional on study of features of activity of a AHRS with separation of a moisture on high pressure is executed. As a result of study of design features of a AHRS the describing systems of a sectional type are established four indication: 1) a way of cooling of air high-pressure; 2) a degree

  4. AN EVALUATION OF FEATURE LEARNING METHODS FOR HIGH RESOLUTION IMAGE CLASSIFICATION

    E-print Network

    Schindler, Konrad

    AN EVALUATION OF FEATURE LEARNING METHODS FOR HIGH RESOLUTION IMAGE CLASSIFICATION P. Tokarczyk*, J of urban areas in high-resolution images is even more challenging, because many relevant objects are small, land cover, feature, pattern, recognition ABSTRACT: Automatic image classification is one

  5. Video Retrieval Using High Level Features: Exploiting Query Matching and Confidence-Based Weighting

    Microsoft Academic Search

    Shi-yong Neo; Jin Zhao; Min-yen Kan; Tat-seng Chua

    2006-01-01

    Recent research in video retrieval has focused on automated, high- level feature indexing on shots or frames. One important application of such indexing is to support precise video retrieval. We report on extensions of this semantic indexing on news video retrieval. First, we utilize extensive query anal- ysis to relate various high-level features and query terms by matching the tex-

  6. 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.

  7. NAD(P)H:quinone oxidoreductase 1 (NQO1) localizes to the mitotic spindle in human cells.

    PubMed

    Siegel, David; Kepa, Jadwiga K; Ross, David

    2012-01-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) is an FAD containing quinone reductase that catalyzes the 2-electron reduction of a broad range of quinones. The 2-electron reduction of quinones to hydroquinones by NQO1 is believed to be a detoxification process since this reaction bypasses the formation of the highly reactive semiquinone. NQO1 is expressed at high levels in normal epithelium, endothelium and adipocytes as well as in many human solid tumors. In addition to its function as a quinone reductase NQO1 has been shown to reduce superoxide and regulate the 20 S proteasomal degradation of proteins including p53. Biochemical studies have indicated that NQO1 is primarily located in the cytosol, however, lower levels of NQO1 have also been found in the nucleus. In these studies we demonstrate using immunocytochemistry and confocal imaging that NQO1 was found associated with mitotic spindles in cells undergoing division. The association of NQO1 with the mitotic spindles was observed in many different human cell lines including nontransformed cells (astrocytes, HUVEC) immortalized cell lines (HBMEC, 16HBE) and cancer (pancreatic adenocarcinoma, BXPC3). Confocal analysis of double-labeling experiments demonstrated co-localization of NQO1with alpha-tubulin in mitotic spindles. In studies with BxPc-3 human pancreatic cancer cells the association of NQO1 with mitotic spindles appeared to be unchanged in the presence of NQO1 inhibitors ES936 or dicoumarol suggesting that NQO1 can associate with the mitotic spindle and still retain catalytic activity. Analysis of archival human squamous lung carcinoma tissue immunostained for NQO1 demonstrated positive staining for NQO1 in the spindles of mitotic cells. The purpose of this study is to demonstrate for the first time the association of the quinone reductase NQO1 with the mitotic spindle in human cells. PMID:22984577

  8. NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Localizes to the Mitotic Spindle in Human Cells

    PubMed Central

    Siegel, David; Kepa, Jadwiga K.; Ross, David

    2012-01-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) is an FAD containing quinone reductase that catalyzes the 2-electron reduction of a broad range of quinones. The 2-electron reduction of quinones to hydroquinones by NQO1 is believed to be a detoxification process since this reaction bypasses the formation of the highly reactive semiquinone. NQO1 is expressed at high levels in normal epithelium, endothelium and adipocytes as well as in many human solid tumors. In addition to its function as a quinone reductase NQO1 has been shown to reduce superoxide and regulate the 20 S proteasomal degradation of proteins including p53. Biochemical studies have indicated that NQO1 is primarily located in the cytosol, however, lower levels of NQO1 have also been found in the nucleus. In these studies we demonstrate using immunocytochemistry and confocal imaging that NQO1 was found associated with mitotic spindles in cells undergoing division. The association of NQO1 with the mitotic spindles was observed in many different human cell lines including nontransformed cells (astrocytes, HUVEC) immortalized cell lines (HBMEC, 16HBE) and cancer (pancreatic adenocarcinoma, BXPC3). Confocal analysis of double-labeling experiments demonstrated co-localization of NQO1with alpha-tubulin in mitotic spindles. In studies with BxPc-3 human pancreatic cancer cells the association of NQO1 with mitotic spindles appeared to be unchanged in the presence of NQO1 inhibitors ES936 or dicoumarol suggesting that NQO1 can associate with the mitotic spindle and still retain catalytic activity. Analysis of archival human squamous lung carcinoma tissue immunostained for NQO1 demonstrated positive staining for NQO1 in the spindles of mitotic cells. The purpose of this study is to demonstrate for the first time the association of the quinone reductase NQO1 with the mitotic spindle in human cells. PMID:22984577

  9. 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 PPAR?, CCAAT/enhancer binding protein ?, 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 PPAR?. 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 ? 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

  10. Detecting key structural features within highly recombined genes.

    PubMed

    Wertz, John E; McGregor, Karen F; Bessen, Debra E

    2007-01-26

    Many microorganisms exhibit high levels of intragenic recombination following horizontal gene transfer events. Furthermore, many microbial genes are subject to strong diversifying selection as part of the pathogenic process. A multiple sequence alignment is an essential starting point for many of the tools that provide fundamental insights on gene structure and evolution, such as phylogenetics; however, an accurate alignment is not always possible to attain. In this study, a new analytic approach was developed in order to better quantify the genetic organization of highly diversified genes whose alleles do not align. This BLAST-based method, denoted BLAST Miner, employs an iterative process that places short segments of highly similar sequence into discrete datasets that are designated "modules." The relative positions of modules along the length of the genes, and their frequency of occurrence, are used to identify sequence duplications, insertions, and rearrangements. Partial alleles of sof from Streptococcus pyogenes, encoding a surface protein under host immune selection, were analyzed for module content. High-frequency Modules 6 and 13 were identified and examined in depth. Nucleotide sequences corresponding to both modules contain numerous duplications and inverted repeats, whereby many codons form palindromic pairs. Combined with evidence for a strong codon usage bias, data suggest that Module 6 and 13 sequences are under selection to preserve their nucleic acid secondary structure. The concentration of overlapping tandem and inverted repeats within a small region of DNA is highly suggestive of a mechanistic role for Module 6 and 13 sequences in promoting aberrant recombination. Analysis of pbp2X alleles from Streptococcus pneumoniae, encoding cell wall enzymes that confer antibiotic resistance, supports the broad applicability of this tool in deciphering the genetic organization of highly recombined genes. BLAST Miner shares with phylogenetics the important predictive quality that leads to the generation of testable hypotheses based on sequence data. PMID:17257051

  11. Anomalous Raman features of silicon nanowires under high pressure

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Somnath; Churochkin, Dmitry; Erasmus, Rudolph M.

    2010-10-01

    The potential of silicon nanowires (SiNWs), (diameter <10 nm) to transform into rigid bundlelike structures with distinct phonon confinement under high pressure (?15 GPa), instead of amorphizing as per previous reports, is demonstrated using in situ Raman spectroscopy. The observed splitting of the second order transverse optical (2TO) Raman mode into 2TO(L) and 2TO(W) phonon modes at ?5 GPa establishes a highly anisotropic and mode-dependent pressure response of these SiNWs. Properties of these structures are superior compared to other nanostructured silicon and bulk-Si in terms of increased linear modulus, more localized phonon confinement, and less anharmonicity.

  12. Feature Modelling of High Resolution Remote Sensing Images Considering Spatial Autocorrelation

    NASA Astrophysics Data System (ADS)

    Chen, Y. X.; Qin, K.; Liu, Y.; Gan, S. Z.; Zhan, Y.

    2012-08-01

    To deal with the problem of spectral variability in high resolution satellite images, this paper focuses on the analysis and modelling of spatial autocorrelation feature. The semivariograms are used to model spatial variability of typical object classes while Getis statistic is used for the analysis of local spatial autocorrelation within the neighbourhood window determined by the range information of the semivariograms. Two segmentation experiments are conducted via the Fuzzy C-Means (FCM) algorithm which incorporates both spatial autocorrelation features and spectral features, and the experimental results show that spatial autocorrelation features can effectively improve the segmentation quality of high resolution satellite images.

  13. Statistical Challenges with High Dimensionality: Feature Selection in Knowledge Discovery

    Microsoft Academic Search

    Jianqing Fan; Runze Li

    2006-01-01

    Technological innovations have revolutionized the process of scientific research and knowledge discovery. The availability of massive data and challenges from frontiers of research and development have reshaped statistical thinking, data analysis and theoretical studies. The challenges of high-dimensionality arise in diverse fields of sciences and the humanities, ranging from computational biology and health studies to financial engineering and risk management.

  14. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes.

    PubMed

    You, Jianxin; Srinivasan, Viswanathan; Denis, Gerald V; Harrington, William J; Ballestas, Mary E; Kaye, Kenneth M; Howley, Peter M

    2006-09-01

    The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is required for viral episome maintenance in host cells during latent infection. Two regions of the protein have been implicated in tethering LANA/viral episomes to the host mitotic chromosomes, and LANA chromosome-binding sites are subjects of high interest. Because previous studies had identified bromodomain protein Brd4 as the mitotic chromosome anchor for the bovine papillomavirus E2 protein, which tethers the viral episomes to host mitotic chromosomes (J. You, J. L. Croyle, A. Nishimura, K. Ozato, and P. M. Howley, Cell 117:349-360, 2004, and J. You, M. R. Schweiger, and P. M. Howley, J. Virol. 79:14956-14961, 2005), we examined whether KSHV LANA interacts with Brd4. We found that LANA binds Brd4 in vivo and in vitro and that the binding is mediated by a direct protein-protein interaction between the ET (extraterminal) domain of Brd4 and a carboxyl-terminal region of LANA previously implicated in chromosome binding. Brd4 associates with mitotic chromosomes throughout mitosis and demonstrates a strong colocalization with LANA and the KSHV episomes on host mitotic chromosomes. Although another bromodomain protein, RING3/Brd2, binds to LANA in a similar fashion in vitro, it is largely excluded from the mitotic chromosomes in KSHV-uninfected cells and is partially recruited to the chromosomes in KSHV-infected cells. These data identify Brd4 as an interacting protein for the carboxyl terminus of LANA on mitotic chromosomes and suggest distinct functional roles for the two bromodomain proteins RING3/Brd2 and Brd4 in LANA binding. Additionally, because Brd4 has recently been shown to have a role in transcription, we examined whether Brd4 can regulate the CDK2 promoter, which can be transactivated by LANA. PMID:16940503

  15. 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

  16. Budding yeast Swe1 is involved in the control of mitotic spindle elongation and is regulated by Cdc14 phosphatase during mitosis.

    PubMed

    Raspelli, Erica; Cassani, Corinne; Chiroli, Elena; Fraschini, Roberta

    2015-01-01

    Cyclin-dependent kinase (Cdk1) activity is required for mitotic entry, and this event is restrained by an inhibitory phosphorylation of the catalytic subunit Cdc28 on a conserved tyrosine (Tyr(19)). This modification is brought about by the protein kinase Swe1 that inhibits Cdk1 activation thus blocking mitotic entry. Swe1 levels are regulated during the cell cycle, and they decrease during G2/M concomitantly to Cdk1 activation, which drives entry into mitosis. However, after mitotic entry, a pool of Swe1 persists, and we collected evidence that it is involved in controlling mitotic spindle elongation. We also describe that the protein phosphatase Cdc14 is implicated in Swe1 regulation; in fact, we observed that Swe1 dephosphorylation in vivo depends on Cdc14 that, in turn, is able to control its subcellular localization. In addition we show that the lack of Swe1 causes premature mitotic spindle elongation and that high levels of Swe1 block mitotic spindle elongation, indicating that Swe1 inhibits this process. Importantly, these effects are not dependent upon the role of in Cdk1 inhibition. These data fit into a model in which Cdc14 binds and inhibits Swe1 to allow timely mitotic spindle elongation. PMID:25406317

  17. 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

  18. Non-iridescent transmissive structural color filter featuring highly efficient transmission and high excitation purity.

    PubMed

    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?mm(2), 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

  19. Feature Shape and Elevation Based Road Classification and Extraction on High Spatial

    E-print Network

    Carbonara, Joaquin

    Feature Shape and Elevation Based Road Classification and Extraction on High Spatial Resolution consuming. This research is to explore the methodologies of recognizing shape and elevation characteristics processing, and a three dimensional DEM elevation filtering model to extract the road and street features

  20. Temporal Video Segmentation to Scenes Using High-Level Audiovisual Features

    Microsoft Academic Search

    Panagiotis Sidiropoulos; Vasileios Mezaris; Ioannis Kompatsiaris; Hugo Meinedo; Miguel Bugalho; Isabel Trancoso

    2011-01-01

    In this paper, a novel approach to video temporal decomposition into semantic units, termed scenes, is presented. In contrast to previous temporal segmentation approaches that employ mostly low-level visual or audiovisual features, we in- troduce a technique that jointly exploits low-level and high- level features automatically extracted from the visual and the auditory channel. This technique is built upon the

  1. MUSIC GENRE VISUALIZATION AND CLASSIFICATION EXPLOITING A SMALL SET OF HIGH-LEVEL SEMANTIC FEATURES

    Microsoft Academic Search

    Giorgio Prandi; Augusto Sarti; Stefano Tubaro

    2009-01-01

    In this paper a system for continuous analysis, visualization and classification of musical streams is proposed. The system performs visualization and classification task by means of three high-level, semantic features extracted computing a reduction on a multidi- mensional low-level feature vector through the usage of Gaussian Mixture Models. The visualization of the semantic characteristics of the audio stream has been

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

    PubMed

    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, it's 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

  3. A Mitotic GlcNAcylation/Phosphorylation Signaling Complex Alters the Posttranslational State of the Cytoskeletal Protein Vimentin

    PubMed Central

    Slawson, Chad; Lakshmanan, T.; Knapp, Spencer

    2008-01-01

    O-linked ?-N-acetylglucosamine (O-GlcNAc) is a highly dynamic intracellular protein modification responsive to stress, hormones, nutrients, and cell cycle stage. Alterations in O-GlcNAc addition or removal (cycling) impair cell cycle progression and cytokinesis, but the mechanisms are not well understood. Here, we demonstrate that the enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are in a transient complex at M phase with the mitotic kinase Aurora B and protein phosphatase 1. OGT colocalized to the midbody during telophase with Aurora B. Furthermore, these proteins coprecipitated with each other in a late mitotic extract. The complex was stable under Aurora inhibition; however, the total cellular levels of O-GlcNAc were increased and the localization of OGT was decreased at the midbody after Aurora inhibition. Vimentin, an intermediate filament protein, is an M phase substrate for both Aurora B and OGT. Overexpression of OGT or OGA led to defects in mitotic phosphorylation on multiple sites, whereas OGT overexpression increased mitotic GlcNAcylation of vimentin. OGA inhibition caused a decrease in vimentin late mitotic phosphorylation but increased GlcNAcylation. Together, these data demonstrate that the O-GlcNAc cycling enzymes associate with kinases and phosphatases at M phase to regulate the posttranslational status of vimentin. PMID:18653473

  4. CDK control of mitotic progression in Saccharomyces cerevisiae

    E-print Network

    Rahal, Rami S

    2008-01-01

    Mitotic cyclin-dependent kinases (CDKs) are best known for their essential functions in triggering entry into M-phase, where they have established roles in nuclear envelope breakdown, chromosome condensation, and Golgi ...

  5. 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

  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. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation

    Microsoft Academic Search

    Michael J. Hendzel; Yi Wei; Michael A. Mancini; Aaron Van Hooser; Tamara Ranalli; B. R. Brinkley; David P. Bazett-Jones; C. David Allis

    1997-01-01

    .   We have generated and characterized a novel site-specific antibody highly specific for the phosphorylated form of the amino-terminus\\u000a of histone H3 (Ser10). In this study, we used this antibody to examine in detail the relationship between H3 phosphorylation\\u000a and mitotic chromosome condensation in mammalian cells. Our results extend previous biochemical studies by demonstrating that\\u000a mitotic phosphorylation of H3 initiates

  8. Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness

    Microsoft Academic Search

    Truong-An Tran; Ludovic Gillet; Sébastien Roger; Pierre Besson; Edward White; Jean-Yves Le Guennec

    2009-01-01

    Taxol is widely used in breast cancer chemotherapy. Its effects are primarily attributed to its anti-mitotic activity. Microtubule perturbators also exert antimetastatic activities which cannot be explained solely by the inhibition of proliferation. Voltage-dependent sodium channels (NaV) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting NaV activity with tetrodotoxin

  9. The product of proliferation disrupter is concentrated at centromeres and required for mitotic chromosome condensation and cell proliferation in Drosophila.

    PubMed

    Török, T; Harvie, P D; Buratovich, M; Bryant, P J

    1997-01-15

    Homozygosity for a null mutation in the proliferation disrupter (prod) gene of Drosophila causes decreased mitotic index, defects of anaphase chromatid separation, and imperfect chromosome condensation in larval neuroblasts and other proliferating cell populations. The defective condensation is especially obvious near the centromeres. Mutant larvae show slow growth and massive cell death in proliferating cell populations, followed by late larval lethality. Loss of prod function in mitotic clones leads to the arrest of oogenesis in the ovary and defective cuticle formation in imaginal disc derivatives. The prod gene encodes a novel 301-amino-acid protein that is ubiquitously expressed and highly concentrated at the centric heterochromatin of the second and third mitotic chromosomes, as well as at > 400 euchromatic loci on polytene chromosomes. We propose that Prod is a nonhistone protein essential for chromosome condensation and that the chromosomal and developmental defects are caused by incomplete centromere condensation in prod mutants. PMID:9009204

  10. Systematic Phosphorylation Analysis of Human Mitotic Protein Complexes

    PubMed Central

    Hegemann, Björn; Hutchins, James R.A.; Hudecz, Otto; Novatchkova, Maria; Rameseder, Jonathan; Sykora, Martina M.; Liu, Sihan; Mazanek, Michael; Lénárt, Péter; Hériché, Jean-Karim; Poser, Ina; Kraut, Norbert; Hyman, Anthony A.; Yaffe, Michael B.; Mechtler, Karl; Peters, Jan-Michael

    2014-01-01

    Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphorylation. Although many mitotic phosphorylation events have been identified in proteome-scale mass spectrometry studies, information on how these phosphorylation sites are distributed within mitotic protein complexes and which kinases generate these phosphorylation sites is largely lacking. We used systematic protein-affinity purification combined with mass spectrometry to identify 1818 phosphorylation sites in more than 100 mitotic protein complexes. In many complexes the phosphorylation sites were concentrated on a few subunits, suggesting that these subunits serve as “switchboards” to relay the kinase-regulatory signals within the complexes. Consequent bioinformatic analyses identified potential kinase – substrate relationships for most of these sites. In a subsequent in-depth analysis of key mitotic regulatory complexes using the Aurora kinase B (AURKB) inhibitor Hesperadin and a new Pololike kinase (PLK1) inhibitor, BI 4834, we determined the kinase-dependency for 172 phosphorylation sites on 41 proteins. Combination of the results of the cellular studies with Scansite motif prediction enabled us to identify 14 sites on 6 proteins as direct candidate substrates of AURKB or PLK1. PMID:22067460

  11. Polymer Models of Meiotic and Mitotic Chromosomes

    PubMed Central

    Marko, John F.; Siggia, Eric D.

    1997-01-01

    Polymers tied together by constraints exhibit an internal pressure; this idea is used to analyze physical properties of the bottle-brush–like chromosomes of meiotic prophase that consist of polymer-like flexible chromatin loops, attached to a central axis. Using a minimal number of experimental parameters, semiquantitative predictions are made for the bending rigidity, radius, and axial tension of such brushes, and the repulsion acting between brushes whose bristles are forced to overlap. The retraction of lampbrush loops when the nascent transcripts are stripped away, the oval shape of diplotene bivalents between chiasmata, and the rigidity of pachytene chromosomes are all manifestations of chromatin pressure. This two-phase (chromatin plus buffer) picture that suffices for meiotic chromosomes has to be supplemented by a third constituent, a chromatin glue to understand mitotic chromosomes, and explain how condensation can drive the resolution of entanglements. This process resembles a thermal annealing in that a parameter (the affinity of the glue for chromatin and/or the affinity of the chromatin for buffer) has to be tuned to achieve optimal results. Mechanical measurements to characterize this protein–chromatin matrix are proposed. Finally, the propensity for even slightly chemically dissimilar polymers to phase separate (cluster like with like) can explain the apparent segregation of the chromatin into A+T- and G+C-rich regions revealed by chromosome banding. PMID:9362064

  12. 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

  13. "Artificial mitotic spindle" generated by dielectrophoresis and protein micropatterning supports bidirectional transport of kinesin-coated beads.

    PubMed

    Uppalapati, Maruti; Huang, Ying-Ming; Aravamuthan, Vidhya; Jackson, Thomas N; Hancock, William O

    2011-01-01

    The mitotic spindle is a dynamic assembly of microtubules and microtubule-associated proteins that controls the directed movement of chromosomes during cell division. Because proper segregation of the duplicated genome requires that each daughter cell receives precisely one copy of each chromosome, numerous overlapping mechanisms have evolved to ensure that every chromosome is transported to the cell equator during metaphase. However, due to the inherent redundancy in this system, cellular studies using gene knockdowns or small molecule inhibitors have an inherent limit in defining the sufficiency of precise molecular mechanisms as well as quantifying aspects of their mechanical performance. Thus, there exists a need for novel experimental approaches that reconstitute important aspects of the mitotic spindle in vitro. Here, we show that by microfabricating Cr electrodes on quartz substrates and micropatterning proteins on the electrode surfaces, AC electric fields can be used to assemble opposed bundles of aligned and uniformly oriented microtubules as found in the mitotic spindle. By immobilizing microtubule ends on each electrode, analogous to anchoring at centrosomes, solutions of motor or microtubule binding proteins can be introduced and their resulting dynamics analyzed. Using this "artificial mitotic spindle" we show that beads functionalized with plus-end kinesin motors move in an oscillatory manner analogous to the movements of chromosomes and severed chromosome arms during metaphase. Hence, features of directional instability, an established characteristic of metaphase chromosome dynamics, can be reconstituted in vitro using a pair of uniformly oriented microtubule bundles and a plus-end kinesin functionalized bead. PMID:21031221

  14. Dyskerin Localizes to the Mitotic Apparatus and Is Required for Orderly Mitosis in Human Cells

    PubMed Central

    Alawi, Faizan; Lin, Ping

    2013-01-01

    Dyskerin is a highly conserved, nucleolar RNA-binding protein with established roles in small nuclear ribonucleoprotein biogenesis, telomerase and telomere maintenance and precursor rRNA processing. Telomerase is functional during S phase and the bulk of rRNA maturation occurs during G1 and S phases; both processes are inactivated during mitosis. Yet, we show that during the course of cell cycle progression, human dyskerin expression peaks during G2/M in parallel with the upregulation of pro-mitotic factors. Dyskerin redistributed from the nucleolus in interphase cells to the perichromosomal region during prometaphase, metaphase and anaphase. With continued anaphase progression, dyskerin also localized to the cytoplasm within the mid-pole region. Loss of dyskerin function via siRNA-mediated depletion promoted G2/M accumulation and this was accompanied by an increased mitotic index and activation of the spindle assembly checkpoint. Live cell imaging further revealed an array of mitotic defects including delayed prometaphase progression, a significantly increased incidence of multi-polar spindles, and anaphase bridges culminating in micronucleus formation. Together, these findings suggest that dyskerin is a highly dynamic protein throughout the cell cycle and increases the repertoire of fundamental cellular processes that are disrupted by absence of its normal function. PMID:24303026

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

    PubMed Central

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

    2013-01-01

    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 Liquid Chromatography (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 non-parametric 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

  16. An unsupervised feature extraction method for high dimensional image data compaction

    NASA Technical Reports Server (NTRS)

    Ghassemian, Hassan; Landgrebe, David

    1987-01-01

    A new on-line unsupervised feature extraction method for high-dimensional remotely sensed image data compaction is presented. This method can be utilized to solve the problem of data redundancy in scene representation by satellite-borne high resolution multispectral sensors. The algorithm first partitions the observation space into an exhaustive set of disjoint objects. Then, pixels that belong to an object are characterized by an object feature. Finally, the set of object features is used for data transmission and classification. The example results show that the performance with the compacted features provides a slight improvement in classification accuracy instead of any degradation. Also, the information extraction method does not need to be preceded by a data decompaction.

  17. High quality machine-robust image features: Identification in nonsmall cell lung cancer computed tomography images

    PubMed Central

    Hunter, Luke A.; Krafft, Shane; Stingo, Francesco; Choi, Haesun; Martel, Mary K.; Kry, Stephen F.; Court, Laurence E.

    2013-01-01

    Purpose: For nonsmall cell lung cancer (NSCLC) patients, quantitative image features extracted from computed tomography (CT) images can be used to improve tumor diagnosis, staging, and response assessment. For these findings to be clinically applied, image features need to have high intra and intermachine reproducibility. The objective of this study is to identify CT image features that are reproducible, nonredundant, and informative across multiple machines. Methods: Noncontrast-enhanced, test-retest CT image pairs were obtained from 56 NSCLC patients imaged on three CT machines from two institutions. Two machines (“M1” and “M2”) used cine 4D-CT and one machine (“M3”) used breath-hold helical 3D-CT. Gross tumor volumes (GTVs) were semiautonomously segmented then pruned by removing voxels with CT numbers less than a prescribed Hounsfield unit (HU) cutoff. Three hundred and twenty eight quantitative image features were extracted from each pruned GTV based on its geometry, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix. For each machine, features with concordance correlation coefficient values greater than 0.90 were considered reproducible. The Dice similarity coefficient (DSC) and the Jaccard index (JI) were used to quantify reproducible feature set agreement between machines. Multimachine reproducible feature sets were created by taking the intersection of individual machine reproducible feature sets. Redundant features were removed through hierarchical clustering based on the average correlation between features across multiple machines. Results: For all image types, GTV pruning was found to negatively affect reproducibility (reported results use no HU cutoff). The reproducible feature percentage was highest for average images (M1 = 90.5%, M2 = 94.5%, M1?M2 = 86.3%), intermediate for end-exhale images (M1 = 75.0%, M2 = 71.0%, M1?M2 = 52.1%), and lowest for breath-hold images (M3 = 61.0%). Between M1 and M2, the reproducible feature sets generated from end-exhale images were relatively machine-sensitive (DSC = 0.71, JI = 0.55), and the reproducible feature sets generated from average images were relatively machine-insensitive (DSC = 0.90, JI = 0.87). Histograms of feature pair correlation distances indicated that feature redundancy was machine-sensitive and image type sensitive. After hierarchical clustering, 38 features, 28 features, and 33 features were found to be reproducible and nonredundant for M1?M2 (average images), M1?M2 (end-exhale images), and M3, respectively. When blinded to the presence of test-retest images, hierarchical clustering showed that the selected features were informative by correctly pairing 55 out of 56 test-retest images using only their reproducible, nonredundant feature set values. Conclusions: Image feature reproducibility and redundancy depended on both the CT machine and the CT image type. For each image type, the authors found a set of cross-machine reproducible, nonredundant, and informative image features that would be useful for future image-based models. Compared to end-exhale 4D-CT and breath-hold 3D-CT, average 4D-CT derived image features showed superior multimachine reproducibility and are the best candidates for clinical correlation. PMID:24320527

  18. An Evaluation of Feature Learning Methods for High Resolution Image Classification

    NASA Astrophysics Data System (ADS)

    Tokarczyk, P.; Montoya, J.; Schindler, K.

    2012-07-01

    Automatic image classification is one of the fundamental problems of remote sensing research. The classification problem is even more challenging in high-resolution images of urban areas, where the objects are small and heterogeneous. Two questions arise, namely which features to extract from the raw sensor data to capture the local radiometry and image structure at each pixel or segment, and which classification method to apply to the feature vectors. While classifiers are nowadays well understood, selecting the right features remains a largely empirical process. Here we concentrate on the features. Several methods are evaluated which allow one to learn suitable features from unlabelled image data by analysing the image statistics. In a comparative study, we evaluate unsupervised feature learning with different linear and non-linear learning methods, including principal component analysis (PCA) and deep belief networks (DBN). We also compare these automatically learned features with popular choices of ad-hoc features including raw intensity values, standard combinations like the NDVI, a few PCA channels, and texture filters. The comparison is done in a unified framework using the same images, the target classes, reference data and a Random Forest classifier.

  19. Local-Learning-Based Feature Selection for High-Dimensional Data Analysis

    PubMed Central

    Sun, Yijun; Todorovic, Sinisa; Goodison, Steve

    2012-01-01

    This paper considers feature selection for data classification in the presence of a huge number of irrelevant features. We propose a new feature-selection algorithm that addresses several major issues with prior work, including problems with algorithm implementation, computational complexity, and solution accuracy. The key idea is to decompose an arbitrarily complex nonlinear problem into a set of locally linear ones through local learning, and then learn feature relevance globally within the large margin framework. The proposed algorithm is based on well-established machine learning and numerical analysis techniques, without making any assumptions about the underlying data distribution. It is capable of processing many thousands of features within minutes on a personal computer while maintaining a very high accuracy that is nearly insensitive to a growing number of irrelevant features. Theoretical analyses of the algorithm’s sample complexity suggest that the algorithm has a logarithmical sample complexity with respect to the number of features. Experiments on 11 synthetic and real-world data sets demonstrate the viability of our formulation of the feature-selection problem for supervised learning and the effectiveness of our algorithm. PMID:20634556

  20. FEATURE BASED FUSION OF MULTISENSOR DATA - INCLUSION OF HYPERSPECTRAL DATA INTO CLASSIFICATION OF HIGH RESOLUTION ORTHOPHOTOS

    Microsoft Academic Search

    A. Greiwe

    Many applications of remote sensing - like for example urban monitoring - require high resolution data. For a correct determination of object geometry, high spatial resolution data is essential. These data contain often low spectral information like three band RGB orthophotos. Similar feature values for thematic classes like water, dark pavements or dark rooftops lead to classification errors. As a

  1. Mining High-Level Features from Video Using Associations and Correlations

    Microsoft Academic Search

    Lin Lin; Mei-ling Shyu

    2009-01-01

    Association rule mining (ARM) has been studied in the areas of content-based multimedia retrieval and semantic concept detection due to its high efficiency and accuracy. Two important processes in mining the association rules for classification are rule generation and rule selection. In this paper, a novel high-level feature detection framework using the ARM technique together with the correlations among the

  2. Pores and ridges: high-resolution fingerprint matching using level 3 features.

    PubMed

    Jain, Anil K; Chen, Yi; Demirkus, Meltem

    2007-01-01

    Fingerprint friction ridge details are generally described in a hierarchical order at three different levels, namely, Level 1 (pattern), Level 2 (minutia points), and Level 3 (pores and ridge contours). Although latent print examiners frequently take advantage of Level 3 features to assist in identification, Automated Fingerprint Identification Systems (AFIS) currently rely only on Level 1 and Level 2 features. In fact, the Federal Bureau of Investigation's (FBI) standard of fingerprint resolution for AFIS is 500 pixels per inch (ppi), which is inadequate for capturing Level 3 features, such as pores. With the advances in fingerprint sensing technology, many sensors are now equipped with dual resolution (500 ppi/1,000 ppi) scanning capability. However, increasing the scan resolution alone does not necessarily provide any performance improvement in fingerprint matching, unless an extended feature set is utilized. As a result, a systematic study to determine how much performance gain one can achieve by introducing Level 3 features in AFIS is highly desired. We propose a hierarchical matching system that utilizes features at all the three levels extracted from 1,000 ppi fingerprint scans. Level 3 features, including pores and ridge contours, are automatically extracted using Gabor filters and wavelet transform and are locally matched using the Iterative Closest Point (ICP) algorithm. Our experiments show that Level 3 features carry significant discriminatory information. There is a relative reduction of 20 percent in the equal error rate (EER) of the matching system when Level 3 features are employed in combination with Level 1 and 2 features. This significant performance gain is consistently observed across various quality fingerprint images. PMID:17108380

  3. 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, ? 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

  4. 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.

  5. Relative contributions of chromatin and kinetochores to mitotic spindle assembly

    PubMed Central

    Lon?arek, Jadranka; Kaláb, Petr; Khodjakov, Alexey

    2009-01-01

    During mitosis and meiosis in animal cells, chromosomes actively participate in spindle assembly by generating a gradient of Ran guanosine triphosphate (RanGTP). A high concentration of RanGTP promotes microtubule nucleation and stabilization in the vicinity of chromatin. However, the relative contributions of chromosome arms and centromeres/kinetochores in this process are not known. In this study, we address this issue using cells undergoing mitosis with unreplicated genomes (MUG). During MUG, chromatin is rapidly separated from the forming spindle, and both centrosomal and noncentrosomal spindle assembly pathways are active. MUG chromatin is coated with RCC1 and establishes a RanGTP gradient. However, a robust spindle forms around kinetochores/centromeres outside of the gradient peak. When stable kinetochore microtubule attachment is prevented by Nuf2 depletion in both MUG and normal mitosis, chromatin attracts astral microtubules but cannot induce spindle assembly. These results support a model in which kinetochores play the dominant role in the chromosome-mediated pathway of mitotic spindle assembly. PMID:19805628

  6. 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

  7. 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

  8. 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

  9. MYC Is a Major Determinant of Mitotic Cell Fate.

    PubMed

    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

    2015-07-13

    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

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

    PubMed

    Kschonsak, Marc; Haering, Christian H

    2015-07-01

    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

  11. High-resolution multispectral satellite image matching using scale invariant feature transform and speeded up robust features

    NASA Astrophysics Data System (ADS)

    Teke, Mustafa; Vural, M. Firat; Temizel, Alptekin; Yard?mc?, Yasemin

    2011-01-01

    Satellite images captured in different spectral bands might exhibit nonlinear intensity changes at the corresponding spatial locations due to the different reflectance responses for these bands. This affects the image registration performance negatively as the corresponding features might have different properties in different bands. We propose a modification to the widely used scale invariant feature transform (SIFT) method to increase the correct feature matching ratio and to decrease the computation time of this algorithm for the multispectral satellite images. We also apply scale restriction to SIFT and speeded up robust features (SURF) algorithms to increase the correct match ratio. We present test results for variations of SIFT and SURF algorithms. The results show the effectiveness of the proposed improvements compared to the other SIFT- and SURF-based methods.

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

    Microsoft Academic Search

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

    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,

  13. Low and High-Level Visual Feature Based Apple Detection from Multi-modal Images

    E-print Network

    Wachs, Juan

    1 Low and High-Level Visual Feature Based Apple Detection from Multi-modal Images J. P. Wachs1 , H discusses the development of a machine vision system, capable of recognizing occluded green apples within a tree canopy. This involves the detection of "green" apples within scenes of "green leaves", shadow

  14. Using Depth and Appearance Features for Informed Robot Grasping of Highly Wrinkled Clothes

    E-print Network

    Moreno-Noguer, Francesc

    Using Depth and Appearance Features for Informed Robot Grasping of Highly Wrinkled Clothes Arnau is a key problem in cloth manipulation. Most current approaches follow a multiple re- grasp strategy for this purpose, in which clothes are sequentially grasped from different points until one of them yields

  15. Immersion Scatterometry for Improved Feature Resolution and High Speed Acquisition of Resist Profiles

    E-print Network

    Terry, Fred L.

    Immersion Scatterometry for Improved Feature Resolution and High Speed Acquisition of Resist and control in lithography and etch processes. Experimental real-time, in situ demonstrations of critical dimension monitoring and control have been made for reactive ion etching. There have been no similar

  16. Classification of epilepsy using high-order spectra features and principle component analysis.

    PubMed

    Du, Xian; Dua, Sumeet; Acharya, Rajendra U; Chua, Chua Kuang

    2012-06-01

    The classification of epileptic electroencephalogram (EEG) signals is challenging because of high nonlinearity, high dimensionality, and hidden states in EEG recordings. The detection of the preictal state is difficult due to its similarity to the ictal state. We present a framework for using principal components analysis (PCA) and a classification method for improving the detection rate of epileptic classes. To unearth the nonlinearity and high dimensionality in epileptic signals, we extract principal component features using PCA on the 15 high-order spectra (HOS) features extracted from the EEG data. We evaluate eight classifiers in the framework using true positive (TP) rate and area under curve (AUC) of receiver operating characteristics (ROC). We show that a simple logistic regression model achieves the highest TP rate for class "preictal" at 97.5% and the TP rate on average at 96.8% with PCA variance percentages selected at 100%, which also achieves the most AUC at 99.5%. PMID:21222222

  17. Subunit structure of chromosomes in mitotic nuclei of physarum polycephalum.

    PubMed

    Hozier, J C; Kaus, R

    1976-08-01

    We have investigated the subunit structure of mitotic chromosomes of the acellular slime mould Physarum polycephalum, using the nuclease susceptibility of isolated mitotic nuclei as a probe. A characteristic pattern of DNA digestion products is obtained, containing approximately integral multiples of a basic 140 base pair DNA segment that resembles very closely the pattern in G2 phase nuclei of Physarum and of calf lymphocyte nuclei. These results demonstrate that during the process of chromosome condensation there is no alteration at the primary level of chromatin structure that is responsible for the characteristic DNA digestion pattern. PMID:986286

  18. 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.

  19. ?-Tubulin Plays an Essential Role in the Coordination of Mitotic Events

    E-print Network

    Prigozhina, Natalie L.; Oakley, C. Elizabeth; Lewis, Amanda M.; Nayak, Tania; Osmani, Stephen A.; Oakley, Berl R.

    2004-03-01

    mitotic events (anaphase A, anaphase B, and chromosomal disjunction) and nuclei reentered interphase quickly even though mitosis was not completed successfully. Time-lapse microscopy also revealed that transient mitotic spindle abnormalities, in particular...

  20. 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

  1. 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

  2. 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; Teixidó, Nuria; Rossi, Sergio; López-González, 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.

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

    NASA Astrophysics Data System (ADS)

    Ta?kin Kaya, Gül?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.

  4. A Time-Series Method for Automated Measurement of Changes in Mitotic and Interphase Duration from Time-Lapse Movies

    PubMed Central

    Li, Fuhai; Zhou, Xiaobo; Wong, Stephen T. C.; King, Randall W.

    2011-01-01

    Background Automated time-lapse microscopy can visualize proliferation of large numbers of individual cells, enabling accurate measurement of the frequency of cell division and the duration of interphase and mitosis. However, extraction of quantitative information by manual inspection of time-lapse movies is too time-consuming to be useful for analysis of large experiments. Methodology/Principal Findings Here we present an automated time-series approach that can measure changes in the duration of mitosis and interphase in individual cells expressing fluorescent histone 2B. The approach requires analysis of only 2 features, nuclear area and average intensity. Compared to supervised learning approaches, this method reduces processing time and does not require generation of training data sets. We demonstrate that this method is as sensitive as manual analysis in identifying small changes in interphase or mitotic duration induced by drug or siRNA treatment. Conclusions/Significance This approach should facilitate automated analysis of high-throughput time-lapse data sets to identify small molecules or gene products that influence timing of cell division. PMID:21966537

  5. HyaluronanCD44 pathway regulates orientation of mitotic spindle in normal epithelial cells

    Microsoft Academic Search

    Takeshi Fujiwara; Tomomi Kawakatsu; Sayaka Tayama; Yasuyo Kobayashi; Nobuo Sugiura; Koji Kimata; Yoshimi Takai

    2008-01-01

    Orientation of mitotic spindle and cell division axis can impact normal physiological processes, including epithelial tissue branching and neuron generation by asymmetric cell division. Micro- tubule dynamics and its interaction with cortical proteins regulate the orientation of mitotic spindle axis. However, the nature of extracellular signals that control proper orientation of mitotic spindle axis is largely unclear. Here, we show

  6. High-Velocity Features of Calcium and Silicon in the Spectra of Type Ia Supernovae

    E-print Network

    Silverman, Jeffrey M; Marion, G H; Wheeler, J Craig; Barna, Barnabas; Szalai, Tamas; Mulligan, Brian; Filippenko, Alexei V

    2015-01-01

    "High-velocity features" (HVFs) are spectral features in Type Ia supernovae (SNe Ia) that have minima indicating significantly higher (by greater than about 6000 km/s) velocities than typical "photospheric-velocity features" (PVFs). The PVFs are absorption features with minima indicating typical photospheric (i.e., bulk ejecta) velocities (usually ~9000-15,000 km/s near B-band maximum brightness). In this work we undertake the most in-depth study of HVFs ever performed. The dataset used herein consists of 445 low-resolution optical and near-infrared (NIR) spectra (at epochs up to 5 d past maximum brightness) of 210 low-redshift SNe Ia that follow the "Phillips relation." A series of Gaussian functions is fit to the data in order to characterise possible HVFs of Ca II H&K, Si II {\\lambda}6355, and the Ca II NIR triplet. The temporal evolution of the velocities and strengths of the PVFs and HVFs of these three spectral features is investigated, as are possible correlations with other SN Ia observables. We f...

  7. High-resolution face verification using pore-scale facial features.

    PubMed

    Li, Dong; Zhou, Huiling; Lam, Kin-Man

    2015-08-01

    Face recognition methods, which usually represent face images using holistic or local facial features, rely heavily on alignment. Their performances also suffer a severe degradation under variations in expressions or poses, especially when there is one gallery per subject only. With the easy access to high-resolution (HR) face images nowadays, some HR face databases have recently been developed. However, few studies have tackled the use of HR information for face recognition or verification. In this paper, we propose a pose-invariant face-verification method, which is robust to alignment errors, using the HR information based on pore-scale facial features. A new keypoint descriptor, namely, pore-Principal Component Analysis (PCA)-Scale Invariant Feature Transform (PPCASIFT)-adapted from PCA-SIFT-is devised for the extraction of a compact set of distinctive pore-scale facial features. Having matched the pore-scale features of two-face regions, an effective robust-fitting scheme is proposed for the face-verification task. Experiments show that, with one frontal-view gallery only per subject, our proposed method outperforms a number of standard verification methods, and can achieve excellent accuracy even the faces are under large variations in expression and pose. PMID:25781876

  8. Role of senescence and mitotic catastrophe in cancer therapy

    Microsoft Academic Search

    Richa Singh; Jasmine George; Yogeshwer Shukla

    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

  9. 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 ?-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 ?-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

  10. Mitotic cycles in human cell strains with sex chromosomes aneuploidy

    Microsoft Academic Search

    V. I. Kukharenko; K. N. Grinberg; A. M. Kuliev

    1978-01-01

    A persistence of the embryonic type of mitotic cycle was found in postnatal strains with aneuploidy of sex chromosomes (45,X; 47,XXX; 49,XXXXX;47,XYY;49,XXXXY). Life-span and proliferating activity of the strains did not differ from those of diploid postnatal cells.

  11. Mitotic spindle orientation: semaphorin-plexin signaling flags the way.

    PubMed

    Humbert, Patrick O; Gödde, Nathan J

    2015-05-01

    The extracellular signals and corresponding receptors that align the mitotic spindle of symmetrically dividing cells within an epithelial sheet are largely unknown. In this issue of Developmental Cell, Xia et al. (2015) identify semaphorin-plexin signaling as a regulator of spindle orientation critical for kidney development and repair. PMID:25942620

  12. Genetic algorithm-based feature selection in high-resolution NMR spectra

    PubMed Central

    Cho, Hyun-Woo; Jeong, Myong K.; Park, Youngja; Ziegler, Thomas R.; Jones, Dean P.

    2011-01-01

    High-resolution nuclear magnetic resonance (NMR) spectroscopy has provided a new means for detection and recognition of metabolic changes in biological systems in response to pathophysiological stimuli and to the intake of toxins or nutrition. To identify meaningful patterns from NMR spectra, various statistical pattern recognition methods have been applied to reduce their complexity and uncover implicit metabolic patterns. In this paper, we present a genetic algorithm (GA)-based feature selection method to determine major metabolite features to play a significant role in discrimination of samples among different conditions in high-resolution NMR spectra. In addition, an orthogonal signal filter was employed as a preprocessor of NMR spectra in order to remove any unwanted variation of the data that is unrelated to the discrimination of different conditions. The results of k-nearest neighbors and the partial least squares discriminant analysis of the experimental NMR spectra from human plasma showed the potential advantage of the features obtained from GA-based feature selection combined with an orthogonal signal filter. PMID:21472035

  13. High-Velocity Absorption Features in FUSE Spectra of Eta Carinae

    NASA Technical Reports Server (NTRS)

    Sonneborn, G.; Iping, R. C.; Gull, T. R.; Vieira, G.

    2003-01-01

    Numerous broad (200 to 1000 km/sec) features in the FUSE spectrum (905-1187 A) of eta Carinae are identified as absorption by a forest of high-velocity narrow lines formed in the expanding circumstellar envelope. These features were previously thought to be P-Cygni lines arising in the wind of the central star. The features span a heliocentric velocity range of -140 to -580 km/sec and are seen prominently in low-ionization ground-state transitions (e.g. N I 1134-35, Fe II 1145-42, 1133, 1127- 22, P II 1153, C I 1158) in addition to C III] 1176 A. The high-velocity components of the FUSE transitions have depths about 50% below the continuum. The identifications are consistent with the complex velocity structures seen in ground- and excited-state transitions of Mg I, Mg 11, Fe II, V II, etc observed in STIS/E230H spectra. The origin of other broad features of similar width and depth in the FUSE spectrum, but without low-velocity ISM absorption, are unidentified. However, they are suspected of being absorption of singly-ionized iron-peak elements (e.g. Fe II, V II, Cr II) out of excited levels 1,000 to 20,000 cmE-l above the ground state. The high-velocity features seen in Fe II 1145 are also present in Fe II 1608 (STIS/E140M), but are highly saturated in the latter. Since these transitions have nearly identical log (flambda) (1.998 vs. 2.080), the differences in the profiles are attributable to the different aperture sizes used (30 x 30 arcsec for FUSE, 0.2 x 0.2 arcsec for STIS/E140M). The high-velocity gas appears to be very patchy or has a small covering factor near the central star. Eta Carinae has been observed several times by FUSE over the past three years. The FUSE flux levels and spectral features in eta Car are essentially unchanged over the 2000 March to June 2002 period, establishing a baseline far-UV spectrum in advance of the predicted spectroscopic minimum in 2003.

  14. Mitotic regulation of fungal cell-to-cell connectivity through septal pores involves the NIMA kinase

    PubMed Central

    Shen, Kuo-Fang; Osmani, Aysha H.; Govindaraghavan, Meera; Osmani, Stephen A.

    2014-01-01

    Intercellular bridges are a conserved feature of multicellular organisms. In multicellular fungi, cells are connected directly via intercellular bridges called septal pores. Using Aspergillus nidulans, we demonstrate for the first time that septal pores are regulated to be opened during interphase but closed during mitosis. Septal pore–associated proteins display dynamic cell cycle–regulated locations at mature septa. Of importance, the mitotic NIMA kinase locates to forming septa and surprisingly then remains at septa throughout interphase. However, during mitosis, when NIMA transiently locates to nuclei to promote mitosis, its levels at septa drop. A model is proposed in which NIMA helps keep septal pores open during interphase and then closed when it is removed from them during mitosis. In support of this hypothesis, NIMA inactivation is shown to promote interphase septal pore closing. Because NIMA triggers nuclear pore complex opening during mitosis, our findings suggest that common cell cycle regulatory mechanisms might control septal pores and nuclear pores such that they are opened and closed out of phase to each other during cell cycle progression. The study provides insights into how and why cytoplasmically connected Aspergillus cells maintain mitotic autonomy. PMID:24451264

  15. Liquid fuel ignition features during its spilling on the metallic substrate heated up to high temperatures

    NASA Astrophysics Data System (ADS)

    Vysokomornaya, Olga; Scherbinina, Anastasia; Strizhak, Pavel

    2015-01-01

    Forecasting heat and mass transfer model for the numerical investigation of liquid fuel ignition features during its spilling on the metallic substrate heated up to high temperatures was developed. The dependences of liquid fuel (by the example of kerosene) ignition delay times on the velocity of its spilling, the liquid film (which is formed) thickness and the metallic substrate temperature were found. The least values of these parameters (whereby the ignition is possible under the heat and mass transfer conditions considered) were determined.

  16. New features in Saturn's atmosphere revealed by high-resolution thermal infrared images

    NASA Technical Reports Server (NTRS)

    Gezari, D. Y.; Mumma, M. J.; Espenak, F.; Deming, D.; Bjoraker, G.; Woods, L.; Folz, W.

    1989-01-01

    Observations of the stratospheric IR emission structure on Saturn are presented. The high-spatial-resolution global images show a variety of new features, including a narrow equatorial belt of enhanced emission at 7.8 micron, a prominent symmetrical north polar hotspot at all three wavelengths, and a midlatitude structure which is asymmetrically brightened at the east limb. The results confirm the polar brightening and reversal in position predicted by recent models for seasonal thermal variations of Saturn's stratosphere.

  17. IMAGE REGISTRATION OF HIGH RESOLUTION REMOTE SENSING BASED ON STRAIGHT LINE FEATURE

    Microsoft Academic Search

    Gong Danchao; Tang Xiaotao; Li Shizhong; Hu Guojun

    Aim at registration of high resolution remote sensing images,a image registration algorithm based on line feature is described in this paper. First,the lines in both images are extracted, Next a modified iterated Hough transform is introduced to develop the correspondence of lines . Finally,the parameters of affine registration transformation functions were calculated ,based on the Similarity Measure of the distance

  18. Investigations into high resolution mapping of precipitation features utilizing the TRMM precipitation Radar

    Microsoft Academic Search

    Chris Kidd; John Kwiatkowski; Steve Nesbitt

    2010-01-01

    Precipitation measurements from the Tropical Rainfall Measuring Mission (TRMM) satellite's Precipitation Radar (PR) have been used to create high-resolution grids of precipitation features at a resolution of 0.05degrees. This grid size is on the order of a nominal PR instantaneous field of view (ifov) of 4.9km at nadir. Currently 12 years of data has been collected from the TRMM mission,

  19. GENRE CLASSIFICATION USING BASS-RELATED HIGH-LEVEL FEATURES AND PLAYING STYLES

    Microsoft Academic Search

    Hanna Lukashevich; Christian Dittmar; Gerald Schuller

    2009-01-01

    Considering its mediation role between the poles of rhythm, harmony, and melody, the bass plays a crucial role in most music genres. This paper introduces a novel set of transcription-based high-level features that characteri ze the bass and its interaction with other participating instrume nts. Furthermore, a new method to model and automatically retrieve different genre-specific bass playing styles is

  20. 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.

  1. 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. [InsituTec Inc., 2750 East W.T. Harris Boulevard, Suite 103, Charlotte, North Carolina 28213 and Center for Precision Metrology, UNCC, 9201 University City Boulevard, Charlotte, North Carolina 28213 (United States); Center for Precision Metrology, UNCC, 9201 University City Boulevard, Charlotte, North Carolina 28213 (United States); InsituTec Inc., 2750 East W.T. Harris Boulevard, Suite 103, Charlotte, North Carolina 28213 (United States)

    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.

  2. Down-modulation of nucleoporin RanBP2/Nup358 impaired chromosomal alignment and induced mitotic catastrophe.

    PubMed

    Hashizume, C; Kobayashi, A; Wong, R W

    2013-01-01

    Chromosomal missegregation is a common feature of many human tumors. Recent studies have indicated a link between nucleoporin RanBP2/Nup358 and chromosomal segregation during mitosis; however, the molecular details have yet to be fully established. Observed through live cell imaging and flow cytometry, here we show that RNA interference-mediated knockdown of RanBP2 induced G2/M phase arrest, metaphase catastrophe and mitotic cell death. Furthermore, RanBP2 down-modulation disrupted importin/karyopherin ?1 as well as the expression and localization of the Ran GTPase activating protein 1. We found that N-terminal of RanBP2 interacted with the N-terminal of importin ?1. Moreover, at least a portion of RanBP2 partially localizes at the centrosome during mitosis. Notably, we also found that GTPase Ran is also involved in the regulation of RanBP2-importin ?1 interaction. Overall, our results suggest that mitotic arrest and the following cell death were caused by depletion of RanBP2. Our findings point to a crucial role for RanBP2 in proper mitotic progression and faithful chromosomal segregation. PMID:24113188

  3. 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

  4. 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.

  5. Dynein-like Mg2+-ATPase in mitotic spindles isolated from sea urchin embryos (Strongylocentrotus droebachiensis).

    PubMed

    Pratt, M M; Otter, T; Salmon, E D

    1980-09-01

    Two distinctly different ATPases have been reported to be endogenous to the mitotic apparatus: a Mg2+-ATPase resembling axonemal dynein, and a Ca2+-ATPase postulated to be bound in membranes. To examine the nature of the Mg2+-ATPase, we isolated membrane-free mitotic spindles from Stronglylocentrotus droebachiensis embryos by rapidly lysing these in a calcium-chelating, low-ionic-strength buffer (5 mM EGTA, 0.5 mM MgCl2, 10 mM PIPES, pH 6.8) that contained 1% Nonidet P-40. The fibrous isolated mitotic spindles closely resembled spindles in living cells, both in general morphology and in birefringence. In electron micrographs, the spindles were composed primarily of microtubules, free from membranes and highly extracted of intermicrotubular cytoplasmic ground substance. As analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), the pelleted spindles contain 18% tubulin, variable amounts of actin (2-8%), and an unidentified protein of 55 kdaltons in a constant weight ratio to tubulin (1:2.5). The isolated spindles also contained two polypeptides, larger than 300 kdaltons, that comigrated with egg dynein polypeptides, and ATPase activity (0.02 mumol Pi/mg . min) that closely resembled both flagellar and egg dynein. The spindle Mg2+-ATPase showed a ratio of Ca2+-/Mg2+-ATPase = 0.85, had minimal activity in KCl and EDTA, and cleaved GTP at 35% of the rate of ATP. The Mg2+-ATPase was insensitive to ouabain or oligomycin. The spindle Mg2+-ATPase was inhibited by sodium vanadate but, like egg dynein, was less sensitive to vanadate than flagellar dynein. The spindle Mg2+-ATPase does not resemble the mitotic Ca2+-ATPase described by others. We propose that the spindle Mg2+-ATPase is egg dynein. Bound carbohydrate on the two high-molecular-weight polypeptides of both egg dynein and the spindle enzyme suggest that these proteins may normally associate with membranes in the living cell. PMID:6447705

  6. Relationships among Repetitive Behaviors, Sensory Features, and Executive Functions in High Functioning Autism.

    PubMed

    Boyd, Brian A; McBee, Matthew; Holtzclaw, Tia; Baranek, Grace T; Bodfish, James W

    2009-10-01

    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 explained any relationship between the variables. Particular types of repetitive behavior (i.e., stereotypy and compulsions) were related to sensory features in autism; however, executive deficits were only correlated with repetitive behavior. This finding suggests that executive dysfunction is not the shared neurocognitive mechanism that accounts for the relationship between restricted, repetitive behaviors and aberrant sensory features in HFA. Group status, younger chronological age, presence of sensory processing issues, and difficulties with behavior regulation predicted the presence of repetitive behaviors in the HFA group. PMID:21475640

  7. High-speed object matching and localization using gradient orientation features

    NASA Astrophysics Data System (ADS)

    Xu, Xinyu; van Beek, Peter; Feng, Xiaofan

    2013-12-01

    In many robotics and automation applications, it is often required to detect a given object and determine its pose (position and orientation) from input images with high speed, high robustness to photometric changes, and high pose accuracy. We propose a new object matching method that improves efficiency over existing approaches by decomposing orientation and position estimation into two cascade steps. In the first step, an initial position and orientation is found by matching with Histogram of Oriented Gradients (HOG), reducing orientation search from 2D template matching to 1D correlation matching. In the second step, a more precise orientation and position is computed by matching based on Dominant Orientation Template (DOT), using robust edge orientation features. The cascade combination of the HOG and DOT feature for high-speed and robust object matching is the key novelty of the proposed method. Experimental evaluation was performed with real-world single-object and multi-object inspection datasets, using software implementations on an Atom CPU platform. Our results show that the proposed method achieves significant speed improvement compared to an already accelerated template matching method at comparable accuracy performance.

  8. 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

  9. 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.

  10. Training high dimension ternary features with GA in boosting cascade detector for object detection

    Microsoft Academic Search

    Qian Chen; Kazuyuki Masada; Haiyuan Wu; Toshikazu Wada

    2008-01-01

    Viola et al. have introduced a fast object detection scheme based on a boosted cascade of haar-like features. In this paper, we introduce a novel ternary feature that enriches the diversity and the flexibility significantly over haar-like features. We also introduce a new genetic algorithm (GA) based method for training effective ternary features through iterations of feature generation and selection.

  11. Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism

    Microsoft Academic Search

    Robert V. Skibbens; Victoria Petrie Skeen; E. D. Salmon

    1993-01-01

    Most models of mitotic congression and segregation assume that only poleward pulling forces occur at kinetochores. However, there are reports for several different cell types that both mono-oriented and bi-oriented chromosomes oscillate toward and away from the pole throughout mitosis. We used new methods of high resolution video microscopy and computer-assisted tracking techniques to measure the positions over time of

  12. The Effect of Three Agricultural Chemicals on Mitotic Division and Total Seed Protein Banding Profiles of Alfalfa (Vicia faba)

    Microsoft Academic Search

    MEKKI LAILA

    Treatments of alfalfa (Vicia faba L.) seeds with gibberellic acid (GA3), fertilizer, potassium oxide (K2O) and the auxin inhibitor N-meta-tolyl-phathalamic acid (Tomaset) showed a decrease in mitotic index and increased the percentage of the chromosomal abnormalities. The harmful effect was high with the use of tomaset, moderate with K2O and low in plants treated with GA3. SDS-PAGE studies revealed qualitative

  13. 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.

  14. Chromosome Condensation in Xenopus Mitotic Extracts Without Histone H1

    Microsoft Academic Search

    Keita Ohsumi; Chiaki Katagiri; Takeo Kishimoto

    1993-01-01

    The contribution of histone H1 to mitotic chromosome condensation was examined with the use of a cell-free extract from Xenopus eggs, which transforms condensed sperm nuclei into metaphase chromosomes. When H1 was removed from the extract, the resultant metaphase chromosomes were indistinguishable from those formed in complete extract. Nucleosomal spacing was the same for both. Thus, H1 is not required

  15. Mitotic clonal expansion: A synchronous process required for adipogenesis

    Microsoft Academic Search

    Qi-Qun Tang; Tamara C. Otto

    2002-01-01

    When induced to differentiate, growth-arrested 3T3-L1 preadipocytes synchronously reenter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The preadipocytes traverse the G1\\/S checkpoint synchronously as evidenced by the expression\\/activation of cdk2-cyclin-E\\/A, turnover of p27\\/kip1, hyperphosphorylation of Rb, translocation of cyclin D1 from nuclei to cytoplasm and GSK-3 from cytoplasm

  16. 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.

  17. Timing and Checkpoints in the Regulation of Mitotic Progression

    Microsoft Academic Search

    Patrick Meraldi; Viji M. Draviam; Peter K. Sorger

    2004-01-01

    Accurate chromosome segregation relies on the precise regulation of mitotic progression. Regulation involves control over the timing of mitosis and a spindle assembly checkpoint that links anaphase onset to the completion of chromosome-microtubule attachment. In this paper, we combine live-cell imaging of HeLa cells and protein depletion by RNA interference to examine the functions of the Mad, Bub, and kinetochore

  18. High-Velocity Features in the Spectra of Type-Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Silverman, Jeffrey M.; Marion, Howie; Vinko, Jozsef; Mulligan, Brian W.; Wheeler, J. Craig; Filippenko, Alexei V.

    2015-01-01

    Spectra of Type-Ia supernovae (SNe Ia) obtained before maximum brightness sometimes show high-velocity features (HVFs). They are most often seen in Si II and Ca II and in the most obvious cases appear as a second, separate absorption feature at ~7000-10000 km/s higher expansion velocity than the more normal photospheric-velocity features (PVFs). We have investigated how often HVFs occur, at what epochs, and how they evolve with time using a large sample of low-resolution, optical and NIR spectra of nearby SNe Ia. Our ongoing study indicates that HVFs are quite common in SNe Ia spectra obtained prior to 5 days before maximum brightness. Correlations between photometric observables and the relative line strengths and expansion velocities of both HVFs and PVFs are currently being sought and some intriguing results have already been found and will be discussed. Various explanations for the existence and behavior of the HVFs are being considered, with possibilities including density enhancements in the outer portion of the SN ejecta and low levels of interaction with circumstellar material.

  19. Fully automatic 2D to 3D conversion with aid of high-level image features

    NASA Astrophysics Data System (ADS)

    Appia, Vikram; Batur, Umit

    2014-03-01

    With the recent advent in 3D display technology, there is an increasing need for conversion of existing 2D content into rendered 3D views. We propose a fully automatic 2D to 3D conversion algorithm that assigns relative depth values to the various objects in a given 2D image/scene and generates two different views (stereo pair) using a Depth Image Based Rendering (DIBR) algorithm for 3D displays. The algorithm described in this paper creates a scene model for each image based on certain low-level features like texture, gradient and pixel location and estimates a pseudo depth map. Since the capture environment is unknown, using low-level features alone creates inaccuracies in the depth map. Using such flawed depth map for 3D rendering will result in various artifacts, causing an unpleasant viewing experience. The proposed algorithm also uses certain high-level image features to overcome these imperfections and generates an enhanced depth map for improved viewing experience. Finally, we show several 3D results generated with our algorithm in the results section.

  20. 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

  1. 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.

  2. 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.

  3. Cytoplasmic dynein plays a role in mammalian mitotic spindle formation

    PubMed Central

    1993-01-01

    The formation and functioning of a mitotic spindle depends not only on the assembly/disassembly of microtubules but also on the action of motor enzymes. Cytoplasmic dynein has been localized to spindles, but whether or how it functions in mitotic processes is not yet known. We have cloned and expressed DNA fragments that encode the putative ATP- hydrolytic sites of the cytoplasmic dynein heavy chain from HeLa cells and from Dictyostelium. Monospecific antibodies have been raised to the resulting polypeptides, and these inhibit dynein motor activity in vitro. Their injection into mitotic mammalian cells blocks the formation of spindles in prophase or during recovery from nocodazole treatment at later stages of mitosis. Cells become arrested with unseparated centrosomes and form monopolar spindles. The injected antibodies have no detectable effect on chromosome attachment to a bipolar spindle or on motions during anaphase. These data suggest that cytoplasmic dynein plays a unique and important role in the initial events of bipolar spindle formation, while any later roles that it may play are redundant. Possible mechanisms of dynein's involvement in mitosis are discussed. PMID:8227145

  4. APC/C-Cdh1-dependent anaphase and telophase progression during mitotic slippage

    PubMed Central

    2012-01-01

    Background The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons. Results Here we describe mitotic slippage in yeast bub2? mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments. Conclusions The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans. PMID:22321970

  5. 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

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

    PubMed

    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

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

    PubMed

    O'Regan, Laura; Sampson, Josephina; Richards, Mark W; Knebel, Axel; Roth, Daniel; Hood, Fiona E; Straube, Anne; Royle, Stephen J; Bayliss, Richard; Fry, Andrew M

    2015-05-11

    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-fiber-stabilizing 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 MT-kinetochore 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-TOG-TACC3 complex. PMID:25940345

  8. 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.

  9. The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C.

    PubMed

    Izawa, Daisuke; Pines, Jonathon

    2015-01-29

    The spindle assembly checkpoint (SAC) maintains genomic stability by delaying chromosome segregation until the last chromosome has attached to the mitotic spindle. The SAC prevents the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase from recognizing cyclin B and securin by catalysing the incorporation of the APC/C co-activator, CDC20, into a complex called the mitotic checkpoint complex (MCC). The SAC works through unattached kinetochores generating a diffusible 'wait anaphase' signal that inhibits the APC/C in the cytoplasm, but the nature of this signal remains a key unsolved problem. Moreover, the SAC and the APC/C are highly responsive to each other: the APC/C quickly targets cyclin B and securin once all the chromosomes attach in metaphase, but is rapidly inhibited should kinetochore attachment be perturbed. How this is achieved is also unknown. Here, we show that the MCC can inhibit a second CDC20 that has already bound and activated the APC/C. We show how the MCC inhibits active APC/C and that this is essential for the SAC. Moreover, this mechanism can prevent anaphase in the absence of kinetochore signalling. Thus, we propose that the diffusible 'wait anaphase' signal could be the MCC itself, and explain how reactivating the SAC can rapidly inhibit active APC/C. PMID:25383541

  10. Regulation of mitotic spindle disassembly by an environmental stress-sensing pathway in budding yeast.

    PubMed

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

    2014-11-01

    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

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

    SciTech Connect

    Levakhina, Y. M. [Institute of Medical Engineering, University of Luebeck, Luebeck 23562, Germany and Graduate School for Computing in Medicine and Life Sciences, Luebeck 23562 (Germany); Mueller, J.; Buzug, T. M. [Institute of Medical Engineering, University of Luebeck, Luebeck 23562 (Germany); Duschka, R. L.; Vogt, F.; Barkhausen, J. [Clinic for Radiology, University Clinics Schleswig-Holstein, Luebeck 23562 (Germany)

    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.

  12. 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.

  13. 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.

  14. Study of some features of the lethal effect of high-intensity 266 nm ultraviolet radiation on yeast cells

    NASA Astrophysics Data System (ADS)

    Burchuladze, T. G.; Valeva, S. A.; Fra?kin, G. Ya; Rubin, L. B.

    1981-12-01

    A study is made of some features of the inactivation, photoreactivation, and photoprotection of yeast cells exposed to high-intensity 266 nm ultraviolet laser radiation. A possible mechanism responsible for laser-induced lethal lesions is discussed.

  15. Extent of apoptosis in ovarian serous carcinoma: relation to mitotic and proliferative indices, p53 expression, and survival.

    PubMed Central

    McMenamin, M E; O'Neill, A J; Gaffney, E F

    1997-01-01

    AIMS: To assess the extent of apoptosis in ovarian serous carcinoma and to examine possible relations between apoptosis, cell proliferation, p53 overexpression, and patient survival. METHODS: Apoptotic and mitotic indices were obtained by examining haematoxylin and eosin stained sections from 30 patients with ovarian serous carcinoma. Apoptosis was also evaluated semiquantitatively by in situ end labelling of fragmented DNA. Expression of p53 and determination of Ki-67 labelling indices were based on immunohistochemical staining. Clinical details were obtained from patients' clinical records. For statistical analysis, Fisher's exact test, parametric (Pearson) linear correlations, and the Kaplan-Meier method were used. RESULTS: The mean apoptotic index was 1.3% (range 0.02-3.9%), the mean mitotic index was 0.4% (range 0.02-1.1%), and the mean Ki-67 labelling index was 16% (range 4-32%). There were significant correlations between the apoptotic and mitotic indices (p < 0.0205) and between the mitotic and Ki-67 labelling indices (p < 0.024). There was a significant correlation between a high apoptotic index and poor prognosis (p < 0.02). p53 was overexpressed in 16 cases but the extent of apoptosis and outcome were both independent of p53 status. CONCLUSIONS: These results suggest that regulation of apoptosis is an integral component of tumour cell kinetics in ovarian serous carcinoma, and that increased apoptosis is indicative of aggressive tumour growth. p53 expression did not correlate with altered apoptosis, but the possibility of an attenuated apoptotic response to subsequent DNA damage by anticancer agents is not excluded. Images PMID:9497913

  16. COP-coated vesicles are involved in the mitotic fragmentation of Golgi stacks in a cell-free system

    PubMed Central

    1994-01-01

    Rat liver Golgi stacks fragmented when incubated with mitotic but not interphase cytosol in a process dependent on time, temperature, energy (added in the form of ATP) and cdc2 kinase. The cross-sectional length of Golgi stacks fell in the presence of mitotic cytosol by approximately 50% over 30 min without a corresponding decrease in the number of cisternae in the stack. The loss of membrane from stacked and single cisternae occurred with a half-time of approximately 20 min, and was matched by the appearance of both small (50-100 nm in diameter) and large (100-200 nm in diameter) vesicular profiles. Small vesicular profiles constituted more than 50% of the total membrane after 60 min of incubation and they were shown to be vesicles or very short tubules by serial sectioning. In the presence of GTP gamma S all of the small vesicles were COP-coated and both the extent and the rate at which they formed were sufficient to account for the production of small vesicles during mitotic incubation. The involvement of the COP-mediated budding mechanism was confirmed by immunodepletion of one of the subunits of COP coats (the coatomer) from mitotic cytosol. Vesicles were no longer formed but highly fenestrated networks appeared, an effect reversed by the readdition of purified coatomer. Together these experiments provide strong support for our hypothesis that the observed vesiculation of the Golgi apparatus during mitosis in animal cells is caused by continued budding of COP-coated transport vesicles but an inhibition of their fusion with their target membranes. PMID:8163545

  17. 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 (?) for detected jet features under the CMB jet emission model. There is no discernible trend of ? 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

  18. Bridging low-level features and high-level semantics via fMRI brain imaging for video classification

    Microsoft Academic Search

    Xintao Hu; Fan Deng; Kaiming Li; Tuo Zhang; Hanbo Chen; Xi Jiang; Jinglei Lv; Dajiang Zhu; Carlos Faraco; Degang Zhang; Arsham Mesbah; Junwei Han; Xiansheng Hua; Li Xie; Stephen Miller; Lei Guo; Tianming Liu

    2010-01-01

    The multimedia content analysis community has made significant effort to bridge the gap between low-level features and high-level semantics perceived by human cognitive systems such as real-world objects and concepts. In the two fields of multimedia analysis and brain imaging, both topics of low-level features and high level semantics are extensively studied. For instance, in the multimedia analysis field, many

  19. Design features of a high-intensity, cesium-sputter/plasma-sputter negative ion sourcea)

    NASA Astrophysics Data System (ADS)

    Alton, G. D.; Mills, G. D.; Dellwo, J.

    1994-06-01

    A versatile, high-intensity, negative ion source has been designed and is now under construction which can be operated in either the cesium-sputter or plasma-sputter mode. The cesium-sputter mode can be effected by installation of a newly designed conical-geometry cesium-surface ionizer; for operation in the plasma-sputter mode, the surface ionizer is removed and either a hot filament or rf antenna plasma-discharge igniter is installed. A multicusp magnetic field is specifically provided confining the plasma in the radial direction when the plasma-sputter mode is selected. This arrangement allows comparison of the two modes of operation. Brief descriptions of the design features, ion optics, and anticipated performances of the two source geometries will be presented in this report.

  20. Leakage Reduction Effect by Multiple Cracking Feature of High Performance Fiber Reinforced Cement Composite

    NASA Astrophysics Data System (ADS)

    Ueno, Kazuhiro; Natsuka, Isamu; Ishii, Masayuki

    In a kind of concrete canal, repair materials are applied for recovery of the deteriorated functions. However, due to the re-cracking of the repair material caused by the fluctuations of the crack width, there is a great possibility that the functional deterioration reoccurs after the repair. In this research, High Performance Fiber Reinforced Cement Composite (HPFRCC), which has multiple cracking feature, was evaluated as a repair material to prevent the functional deterioration after the repair. HPFRCC and mortar specimens were cracked and examined by permeability test. As a result, it was clarified that the leakage from the HPFRCC specimen was very little compared with the leakage from the mortar specimen. Moreover, it was confirmed that the leakage from the narrow cracks were gradually decreased.

  1. A Compact Circumstellar Shell as the Source of High--velocity Features in SN 2011fe

    E-print Network

    Mulligan, Brian W

    2015-01-01

    High--velocity features (HVF), especially of Ca II, are frequently seen in Type Ia supernovae observed prior to B-band maximum (Bmax). These HVF start at more than 25,000 km/s in the days after first light, and slow to about 18,000 km/s near Bmax. To recreate the Ca II near-infrared triplet (CaNIR) HVF in SN 2011fe, we consider the interaction between a Type Ia supernova and a compact circumstellar shell, employing a hydrodynamic 1-D simulation using FLASH. We generate synthetic spectra from the hydrodynamic results using syn++. We show that the CaNIR HVF and its velocity evolution is better explained by a supernova model interacting with a shell than a model without a shell, and briefly discuss the implications for progenitor models.

  2. 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.

  3. High Temperature Gas-Cooled Reactors: Design Features, Potential and Challenges

    SciTech Connect

    Methnani, Mabrouk [International Atomic Energy Agency, Wagramerstrasse 5, P.O.Box 100, A-1400 Vienna (Austria)

    2006-07-01

    Over a period spanning more than half-a century, the High-Temperature Gas-cooled Reactor (HTGR) design has evolved from early experimental prototypes with single-coating fuel to more recent modular designs featuring TRISO fuel and a Brayton cycle gas turbine design, promising enhanced safety and improved economics. In this paper, the current status of the technology is reviewed, starting with a brief introduction and a descriptive history of the evolving design. This is followed by an overview of the special fuel and core design aspects, including core physics, thermal-hydraulics, reactivity control and fuelling schemes. An overview of safety performance is also presented, followed by an outline of the various power conversion unit layouts, the Brayton cycle main characteristics and the potential process heat applications of this particular design. A brief overview of the challenges facing HTGR designs and the status of research and development work is also presented. (authors)

  4. Centrosomes and the art of mitotic spindle maintenance.

    PubMed

    Hinchcliffe, Edward H

    2014-01-01

    The assembly of a bipolar spindle lies at the heart of mitotic chromosome segregation. In animal somatic cells, the process of spindle assembly involves multiple complex interactions between various cellular compartments, including an emerging antiparallel microtubule network, microtubule-associated motor proteins and spindle assembly factors, the cell's cortex, and the chromosomes themselves. The result is a dynamic structure capable of aligning pairs of sister chromatids, sensing chromosome misalignment, and generating force to segregate the replicated genome into two daughters. Because the centrosome lies at the center of the array of microtubule minus-ends, and the essential one-to-two duplication of the centrosome prior to mitosis is linked to cell cycle progression, this organelle has long been implicated as a device to generate spindle bipolarity. However, this classic model for spindle assembly is challenged by observations and experimental manipulations demonstrating that acentrosomal cells can and do form bipolar spindles, both mitotic and meiotic. Indeed, recent comprehensive proteomic analysis of centrosome-dependent versus independent mitotic spindle assembly mechanisms reveals a large, common set of genes required for both processes, with very few genes needed to differentiate between the two. While these studies cast doubt on an absolute role for the centrosome in establishing spindle polarity, it is clear that having too few or too many centrosomes results in abnormal chromosome segregation and aneuploidy. Here we review the case both for and against the role of the centrioles and centrosomes in ensuring proper assembly of a bipolar spindle, an essential element in the maintenance of genomic stability. PMID:25376493

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. High-frequency oscillations detected in epileptic networks using swarmed neural-network features.

    PubMed

    Firpi, Hiram; Smart, Otis; Worrell, Greg; Marsh, Eric; Dlugos, Dennis; Litt, Brian

    2007-09-01

    Localizing epileptic networks is a central challenge in guiding epilepsy surgery, deploying antiepileptic devices, and elucidating mechanisms underlying seizure generation. Recent work from our group and others suggests that high-frequency epileptic oscillations (HFEOs) arise from brain regions constituting epileptic networks, and may be important to seizure generation. HFEOs are brief 50-500 Hz pathologic events measured in intracranial field and unit recordings in patients with refractory epilepsy. They are challenging to detect due to low signal to noise ratio, and because they occur in multiple channels with great frequency. Their morphology is also variable and changes with distance from intracranial electrode contacts, which are sparsely placed for patient safety. Thus reliable, automated methods to detect HFEOs are required to localize and track seizure generation in epileptic networks. We present a novel method for mapping the temporal evolution of these oscillations in human epileptic networks. The technique combines a particle swarm optimization algorithm with a neural network to create features that robustly detect and track HFEOs in human intracranial EEG (IEEG) recordings. We demonstrate the algorithm's performance on IEEG data from six patients, one pediatric and five adult, and compare it to an existing method for detecting high-frequency oscillations. PMID:17541826

  11. Correlation between High Endothelial Vessels and Histopathological Features of Different Pigmented Lesions

    PubMed Central

    AVRAM, GABRIELA; MIXICH, F.; IOANA, M.; PATRASCU, V; MONTEAGUDO, C.

    2014-01-01

    Purpose: Tumor infiltrating lymphocytes are playing an important role in cutaneous melanoma being a strong prognostic parameter. Our goal was to study the presence of high endothelial vessels in correlation with the histopathological features in different pigmented skin lesions. Material and methods: our study group included 60 patients (20 cases with dysplastic nevi, 20 thin melanoma and 20 thick melanoma). For each patient we noted epidemiological and clinico-pathological characteristics including: age, gender, anatomic sites, regression, Breslow thickness, mitoses, Clark level and lymphocytic infiltration. Using immunohistochemistry staining we identified the presence of high endothelial vessels in our groups. Results: the most common localization of primary melanoma was trunk 57,5%, followed by extremities 35% and head 7,5%. We found positive MECA-79 vessels in 67% of primary melanoma samples and in 30% of dysplastic nevi. Lymphocytic infiltration was present in 80% samples of dysplastic nevi and 75% of primary melanomas. Using Kruskal Wallis non-parametric test we found a positive association between MECA-79+ vessels and different anatomic sites (p<0,01). We have also found a significant correlation between MECA-79+ vessels and the presence of regression in melanoma samples. In conclusion a better understanding of tumor microenvironment and mechanisms involved in anti-tumor response might play an important role in development of future melanoma therapeutic strategies. PMID:24791201

  12. High-throughput Biological Cell Classification Featuring Real-time Optical Data Compression

    E-print Network

    Jalali, Bahram; Chen, Claire L

    2015-01-01

    High throughput real-time instruments are needed to acquire large data sets for detection and classification of rare events. Enabled by the photonic time stretch digitizer, a new class of instruments with record throughputs have led to the discovery of optical rogue waves [1], detection of rare cancer cells [2], and the highest analog-to-digital conversion performance ever achieved [3]. Featuring continuous operation at 100 million frames per second and shutter speed of less than a nanosecond, the time stretch camera is ideally suited for screening of blood and other biological samples. It has enabled detection of breast cancer cells in blood with record, one-in-a-million, sensitivity [2]. Owing to their high real-time throughput, instruments produce a torrent of data - equivalent to several 4K movies per second - that overwhelm data acquisition, storage, and processing operations. This predicament calls for technologies that compress images in optical domain and in real-time. An example of this, based on war...

  13. 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

  14. Inhibition of mitotic-specific histone phophorylation by sodium arsenite

    SciTech Connect

    Cobo, J.M. [Universidad de Alcala de Henares, Madrid (Spain); Valdez, J.G.; Gurley, L.R. [Los Alamos National Lab., NM (United States)

    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.

  15. Integrin-Linked Kinase Regulates Interphase and Mitotic Microtubule Dynamics

    PubMed Central

    Lim, Simin; Kawamura, Eiko; Fielding, Andrew B.; Maydan, Mykola; Dedhar, Shoukat

    2013-01-01

    Integrin-linked kinase (ILK) localizes to both focal adhesions and centrosomes in distinct multiprotein complexes. Its dual function as a kinase and scaffolding protein has been well characterized at focal adhesions, where it regulates integrin-mediated cell adhesion, spreading, migration and signaling. At the centrosomes, ILK regulates mitotic spindle organization and centrosome clustering. Our previous study showed various spindle defects after ILK knockdown or inhibition that suggested alteration in microtubule dynamics. Since ILK expression is frequently elevated in many cancer types, we investigated the effects of ILK overexpression on microtubule dynamics. We show here that overexpressing ILK in HeLa cells was associated with a shorter duration of mitosis and decreased sensitivity to paclitaxel, a chemotherapeutic agent that suppresses microtubule dynamics. Measurement of interphase microtubule dynamics revealed that ILK overexpression favored microtubule depolymerization, suggesting that microtubule destabilization could be the mechanism behind the decreased sensitivity to paclitaxel, which is known to stabilize microtubules. Conversely, the use of a small molecule inhibitor selective against ILK, QLT-0267, resulted in suppressed microtubule dynamics, demonstrating a new mechanism of action for this compound. We further show that treatment of HeLa cells with QLT-0267 resulted in higher inter-centromere tension in aligned chromosomes during mitosis, slower microtubule regrowth after cold depolymerization and the presence of a more stable population of spindle microtubules. These results demonstrate that ILK regulates microtubule dynamics in both interphase and mitotic cells. PMID:23349730

  16. Endogenous localizome identifies 43 mitotic kinesins in a plant cell.

    PubMed

    Miki, Tomohiro; Naito, Haruko; Nishina, Momoko; Goshima, Gohta

    2014-03-18

    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

  17. 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

  18. Making microtubules and mitotic spindles in cells without functional centrosomes.

    PubMed

    Mahoney, Nicole M; Goshima, Gohta; Douglass, Adam D; Vale, Ronald D

    2006-03-21

    Centrosomes are considered to be the major sites of microtubule nucleation in mitotic cells (reviewed in ), yet mitotic spindles can still form after laser ablation or disruption of centrosome function . Although kinetochores have been shown to nucleate microtubules, mechanisms for acentrosomal spindle formation remain unclear. Here, we performed live-cell microscopy of GFP-tubulin to examine spindle formation in Drosophila S2 cells after RNAi depletion of either gamma-tubulin, a microtubule nucleating protein, or centrosomin, a protein that recruits gamma-tubulin to the centrosome. In these RNAi-treated cells, we show that poorly focused bipolar spindles form through the self-organization of microtubules nucleated from chromosomes (a process involving gamma-tubulin), as well as from other potential sites, and through the incorporation of microtubules from the preceding interphase network. By tracking EB1-GFP (a microtubule-plus-end binding protein) in acentrosomal spindles, we also demonstrate that the spindle itself represents a source of new microtubule formation, as suggested by observations of numerous microtubule plus ends growing from acentrosomal poles toward the metaphase plate. We propose that the bipolar spindle propagates its own architecture by stimulating microtubule growth, thereby augmenting the well-described microtubule nucleation pathways that take place at centrosomes and chromosomes. PMID:16546079

  19. Universal features in the photoemission spectroscopy of high-temperature superconductors

    PubMed Central

    Zhao, Junjing; Chatterjee, Utpal; Ai, Dingfei; Hinks, David G.; Zheng, Hong; Gu, G. D.; Castellan, John-Paul; Rosenkranz, Stephan; Claus, Helmut; Norman, Michael R.; Randeria, Mohit; Campuzano, Juan Carlos

    2013-01-01

    The energy gap for electronic excitations is one of the most important characteristics of the superconducting state, as it directly reflects the pairing of electrons. In the copper–oxide high-temperature superconductors (HTSCs), a strongly anisotropic energy gap, which vanishes along high-symmetry directions, is a clear manifestation of the d-wave symmetry of the pairing. There is, however, a dramatic change in the form of the gap anisotropy with reduced carrier concentration (underdoping). Although the vanishing of the gap along the diagonal to the square Cu–O bond directions is robust, the doping dependence of the large gap along the Cu–O directions suggests that its origin might be different from pairing. It is thus tempting to associate the large gap with a second-order parameter distinct from superconductivity. We use angle-resolved photoemission spectroscopy to show that the two-gap behavior and the destruction of well-defined electronic excitations are not universal features of HTSCs, and depend sensitively on how the underdoped materials are prepared. Depending on cation substitution, underdoped samples either show two-gap behavior or not. In contrast, many other characteristics of HTSCs, such as the dome-like dependence of on doping, long-lived excitations along the diagonals to the Cu–O bonds, and an energy gap at the Brillouin zone boundary that decreases monotonically with doping while persisting above (the pseudogap), are present in all samples, irrespective of whether they exhibit two-gap behavior or not. Our results imply that universal aspects of high- superconductivity are relatively insensitive to differences in the electronic states along the Cu–O bond directions. PMID:24101464

  20. MITOTIC ACTIVITY OF IMMUNOLOGICALLY COMPETENT LYMPHOID CELLS TRANSFERRED INTO X-IRRADIATED RECIPIENTS

    Microsoft Academic Search

    A. Zlotnick; J. J. Vazquez; F. J. Dixon

    1962-01-01

    A study was made to ascertain whether mitotic activity in cell transfer ; sites could be readily observed by colchicineinduced mitotic arrest, and, if so, ; whether the rate of division would be sufficient to indicate that antibody-; containing cells could develop from a relatively small number of precursors in a ; manner similar to that in the intact animal.

  1. Global Analysis of Cdc14 Phosphatase Reveals Diverse Roles in Mitotic Processes*S

    E-print Network

    Chait, Brian T.

    Global Analysis of Cdc14 Phosphatase Reveals Diverse Roles in Mitotic Processes*S Received and § Yale University, New Haven, Connecticut 06511 Cdc14 phosphatase regulates multiple events during an- aphase and is essential for mitotic exit in budding yeast. Cdc14 is regulated in both a spatial

  2. Autoreducibility, Mitoticity, and Immunity Christian Glaer # , Mitsunori Ogihara + , A. Pavan # , Alan L. Selman , Liyu Zhang

    E-print Network

    Selman, Alan

    Autoreducibility, Mitoticity, and Immunity Christian Glaßer # , Mitsunori Ogihara + , A. Pavan­complete sets are not 2 n(1+#) ­immune. These results solve several of the open questions raised by Buhrman sets in the class. Here we focus attention primarily on autoreducibility, mitoticity, and immunity

  3. Branching and Circular Features in High Dimensional Bei Wang, Brian Summa, Valerio Pascucci, and Mikael Vejdemo-Johansson

    E-print Network

    Utah, University of

    1 Branching and Circular Features in High Dimensional Data Bei Wang, Brian Summa, Valerio Pascucci Salt Lake City, UT 84112 USA May 30, 2011 Abstract: Large observations and simulations in scientific research give rise to high-dimensional data sets that present many challenges and opportunities in data

  4. Mitotic catenation is monitored and resolved by a PKC?-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 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

  5. Preparation of tomato meiotic pachytene and mitotic metaphase chromosomes suitable for fluorescence in situ hybridization (FISH).

    PubMed

    Zhong, X B; Hans de Jong, J; Zabel, P

    1996-01-01

    Fluorescence in situ hybridization (FISH) is an increasingly powerful tool with a variety of applications in both basic and applied research. With excellent genetic, cytogenetic and molecular maps available, the tomato genome provides a good model to benefit from the full potential of FISH. Tomato chromosomes at mitotic metaphase are small and not particularly suitable for high-resolution FISH. In contrast, chromosomes at meiotic pachytene are about 15 times longer, and easier to identify by their differences in chromosome arm lengths and chromomere pattern. We have developed a technique for preparing chromosomal spreads of young pollen mother cells at mid-prophase I which is suitable for FISH. In a first series of experiments, the hybridization patterns of three classes of repetitive DNA sequences were studied in single and multicolour FISH. PMID:8653264

  6. 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.

  7. The distribution of cytoplasmic microtubules throughout the cell cycle of the centric diatom Stephanopyxis turris: their role in nuclear migration and positioning the mitotic spindle during cytokinesis

    PubMed Central

    1986-01-01

    The cell cycle of the marine centric diatom Stephanopyxis turris consists of a series of spatially and temporally well-ordered events. We have used immunofluorescence microscopy to examine the role of cytoplasmic microtubules in these events. At interphase, microtubules radiate out from the microtubule-organizing center, forming a network around the nucleus and extending much of the length and breadth of the cell. As the cell enters mitosis, this network breaks down and a highly ordered mitotic spindle is formed. Peripheral microtubule bundles radiate out from each spindle pole and swing out and away from the central spindle during anaphase. Treatment of synchronized cells with 2.5 X 10(-8) M Nocodazole reversibly inhibited nuclear migration concurrent with the disappearance of the extensive cytoplasmic microtubule arrays associated with migrating nuclei. Microtubule arrays and mitotic spindles that reformed after the drug was washed out appeared normal. In contrast, cells treated with 5.0 X 10(-8) M Nocodazole were not able to complete nuclear migration after the drug was washed out and the mitotic spindles that formed were multipolar. Normal and multipolar spindles that were displaced toward one end of the cell by the drug treatment had no effect on the plane of division during cytokinesis. The cleavage furrow always bisected the cell regardless of the position of the mitotic spindle, resulting in binucleate/anucleate daughter cells. This suggests that in S. turris, unlike animal cells, the location of the plane of division is cortically determined before mitosis. PMID:3517004

  8. 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

  9. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly

    PubMed Central

    Huang, Hsiao-Chun; Shi, Jue; Orth, James D.; Mitchison, Timothy J.

    2009-01-01

    SUMMARY Current anti-mitotics work by perturbing spindle assembly, which activates the spindle assembly checkpoint, causes mitotic arrest, and triggers apoptosis. Cancer cells can resist such killing by premature exit, before cells initiate apoptosis, due to a weak checkpoint or rapid slippage. We reasoned blocking mitotic exit downstream of the checkpoint might circumvent this resistance. Using single-cell approaches, we showed that blocking mitotic exit by Cdc20 knockdown slowed cyclin B1 proteolysis, thus allowed more time for death initiation. Killing by Cdc20 knockdown did not require checkpoint activity, and can occur by intrinsic apoptosis, or an alternative death pathway when Bcl2 was over-expressed. We conclude targeting Cdc20, or otherwise blocking mitotic exit, may be a better cancer therapeutic strategy than perturbing spindle assembly. PMID:19800579

  10. 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.

  11. 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.

  12. Controlling the False Discovery Rate for Feature Selection in High-resolution NMR Spectra

    PubMed Central

    Kim, Seoung Bum; Chen, Victoria C. P.; Park, Youngja; Ziegler, Thomas R.; Jones, Dean P.

    2011-01-01

    Successful implementation of feature selection in nuclear magnetic resonance (NMR) spectra not only improves classification ability, but also simplifies the entire modeling process and, thus, reduces computational and analytical efforts. Principal component analysis (PCA) and partial least squares (PLS) have been widely used for feature selection in NMR spectra. However, extracting meaningful metabolite features from the reduced dimensions obtained through PCA or PLS is complicated because these reduced dimensions are linear combinations of a large number of the original features. In this paper, we propose a multiple testing procedure controlling false discovery rate (FDR) as an efficient method for feature selection in NMR spectra. The procedure clearly compensates for the limitation of PCA and PLS and identifies individual metabolite features necessary for classification. In addition, we present orthogonal signal correction to improve classification and visualization by removing unnecessary variations in NMR spectra. Our experimental results with real NMR spectra showed that classification models constructed with the features selected by our proposed procedure yielded smaller misclassification rates than those with all features. PMID:21461122

  13. Robustness of features for automatic target discrimination in high-resolution polarimetric SAR data

    NASA Astrophysics Data System (ADS)

    van den Broek, Albertus C.; Dekker, Rob J.; Steeghs, Phillippe

    2003-09-01

    We have studied the robustness of features against aspect variability for the purpose of target discrimination using polarimetric 35 Ghz ISAR data. Images at a resolution of 10 cm and 30 cm have been used for a complete aspect range of 360 degrees. The data covered four military targets: T72, ZSU23/4, T62, and BMP2. For the study we composed several feature vectors out of individual features extracted from the images. The features are divided into three categories: radiometric, geometric and polarimetric. We found that individual features show a strong variability as a function of aspect angle and cannot be used to discriminate between the targets irrespectively of the aspect angle. Using feature vectors and a maximum likelihood classifier reasonable discrimination (about 80%) between the four targets irrespective of the aspect angle was obtained at 10 cm resolution. At 30 cm resolution less significant discrimination (less than 70%) was found irrespective of the kind of feature vector used. In addition we investigated target discrimination per 30-degree aspect interval. In order to determine the aspect angle of targets we used a technique based on the Radon transformation, which gave an accuracy of about 5 degrees in aspect angle. We found that in this case good discrimination (more than 90%) was obtained at 10 cm resolution and reasonable discrimination (about 80%) at 30 cm resolution. The results are compared with analogous results from MSTAR data (30 cm resolution) of comparable targets.

  14. Molecular dissection of mitotic recombination in the yeast Saccharomyces cerevisiae.

    PubMed

    Aylon, Yael; Liefshitz, Batia; Bitan-Banin, Gili; Kupiec, Martin

    2003-02-01

    Recombination plays a central role in the repair of broken chromosomes in all eukaryotes. We carried out a systematic study of mitotic recombination. Using several assays, we established the chronological sequence of events necessary to repair a single double-strand break. Once a chromosome is broken, yeast cells become immediately committed to recombinational repair. Recombination is completed within an hour and exhibits two kinetic gaps. By using this kinetic framework we also characterized the role played by several proteins in the recombinational process. In the absence of Rad52, the broken chromosome ends, both 5' and 3', are rapidly degraded. This is not due to the inability to recombine, since the 3' single-stranded DNA ends are stable in a strain lacking donor sequences. Rad57 is required for two consecutive strand exchange reactions. Surprisingly, we found that the Srs2 helicase also plays an early positive role in the recombination process. PMID:12556499

  15. 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.

  16. Hormonal Control of Mitotic Development in Tobacco Protoplasts

    PubMed Central

    Meyer, Yves; Chartier, Yvette

    1981-01-01

    Two-dimensional separation of proteins newly synthesized by tobacco mesophyll protoplasts cultivated in vitro allows us to detect, reproducibly, 257 spots. The pattern is extremely stable throughout the three days of culture, the intensity of only 24 spots varying during this time. The absence of cytokinin (N6-benzyladenine) in the culture medium prohibits entry into S phase but does not modify the pattern, indicating that none of the observed proteins is specifically synthesized in S, G2, or M phases. The presence of 2,4-dichlorophenoxyacetic acid is necessary for the mitotic development of protoplasts. It induces the appearance of one protein, increases the level of another, and reduces that of eight others. All proteins sensitive to auxin belong to the group of proteins the levels of which vary during culture. Images PMID:16662091

  17. Model scenarios for switch-like mitotic transitions.

    PubMed

    Vinod, P K; Novak, Bela

    2015-03-12

    To facilitate rapid accumulation of Cdk1-phosphorylated substrate proteins, the Cdk1 counter-acting phosphatase, PP2A-B55 is inhibited during M phase by stoichiometric inhibitors (ENSA and Arpp19). These inhibitors are activated when phosphorylated by Cdk1-activated Greatwall-kinase. Recent experiments show that ENSA is dephosphorylated and inactivated by the PP2A-B55 itself, and acts as an unfair substrate inhibiting PP2A-B55 activity towards other Cdk1 substrates. Mathematical modelling shows that this mutual antagonism between the phosphatase and its inhibitor is insufficient to explain the switch-like characteristics of mitotic entry and exit. We show that the feedback regulation of Greatwall activating kinase and/or inactivating phosphatase can explain the abruptness of these cell cycle transitions. PMID:25683003

  18. 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

  19. Diverse Mitotic and Interphase Functions of Condensins in Drosophila

    PubMed Central

    Cobbe, Neville; Savvidou, Ellada; Heck, Margarete M. S.

    2006-01-01

    The condensin complex has been implicated in the higher-order organization of mitotic chromosomes in a host of model eukaryotes from yeasts to flies and vertebrates. Although chromosomes paradoxically appear to condense in condensin mutants, chromatids are not properly resolved, resulting in chromosome segregation defects during anaphase. We have examined the role of different condensin complex components in interphase chromatin function by examining the effects of various condensin mutations on position-effect variegation in Drosophila melanogaster. Surprisingly, most mutations affecting condensin proteins were often found to result in strong enhancement of variegation in contrast to what might be expected for proteins believed to compact the genome. This suggests either that the role of condensin proteins in interphase differs from their expected role in mitosis or that the way we envision condensin's activity needs to be modified to accommodate alternative possibilities. PMID:16272408

  20. 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

  1. High-Resolution Seismic Investigation of a Surface Collapse Feature at Weeks Island Salt Dome, Louisiana

    NASA Astrophysics Data System (ADS)

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

    2005-05-01

    Seismic imaging techniques delineated the subsurface expression of an active sinkhole above a former salt mine at Weeks Island, Louisiana, which was used at the time by the U.S. Department of Energy's Strategic Petroleum Reserve. (The Weeks Island salt dome is no longer part of the Reserve.) The sinkhole, which at the time of the survey was approximately 12 m wide and 11 m deep, is directly over the edge of the upper storage chamber and approximately 60 m above the top of the salt dome. Surface seismic reflections imaged a dramatic bowl-shaped depression in a 28-m-deep reflector spatially consistent with the sinkhole. Two reflections (28 m and 60 m) on multichannel VSP data represent the only velocity and/or density contrasts detected above the top of the salt dome. The 28-m reflector identified on both VSP and surface seismic reflection data is at a depth consistent with the piezometric surface. Considering the high measured permeability and relative geometric severity of the reflection geometry, it is questionable whether this drape in the 28-m reflection is consistent with the water table. Localized velocity variations could account for some of the apparent geometry. The 60-m salt reflection, evident on VSP, can be interpreted on selected processed surface seismic shot gathers, but is difficult to confidently and consistently identify on stacked sections. The sinkhole lies along a northeast-trending acoustic lineament, possibly related to or associated with salt dissolution. The acoustic expression of the sinkhole suggests a localized, predominantly vertical feature. No evidence was discovered to confidently ascertain the mechanism responsible for exposing the salt to unsaturated meteoric water.

  2. 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

  3. 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. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA (United States); Psaltis, Dimitrios, E-mail: swellons@cfa.harvard.edu [Astronomy Department, University of Arizona, 933 North Cherry Avenue, Tucson, AZ (United States)

    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.

  4. Paclitaxel sensitivity of breast cancer cells requires efficient mitotic arrest and disruption of Bcl-xL/Bak interaction.

    PubMed

    Flores, M Luz; Castilla, Carolina; Ávila, Rainiero; Ruiz-Borrego, Manuel; Sáez, Carmen; Japón, Miguel A

    2012-06-01

    Taxanes are being used for the treatment of breast cancer. However, cancer cells frequently develop resistance to these drugs with the subsequent recurrence of the tumor. MDA-MB-231 and T-47D breast cancer cell lines were used to assess the effect of paclitaxel treatment on apoptosis and cell cycle, the possible mechanisms of paclitaxel resistance as well as the enhancement of paclitaxel-induced apoptosis based on its combination with phenylethyl isothiocyanate (PEITC). T-47D cells undergo apoptosis in response to paclitaxel treatment. The induction of apoptosis was associated with a robust mitotic arrest and the disruption of Bcl-xL/Bak interaction. By contrary, MDA-MB-231 cells were insensitive to paclitaxel-induced apoptosis and this was associated with a high percentage of cells that slip out of paclitaxel-imposed mitotic arrest and also with the maintenance of Bcl-xL/Bak interaction. The sequential treatment of MDA-MB-231 cells with PEITC followed by paclitaxel inhibited the slippage induced by paclitaxel and increased the apoptosis induction achieved with any of the drugs alone. In breast cancer tissues, high Bcl-xL expression was correlated with a shorter time of disease-free survival in patients treated with a chemotherapeutic regimen that contains paclitaxel, in a statistically significant way. Thus, resistance to paclitaxel in MDA-MB-231 cells is related to the inability to disrupt the Bcl-xL/Bak interaction and increased slippage. In this context, the combination of a drug that induces a strong mitotic arrest, such as paclitaxel, with another that inhibits slippage, such as PEITC, translates into increased apoptotic induction. PMID:22076480

  5. Relative cataractogenic effects of X rays, fission-spectrum neutrons, and 56Fe particles: A comparison with mitotic effects

    SciTech Connect

    Riley, E.F.; Lindgren, A.L.; Andersen, A.L.; Miller, R.C.; Ainsworth, E.J. (Univ. of Iowa, Iowa City (USA))

    1991-03-01

    The eyes of Sprague-Dawley rats were irradiated with doses of 2.5-10 Gy 250-kVp X rays, 1.25-2.25 Gy fission-spectrum neutrons (approximately 0.85 MeV), or 0.1-2.0 Gy 600-MeV/A 56Fe particles. Lens opacifications were evaluated for 51-61 weeks following X and neutron irradiations and for 87 weeks following X and 56Fe-particle irradiations. Average stage of opacification was determined relative to time after irradiation, and the time required for 50% of the irradiated lenses to achieve various stages (T50) was determined as a function of radiation dose. Data from two experiments were combined in dose-effect curves as T50 experimental values taken as percentages of the respective T50 control values (T50-% control). Simple exponential curves best describe dose responsiveness for both high-LET radiations. For X rays, a shallow dose-effect relationship (shoulder) up to 4.5 Gy was followed at higher doses by a steeper exponential dose-effect relationship. As a consequence, RBE values for the high-LET radiations are dose dependent. Dose-effect curves for cataracts were compared to those for mitotic abnormalities observed when quiescent lens epithelial cells were stimulated mechanically to proliferate at various intervals after irradiation. Neutrons were about 1.6-1.8 times more effective than 56Fe particles for inducing both cataracts and mitotic abnormalities. For stage 1 and 2 cataracts, the X-ray Dq was 10-fold greater and the D0 was similar to those for mitotic abnormalities initially expressed after irradiation.

  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. 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.

  8. The 21 micron feature in the circumstellar envelopes around highly evolved stars

    NASA Astrophysics Data System (ADS)

    Zhang, Ke; Jiang, Bi-Wei; Li, Ai-Gen

    2006-03-01

    The origin of the so-called 21 micron feature which is prominent in the infrared (IR) spectra of some carbon-rich proto-planetary nebular (PPNe) has been a mystery since its first detection in 1989. So far, this feature has been detected in 12 PPNe (and possibly in two planetary nebulae associated with Wolf-Rayet central stars). This feature has a similar intrinsic spectral shape and peaks at the same wavelength (20.1 ?m) in all PPNe sources. These sources have quite uniform properties: they are mostly metal-poor, carbon-rich F and G supergiants with IR excesses and overabundant s-process elements. A large number of candidate carriers for this feature have been proposed in the past decade, including hydrogenated fullerenes, polycyclic aromatic hydrocarbon, hydrogenated amorphous carbon, diamonds, synthetic carbonaceous macromolecules, amides (especially urea), iron oxides (?-Fe2O3, Fe3O4, FeO), SiS2, titanium carbide nanoclusters, doped SiC, and SiC core-SiO2 mantle particles. But none of them has been widely accepted. In this paper we review the observational characteristics of this feature and the proposed candidate materials.

  9. 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.

  10. Incremental high pressure torsion as a novel severe plastic deformation process: Processing features and application to copper

    PubMed Central

    Hohenwarter, A.

    2015-01-01

    High pressure torsion is known as one of the most popular severe plastic deformation processes. However, it has certain size limitations, especially regarding the thickness of the processed samples. In this contribution incremental high pressure torsion is introduced as a novel severe plastic deformation process. This further development of conventional high pressure torsion is capable of delivering specimens having an extraordinarily high aspect-ratio of thickness to diameter. The features of this process combined with a case-study on a pure copper specimen with a deformed diameter of 50 mm and a thickness of 40 mm is presented. PMID:25892850

  11. 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 70°C 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

  12. 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.

  13. Localization of a high-speed mobile robot using global features

    Microsoft Academic Search

    SeungKeun Cho; TaeKyung Yang; MunGyu Choi; JangMyung Lee

    2009-01-01

    This paper proposes a new localization algorithm for a fast-moving mobile robot, which utilizes only one beacon and the global features of the differential-driving mobile robot. It takes a relatively long time to localize a mobile robot with active beacon sensors, since the distance to the beacon is measured by the freight time of the ultrasonic signal. When the mobile

  14. A novel high voltage bipolar technology featuring trench-isolated base

    Microsoft Academic Search

    H. Kim; J. Jin; C. Jeoun; Y. Choi; B. Kwon; S. Lim; K. Choi

    1994-01-01

    In this paper, we present a novel bipolar technology featuring the trench-isolated base. When employed for a conventional 2 ?m process, the trench isolation reduces both the surface leakage and current gain of the parasitic lateral pnp transistor by at least one order, which results in the improvement of the punchthrough-induced breakdown behavior by almost a factor of two. The

  15. 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…

  16. Image retrieval, classification and object recognition using local invariant features in high resolution remote sensing imagery

    E-print Network

    Yang, Yang

    2012-01-01

    Mahalanobis distance is equivalent to the Euclidean distance computed in a transformed feature spaceMahalanobis distance. This is true for using k-means clustering to construct the quantization space.space. This again differs from the findings of other researchers [26] who used the Mahalanobis

  17. High Accuracy Handwritten Chinese Character Recognition Using Quadratic Classifiers with Discriminative Feature Extraction

    E-print Network

    Paris-Sud XI, Université de

    hierarchical classification. Our experimental results on two large databases show that while the DFE improves proposed. Some important techniques, including directional feature extraction, non- linear normalization evaluated the effects of DFE and DLQDF on two large databases, ETL9B database and CASIA (Institute

  18. Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

    PubMed Central

    Akba?, H.; Yalcin, K.; Isi, H.; Tekes, S.; Atay, A.E.; Akkus, Z.; Budak, T.

    2012-01-01

    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

  19. Regulation and functions of Cdc14 in mitotic exit in Saccharomyces cerevisiae

    E-print Network

    Tomson, Brett N

    2009-01-01

    In order to ensure the accurate formation of two daughter cells from one parental cell, the series of events that comprise the mitotic cell division cycle must be carefully regulated. Much of this regulation affects the ...

  20. Physical lengths of meiotic and mitotic gene conversion tracts in Saccharomyces cerevisiae

    SciTech Connect

    Judd, S.R.; Petes, T.D.

    1988-03-01

    Physical lengths of gene conversion tracts for meiotic and mitotic conversions were examined, using the same diploid yeast strain in all experiments. This strain is heterozygous for a mutation in the URA3 gene as well as closely linked restriction site markers. In cells that had a gene conversion event at the URA3 locus, it was determined by Southern analysis which of the flanking heterozygous restriction sites had co-converted. It was found that mitotic conversion tracts were longer on the average than meiotic tracts. About half of the tracts generated by spontaneous mitotic gene conversion included heterozygous markers 4.2 kb apart; none of the meiotic conversions included these markers. Stimulation of mitotic gene conversion by ultraviolet light or methylmethanesulfonate had no obvious effect on the size or distribution of the tracts. Almost all conversion tracts were continuous.

  1. 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

  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. 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. (Merck)

    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.

  4. Identification of a Human Mitotic Checkpoint Gene: hsMAD2

    Microsoft Academic Search

    Yong Li; Robert Benezra

    1996-01-01

    In Saccharomyces cerevisiae, MAD2 is required for mitotic arrest if the spindle assembly is perturbed. The human homolog of MAD2 was isolated and shown to be a necessary component of the mitotic checkpoint in HeLa cells by antibody electroporation experiments. Human, or Homo sapiens, MAD2 (hsMAD2) was localized at the kinetochore after chromosome condensation but was no longer observed at

  5. XKCM1: A Xenopus Kinesin-Related Protein That Regulates Microtubule Dynamics during Mitotic Spindle Assembly

    Microsoft Academic Search

    Claire E Walczak; Timothy J Mitchison; Arshad Desai

    1996-01-01

    We isolated a cDNA clone encoding a kinesin-related protein, which we named XKCM1. Antibodies to XKCM1 stain mitotic centromeres and spindle poles. Immunodepletion and antibody addition experiments in an in vitro spindle assembly assay show that XKCM1 is required for both establishment and maintenance of mitotic spindles. The structures that form in the absence of XKCM1 contain abnormally long microtubules.

  6. The Structure of the Mitotic Spindle and Nucleolus during Mitosis in the Amebo-Flagellate Naegleria

    PubMed Central

    Walsh, Charles J.

    2012-01-01

    Mitosis in the amebo-flagellate Naegleria pringsheimi is acentrosomal and closed (the nuclear membrane does not break down). The large central nucleolus, which occupies about 20% of the nuclear volume, persists throughout the cell cycle. At mitosis, the nucleolus divides and moves to the poles in association with the chromosomes. The structure of the mitotic spindle and its relationship to the nucleolus are unknown. To identify the origin and structure of the mitotic spindle, its relationship to the nucleolus and to further understand the influence of persistent nucleoli on cellular division in acentriolar organisms like Naegleria, three-dimensional reconstructions of the mitotic spindle and nucleolus were carried out using confocal microscopy. Monoclonal antibodies against three different nucleolar regions and ?-tubulin were used to image the nucleolus and mitotic spindle. Microtubules were restricted to the nucleolus beginning with the earliest prophase spindle microtubules. Early spindle microtubules were seen as short rods on the surface of the nucleolus. Elongation of the spindle microtubules resulted in a rough cage of microtubules surrounding the nucleolus. At metaphase, the mitotic spindle formed a broad band completely embedded within the nucleolus. The nucleolus separated into two discreet masses connected by a dense band of microtubules as the spindle elongated. At telophase, the distal ends of the mitotic spindle were still completely embedded within the daughter nucleoli. Pixel by pixel comparison of tubulin and nucleolar protein fluorescence showed 70% or more of tubulin co-localized with nucleolar proteins by early prophase. These observations suggest a model in which specific nucleolar binding sites for microtubules allow mitotic spindle formation and attachment. The fact that a significant mass of nucleolar material precedes the chromosomes as the mitotic spindle elongates suggests that spindle elongation drives nucleolar division. PMID:22493714

  7. HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint

    Microsoft Academic Search

    S Kim; S-Y Park; H Yong; J K Famulski; S Chae; J-H Lee; C-M Kang; H Saya; G K Chan; H Cho

    2008-01-01

    Accurate chromosomal segregation is monitored by the mitotic checkpoint, and an increased rate of chromosomal missegregation leads to chromosomal instability (CIN). Here, we demonstrate that the HBV X protein (HBx) binds BubR1, a component of the mitotic checkpoint complex and co-localizes with BubR1 at the kinetochores. HBx binding to BubR1 attenuates the association between BubR1 and CDC20, an activator of

  8. Specific features of charge carrier scattering mechanisms in Co-Cr alloys at high temperatures

    NASA Astrophysics Data System (ADS)

    Ivliyev, A. D.; Glagoleva, Yu. V.

    2011-06-01

    The temperature and concentration dependences of the electrical resistivity ? and thermal diffusivity a of Co-Cr alloys have been studied at temperatures of 400-1600 K. It has been shown that, as the temperature increases, the specific features of the electrical properties of the alloys are mainly determined by phonon scattering of carriers, and the character of the polytherms and concentration dependences is determined by the multiband scattering mechanism.

  9. [Features of overexertion formation due to high psychoemotional strain and shift work].

    PubMed

    Iushkova, O I; Kuz'mina, L P; Poroshenko, A S; Kapustina, A V

    2008-01-01

    Physiologic studies proved that considerable psychoemotional load in shift work and longer working shifts lead to the certain functional state called overexertion. The authors are first to set biochemical and physiologic characteristics by main parameters for this state in mental workers. According to the authors, physiologic features of overexertion should be evaluated from the viewpoint of coordinated diurnal rhythms, internal and intersystem communications in central nervous and cardiovascular systems, functional levels. PMID:18524031

  10. Fiber feature map based landmark initialization for highly deformable DTI registration.

    PubMed

    Gupta, Aditya; Toews, Matthew; Janardhana, Ravikiran; Rathi, Yogesh; Gilmore, John; Escolar, Maria; Styner, Martin

    2013-03-13

    This paper presents a novel pipeline for the registration of diffusion tensor images (DTI) with large pathological variations to normal controls based on the use of a novel feature map derived from white matter (WM) fiber tracts. The research presented aims towards an atlas based DTI analysis of subjects with considerable brain pathologies such as tumors or hydrocephalus. In this paper, we propose a novel feature map that is robust against variations in WM fiber tract integrity and use these feature maps to determine a landmark correspondence using a 3D point correspondence algorithm. This correspondence drives a deformation field computed using Gaussian radial basis functions(RBF). This field is employed as an initialization to a standard deformable registration method like demons. We present early preliminary results on the registration of a normal control dataset to a dataset with abnormally enlarged lateral ventricles affected by fatal demyelinating Krabbe disease. The results are analyzed based on a regional tensor matching criterion and a visual assessment of overlap of major WM fiber tracts. While further evaluation and improvements are necessary, the results presented in this paper highlight the potential of our method in handling registration of subjects with severe WM pathology. PMID:24353392

  11. On the scaling features of high-latitude geomagnetic field fluctuations during a large geomagnetic storm

    NASA Astrophysics Data System (ADS)

    De Michelis, Paola; Federica Marcucci, Maria; Consolini, Giuseppe

    2015-04-01

    Recently we have investigated the spatial distribution of the scaling features of short-time scale magnetic field fluctuations using measurements from several ground-based geomagnetic observatories distributed in the northern hemisphere. We have found that the scaling features of fluctuations of the horizontal magnetic field component at time scales below 100 minutes are correlated with the geomagnetic activity level and with changes in the currents flowing in the ionosphere. Here, we present a detailed analysis of the dynamical changes of the magnetic field scaling features as a function of the geomagnetic activity level during the well-known large geomagnetic storm occurred on July, 15, 2000 (the Bastille event). The observed dynamical changes are discussed in relationship with the changes of the overall ionospheric polar convection and potential structure as reconstructed using SuperDARN data. This work is supported by the Italian National Program for Antarctic Research (PNRA) - Research Project 2013/AC3.08 and by the European Community's Seventh Framework Programme ([FP7/2007-2013]) under Grant no. 313038/STORM and

  12. Probing the gap feature in high Tc superconductors using resonance electronic Raman scattering

    NASA Astrophysics Data System (ADS)

    Klein, M.; Rubhausen, M.; Budelmann, D.; Schulz, B.; Guptasarma, P.; Bonn, D.; Liang, R.; Hardy, W.

    2004-03-01

    We present resonance electronic Raman scattering (RERS) results from the near to optimally doped HTCs Bi-2212 and Y-123 for incident photon energies from 1.96 to 4.5 eV. In RERS the k-space and symmetry dependent Raman amplitude A is tuned by varying the incident photon energy. The local pair susceptibility is multiplied by A^2, "illuminating" those regions of k-space where strong interband transitions occur at the incident photon energy. The resonance behavior of the superconducting gap feature in B_1g symmtery shows changes in shape and peak position as well as an asymmetric resonance profile, approximately 1.5 eV wide. The gap feature shows several components at different energies, which resonate differently with incident photon energy, revealing the composite nature of the gap excitations. Moreover, no superconductivity-induced gap features are visible with photon energies above 3.8 eV, sufficient to excite optical transitions into the buffer layers, suggesting that these buffer layer states do not contribute to superconductivity.

  13. p53 activates G1 checkpoint following DNA damage by doxorubicin during transient mitotic arrest

    PubMed Central

    Hyun, Sun-Yi; Jang, Young-Joo

    2015-01-01

    Recovery from DNA damage is critical for cell survival. The serious damage is not able to be repaired during checkpoint and finally induces cell death to prevent abnormal cell growth. In this study, we demonstrated that 8N-DNA contents are accumulated via re-replication during prolonged recovery period containing serious DNA damage in mitotic cells. During the incubation for recovery, a mitotic delay and initiation of an abnormal interphase without cytokinesis were detected. Whereas a failure of cytokinesis occurred in cells with no relation with p53/p21, re-replication is an anomalous phenomenon in the mitotic DNA damage response in p53/p21 negative cells. Cells with wild-type p53 are accumulated just prior to the initiation of DNA replication through a G1 checkpoint after mitotic DNA damage, even though p53 does not interrupt pre-RC assembly. Finally, these cells undergo cell death by apoptosis. These data suggest that p53 activates G1 checkpoint in response to mitotic DNA damage. Without p53, cells with mitotic DNA damage undergo re-replication leading to accumulation of damage PMID:25605022

  14. Adducin-1 is essential for mitotic spindle assembly through its interaction with myosin-X.

    PubMed

    Chan, Po-Chao; Hsu, Rosaline Y C; Liu, Chih-Wei; Lai, Chien-Chen; Chen, Hong-Chen

    2014-01-01

    Mitotic spindles are microtubule-based structures, but increasing evidence indicates that filamentous actin (F-actin) and F-actin-based motors are components of these structures. ADD1 (adducin-1) is an actin-binding protein that has been shown to play important roles in the stabilization of the membrane cortical cytoskeleton and cell-cell adhesions. In this study, we show that ADD1 associates with mitotic spindles and is crucial for proper spindle assembly and mitotic progression. Phosphorylation of ADD1 at Ser12 and Ser355 by cyclin-dependent kinase 1 enables ADD1 to bind to myosin-X (Myo10) and therefore to associate with mitotic spindles. ADD1 depletion resulted in distorted, elongated, and multipolar spindles, accompanied by aberrant chromosomal alignment. Remarkably, the mitotic defects caused by ADD1 depletion were rescued by reexpression of ADD1 but not of an ADD1 mutant defective in Myo10 binding. Together, our findings unveil a novel function for ADD1 in mitotic spindle assembly through its interaction with Myo10. PMID:24379415

  15. Mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole C1

    PubMed Central

    2010-01-01

    Background Disorazoles are polyene macrodiolides isolated from a myxobacterium fermentation broth. Disorazole C1 was newly synthesized and found to depolymerize microtubules and cause mitotic arrest. Here we examined the cellular responses to disorazole C1 in both non-cancer and cancer cells and compared our results to vinblastine and taxol. Results In non-cancer cells, disorazole C1 induced a prolonged mitotic arrest, followed by mitotic slippage, as confirmed by live cell imaging and cell cycle analysis. This mitotic slippage was associated with cyclin B degradation, but did not require p53. Four assays for apoptosis, including western blotting for poly(ADP-ribose) polymerase cleavage, microscopic analyses for cytochrome C release and annexin V staining, and gel electrophoresis examination for DNA laddering, were conducted and demonstrated little induction of apoptosis in non-cancer cells treated with disorazole C1. On the contrary, we observed an activated apoptotic pathway in cancer cells, suggesting that normal and malignant cells respond differently to disorazole C1. Conclusion Our studies demonstrate that non-cancer cells undergo mitotic slippage in a cyclin B-dependent and p53-independent manner after prolonged mitotic arrest caused by disorazole C1. In contrast, cancer cells induce the apoptotic pathway after disorazole C1 treatment, indicating a possibly significant therapeutic window for this compound. PMID:20181182

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

    PubMed

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

    2015-05-01

    Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G, p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to characterize the effects of EMG1 deficiency, particularly in the brain, where EMG1 expression is high. Embryos homozygous for the mutation in Emg1 were small for gestational age with neural tube defects, and died between embryonic days 8.5 and 12.5. These embryos exhibited dramatically reduced cell proliferation, which we also detected in autopsy brain tissue and bone marrow of BCS patients, consistent with a requirement for high levels of EMG1 in tissues with rapid cell proliferation. In fibroblasts derived from the BCS mouse embryos, we detected a high proportion of binucleated cells, indicating that a mitotic defect underlies the growth arrest in BCS. These studies add to growing evidence of a link between ribosome biogenesis, mitotic progression, and brain development that is currently unexplored. PMID:25708872

  17. Semi-automatic methodologies for landslide features extraction: new opportunities but also challenges from high resolution topography

    NASA Astrophysics Data System (ADS)

    Tarolli, P.; Sofia, G.; Dalla Fontana, G.

    2009-12-01

    In recent years new remotely sensed technologies, such as airborne and terrestrial laser scanner, have improved the detail, and the quality of topographic data with notable advantages over traditional survey techniques (Tarolli et al., 2009). A new generation of high resolution (?3 m) Digital Terrain Models (DTMs) are now available for different areas, and widely used by researchers, offering new opportunities for the scientific community. These data call for the development of the new generation of methodologies for objective extraction of geomorphic features, such as channel heads, channel networks, landslide scars, etc. A high resolution DTM, for example, is able to detect in detail the divergence/convergence areas related to unchannelized/channelized processes respect to a coarse DTM. In last few years different studies used the landform curvature as a useful measure for the interpretation of dominant landform processes (Tarolli and Dalla Fontana, 2009). Curvature has been used to analyze landslide morphology and distribution, and to objectively extract the channel network. In this work, we test the performances of some of these new methodologies for geomorphic features extraction, in order to provide a semi-automatic method to recognize landslide scars in a complex mountainous terrain. The analysis has been carried out using a very high resolution DTM (0.5 m), and different sizes of the moving window for the landform curvature calculation. Statistical dispersion measures (standard deviation, interquartile range, mean and median absolute deviation), and probability plots (quantile-quantile plot) were adopted to objectively define the thresholds of curvature for landslide features extraction. The study was conducted on a study area located in the Eastern Italian Alps, where recent accurate field surveys by DGPS on landslide scars, and a high quality set of airborne laser scanner elevation data are available. The results indicate that curvature maps derived by small moving window sizes are not so representative of local morphology. They do not explore a sufficient range at which landslide features occur. The curvature maps derived by larger moving window sizes overcome this problem, resulting more appropriate for the extraction of surveyed features. The results of our work highlight the capability, but also the challenges of adopted analysis in automated methodologies for geomorphic feature extraction. References Tarolli, P., J R. Arrowsmith, and E. R. Vivoni (2009), Understanding earth surface processes from remotely sensed digital terrain models, Geomorphology, doi:10.1016/j.geomorph.2009.07.005. Tarolli, P., and G. Dalla Fontana (2009), Hillslope-to-valley transition morphology: new opportunities from high resolution DTMs, Geomorphology, doi:10.1016/j.geomorph.2009.02.006.

  18. 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.

  19. 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: luzhiyun@scu.edu.cn, E-mail: jsyu@uestc.edu.cn [State Key Laboratory of Electronic Thin Films and Integrated Devices, School of Optoelectronic Information, University of Electronic Science and Technology of China, Chengdu 610054 (China); Zhou, Jie; Lu, Zhiyun, E-mail: luzhiyun@scu.edu.cn, E-mail: jsyu@uestc.edu.cn [College of Chemistry, Sichuan University, Chengdu 610064 (China)

    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.

  20. Retrieval of ocean colour from high resolution multi?spectral imagery for monitoring highly dynamic ocean features

    Microsoft Academic Search

    Y. H. Ahn; P. Shanmugam; J. E. Moon

    2006-01-01

    Retrieval of ocean colour information from a space borne Multi?spectral Camera (MSC) on KOMPSAT?2 is investigated to study and characterize small?scale biogeophysical features that are very rich and dynamic in nature in the coastal oceans rather than the interior. Prior to the derivation of this information from space?borne ocean colour observations, the path radiance largely from the atmospheric path and

  1. Mapping Low-Level Features to High-Level Semantic Concepts in Region-Based Image Retrieval

    Microsoft Academic Search

    Wei Jiang; Kap Luk Chan; Mingjing Li; Hongjiang Zhang

    2005-01-01

    In this a novel supervised learning method is proposed to map low-level visual features to high-level semantic conceptsfor region-based image retrieval. The contributions of this paper lie in threefolds. (I) For each semantic concept, a set of low-level tokens are extracted f m m the segmented regions of training images. Those to- kens capture the representative information for describing the

  2. 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.

  3. Numerical simulation and investigation of working process features in high-duty combustion chambers

    Microsoft Academic Search

    G. P. Kalmykov; A. A. Larionov; D. A. Sidlerov; L. A. Yanchilin

    2008-01-01

    Basic concepts of a numerical simulation method of two-phase turbulent flows with combustion are stated. Results of computations\\u000a in gas generators and combustion chambers of liquid-propellant rocket engines operating on oxygen and methane are presented.\\u000a Features of the processes of evaporation, mixture, flow, and combustion of the propellant within chambers with tree types\\u000a of injectors, i.e., coaxial-jet gas-liquid, liquid-liquid monopropellant

  4. Theory of High-Energy Features in the Tunneling Spectra of Quantum-Hall Systems

    NASA Astrophysics Data System (ADS)

    MacDonald, A. H.

    2010-11-01

    We show that the low-temperature sash features in lowest Landau-level (LLL) tunneling spectra recently discovered by Dial and Ashoori are intimately related to the discrete Haldane-pseudopotential interaction energy scales that govern fractional quantum-Hall physics. Our analysis is based on expressions for the tunneling density of states which become exact at filling factors close to ?=0 and ?=1, where the sash structure is most prominent. We comment on other aspects of LLL correlation physics that can be revealed by accurate temperature-dependent tunneling data.

  5. Pancreaticobiliary reflux as a high-risk factor for biliary malignancy: Clinical features and diagnostic advancements

    PubMed Central

    Sugita, Reiji

    2015-01-01

    Pancreaticobiliary junction is composed of complex structure with which biliary duct and pancreatic duct assemble and go out into the ampulla of Vater during duodenum wall surrounding the sphincter of Oddi. Although the sphincter of Oddi functionally prevents the reflux of pancreatic juice, pancreaticobiliary reflux (PBR) occurs when function of the sphincter of Oddi halt. The anatomically abnormal junction is termed pancreaticobiliary maljunction (PBM) and is characterized by pancreatic and bile ducts joining outside of the duodenal wall. PBM is an important anatomical finding because many studies have revealed that biliary malignancies are related due to the carcinogenetic effect of the pancreatic back flow on the biliary mucosa. On the other hand, several studies have been published on the reflux of pancreatic juice into the bile duct without morphological PBM, and the correlation of such cases with biliary diseases, especially biliary malignancies, is drawing considerable attention. Although it has long been possible to diagnose PBM by various imaging modalities, PBR without PBM has remained difficult to assess. Therefore, the pathological features of PBR without PBM have not been yet fully elucidated. Lately, a new method of diagnosing PBR without PBM has appeared, and the features of PBR without PBM should soon be better understood.

  6. Automatic analysis of dividing cells in live cell movies to detect mitotic delays and correlate phenotypes in time

    PubMed Central

    Harder, Nathalie; Mora-Bermúdez, Felipe; Godinez, William J.; Wünsche, Annelie; Eils, Roland; Ellenberg, Jan; Rohr, Karl

    2009-01-01

    Live-cell imaging allows detailed dynamic cellular phenotyping for cell biology and, in combination with small molecule or drug libraries, for high-content screening. Fully automated analysis of live cell movies has been hampered by the lack of computational approaches that allow tracking and recognition of individual cell fates over time in a precise manner. Here, we present a fully automated approach to analyze time-lapse movies of dividing cells. Our method dynamically categorizes cells into seven phases of the cell cycle and five aberrant morphological phenotypes over time. It reliably tracks cells and their progeny and can thus measure the length of mitotic phases and detect cause and effect if mitosis goes awry. We applied our computational scheme to annotate mitotic phenotypes induced by RNAi gene knockdown of CKAP5 (also known as ch-TOG) or by treatment with the drug nocodazole. Our approach can be readily applied to comparable assays aiming at uncovering the dynamic cause of cell division phenotypes. PMID:19797680

  7. Mitotic Spindle Integrity and Kinetochore Function Linked by the Duo1p/Dam1p Complex

    PubMed Central

    Cheeseman, Iain M.; Enquist-Newman, Maria; Müller-Reichert, Thomas; Drubin, David G.; Barnes, Georjana

    2001-01-01

    Duo1p and Dam1p were previously identified as spindle proteins in the budding yeast, Saccharomyces cerevisiae. Here, analyses of a diverse collection of duo1 and dam1 alleles were used to develop a deeper understanding of the functions and interactions of Duo1p and Dam1p. Based on the similarity of mutant phenotypes, genetic interactions between duo1 and dam1 alleles, interdependent localization to the mitotic spindle, and Duo1p/Dam1p coimmunoprecipitation from yeast protein extracts, these analyses indicated that Duo1p and Dam1p perform a shared function in vivo as components of a protein complex. Duo1p and Dam1p are not required to assemble bipolar spindles, but they are required to maintain metaphase and anaphase spindle integrity. Immunofluorescence and electron microscopy of duo1 and dam1 mutant spindles revealed a diverse variety of spindle defects. Our results also indicate a second, previously unidentified, role for the Duo1p/Dam1p complex. duo1 and dam1 mutants show high rates of chromosome missegregation, premature anaphase events while arrested in metaphase, and genetic interactions with a subset of kinetochore components consistent with a role in kinetochore function. In addition, Duo1p and Dam1p localize to kinetochores in chromosome spreads, suggesting that this complex may serve as a link between the kinetochore and the mitotic spindle. PMID:11149931

  8. Speaker Verification Using Support Vector Machines and High-Level Features

    Microsoft Academic Search

    William M. Campbell; Joseph P. Campbell; Terry P. Gleason; Douglas A. Reynolds; Wade Shen

    2007-01-01

    High-level characteristics such as word usage, pronunciation, phonotactics, prosody, etc., have seen a resurgence for automatic speaker recognition over the last several years. With the availability of many conversation sides per speaker in current corpora, high-level systems now have the amount of data needed to sufficiently characterize a speaker. Although a significant amount of work has been done in finding

  9. Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features

    Microsoft Academic Search

    Alison R Yung; Lisa J Phillips; Hok Pan Yuen; Patrick D McGorry

    2004-01-01

    The identification of individuals at high risk of developing a psychotic disorder has long been a goal of clinicians because it is thought that early treatment of this group may prevent onset of the disorder. However, little is known of predictive factors of psychosis, even within a high-risk group. This study followed up 104 young people thought to be at

  10. High-resolution spectra of solar magnetic features. II - Magnetic fields of umbral brightenings

    NASA Technical Reports Server (NTRS)

    Lites, Bruce W.; Bida, Thomas A.; Johannesson, A.; Scharmer, G. B.

    1991-01-01

    The spectra of Fe I and Fe II Zeeman-sensitive lines enhanced by video processing of CCD images are considered. The magnetic-field variation within umbras is obtained from the nearly complete Zeeman splitting of the Stokes I profile. It is shown that small brightenings within umbrae have magnetic fields nearly equal to or slightly smaller than that of the darker surroundings; these features are also nearly at rest with respect to their surroundings. It is noted that the absence of significant motions in umbral dots implies that radiation transports most of the energy at and immediately below the surface. The small size of the dots implies that, if convective plumes transport energy below the surface of sunspot umbrae, they should have both a lateral extent and a depth of their upper boundary comparable to or smaller than the size of the dot.

  11. Bcl-xL controls a switch between cell death modes during mitotic arrest.

    PubMed

    Bah, N; Maillet, L; Ryan, J; Dubreil, S; Gautier, F; Letai, A; Juin, P; Barillé-Nion, S

    2014-01-01

    Antimitotic agents such as microtubule inhibitors (paclitaxel) are widely used in cancer therapy while new agents blocking mitosis onset are currently in development. All these agents impose a prolonged mitotic arrest in cancer cells that relies on sustained activation of the spindle assembly checkpoint and may lead to subsequent cell death by incompletely understood molecular events. We have investigated the role played by anti-apoptotic Bcl-2 family members in the fate of mitotically arrested mammary tumor cells treated with paclitaxel, or depleted in Cdc20, the activator of the anaphase promoting complex. Under these conditions, a weak and delayed mitotic cell death occurs that is caspase- and Bax/Bak-independent. Moreover, BH3 profiling assays indicate that viable cells during mitotic arrest are primed to die by apoptosis and that Bcl-xL is required to maintain mitochondrial integrity. Consistently, Bcl-xL depletion, or treatment with its inhibitor ABT-737 (but not with the specific Bcl-2 inhibitor ABT-199), during mitotic arrest converts cell response to antimitotics to efficient caspase and Bax-dependent apoptosis. Apoptotic priming under conditions of mitotic arrest relies, at least in part, on the phosphorylation on serine 62 of Bcl-xL, which modulates its interaction with Bax and its sensitivity to ABT-737. The phospho-mimetic S62D-Bcl-xL mutant is indeed less efficient than the corresponding phospho-deficient S62A-Bcl-xL mutant in sequestrating Bax and in protecting cancer cells from mitotic cell death or yeast cells from Bax-induced growth inhibition. Our results provide a rationale for combining Bcl-xL targeting to antimitotic agents to improve clinical efficacy of antimitotic strategy in cancer therapy. PMID:24922075

  12. 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.

  13. High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features.

    PubMed

    Sciallis, Andrew P; Bedroske, Patrick P; Schoolmeester, John K; Sukov, William R; Keeney, Gary L; Hodge, Jennelle C; Bell, Debra A

    2014-09-01

    The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management. PMID:25133706

  14. Using high level dialogue information for dialogue act recognition using prosodic features

    E-print Network

    Wright, Helen; Poesio, Massimo; Isard, Stephen

    1999-01-01

    We look at the effect of using high level discourse knowledge in dialogue act type detection. We also look at ways this knowledge can be used for improving language modelling and intonation modelling of utterance types. ...

  15. Classification of Epilepsy Using High-Order Spectra Features and Principle Component Analysis

    Microsoft Academic Search

    Xian Du; Sumeet Dua; Rajendra U. Acharya; Chua Kuang Chua

    The classification of epileptic electroencephalogram (EEG) signals is challenging because of high nonlinearity, high dimensionality,\\u000a and hidden states in EEG recordings. The detection of the preictal state is difficult due to its similarity to the ictal state.\\u000a We present a framework for using principal components analysis (PCA) and a classification method for improving the detection\\u000a rate of epileptic classes. To

  16. res2+, a new member of the cdc10+/SWI4 family, controls the 'start' of mitotic and meiotic cycles in fission yeast.

    PubMed Central

    Miyamoto, M; Tanaka, K; Okayama, H

    1994-01-01

    In the fission yeast Schizosaccharomyces pombe, the cdc10+ and res1+ genes play a crucial role in the start of mitotic and meiotic cycles. They encode structurally related transcriptional complex proteins and regulate some S phase-specific genes. Here we report the identification of a new member of this family named as res2+. res2+ has been isolated as a multicopy suppressor of a res1- null mutant and specifies a 73 kDa protein, which has two copies of the Swi/ankyrin motif and shares the highest sequence and structure similarity with the Res1 protein. res2+ is largely redundant in function with res1+ and is required for the initiation of mitotic and premeiotic DNA synthesis, but has an additional role in meiotic division. Unlike res1+, res2+ is highly induced during conjugation and strongly depends on cdc10+ for its activity. We conclude that the fission yeast contains two functionally overlapping parallel 'start' systems, Res1-Cdc10 and Res2-Cdc10, the former of which plays a major role in mitotic cycle whereas the latter in meiotic cycle. Images PMID:8168485

  17. Studies of intestinal lymphoid tissue. VIII. Use of epithelial lymphocyte mitotic indices in differentiating untreated celiac sprue mucosa from other childhood enteropathies.

    PubMed

    Marsh, M N; Miller, V

    1985-12-01

    The mitotic activity of epithelial lymphocytes (expressed as percentage mitotic figures/3,000 lymphocytes/mucosal biopsy) was determined in a random sample of jejunal biopsies performed on 44 children with malabsorption, diarrhoea, or failure to thrive. The mitotic index (MI) exceeded 0.2% in 19 biopsies obtained from children with untreated celiac sprue (CS); there were no false positives. The remaining 25 biopsies (MI of less than 0.2%) were considered to be "nonceliac" in origin, among which were several with a severe degree of villous flattening. Conditions in this latter category excluded by a low MI included cow's milk protein enteropathy, selective immunoglobulin A deficiency, combined variable immunodeficiency, Crohn's jejunitis, and intractable diarrhoea of infancy. A high MI (greater than 0.2%) prospectively distinguishes mucosal lesions due to untreated CS from other causes of malabsorption, particularly those associated with villous flattening, but in which the MI is less than 0.2%. This index is therefore proposed as a simple, reliable, and prospective histological marker of CS, and one that could: reduce the need to perform multiple biopsies during a gluten-free diet; and avoid the necessity for follow-up "diagnostic" gluten challenges, especially in very young children. PMID:4067781

  18. 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.

  19. Moving Magnetic Features Around AR 10930 from High-resolution Data Observed by Hinode/SOT

    NASA Astrophysics Data System (ADS)

    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.

  20. A high dynamic Micro Strips Ionization Chamber featuring Embedded Multi DSP Processing

    E-print Network

    Voltolina, Francesco; Carrato, Sergio; 10.1109/NSSMIC.2004.1466924

    2010-01-01

    An X-ray detector will be presented that is the combination of a segmented ionization chamber featuring one-dimensional spatial resolution integrated with an intelligent ADC front-end, multi DSP processing and embedded PC platform. This detector is optimized to fan beam geometry with an active area of 192 mm (horizontal) and a vertical acceptance of 6 mm. Spatial resolution is obtained by subdividing the anode into readout strips, having pitch of 150 micrometers, which are connected to 20 custom made integrating VLSI chips (each capable of 64-channel read-out and multiplexing) and read out by 14 bits 10 MHz ADCs and fast adaptive PGAs into DSP boards. A bandwidth reaching 3.2Gbit/s of raw data, generated from the real time sampling of the 1280 micro strips, is cascaded processed with FPGA and DSP to allow data compression resulting in several days of uninterrupted acquisition capability. Fast acquisition rates reaching 10 kHz are allowed due to the MicroCAT structure utilized not only as a shielding grid in i...

  1. Mitotic chromosome length scales in response to both cell and nuclear size.

    PubMed

    Ladouceur, Anne-Marie; Dorn, Jonas F; Maddox, Paul S

    2015-06-01

    Multicellular development requires that cells reduce in size as a result of consecutive cell divisions without increase in embryo volume. To maintain cellular integrity, organelle size adapts to cell size throughout development. During mitosis, the longest chromosome arm must be shorter than half of the mitotic spindle for proper chromosome segregation. Using high-resolution time-lapse microscopy of living Caenorhabditis elegans embryos, we have quantified the relation between cell size and chromosome length. In control embryos, chromosome length scaled to cell size. Artificial reduction of cell size resulted in a shortening of chromosome length, following a trend predicted by measurements from control embryos. Disturbing the RAN (Ras-related nuclear protein)-GTP gradient decoupled nuclear size from cell size and resulted in chromosome scaling to nuclear size rather than cell size; smaller nuclei contained shorter chromosomes independent of cell size. In sum, quantitative analysis relating cell, nuclear, and chromosome size predicts two levels of chromosome length regulation: one through cell size and a second in response to nuclear size. PMID:26033258

  2. Nuclear calmodulin/62 kDa calmodulin-binding protein complexes in interphasic and mitotic cells.

    PubMed

    Portolés, M; Faura, M; Renau-Piqueras, J; Iborra, F J; Saez, R; Guerri, C; Serratosa, J; Rius, E; Bachs, O

    1994-12-01

    We report here that a 62 kDa calmodulin-binding protein (p62), recently identified in the nucleus of rat hepatocytes, neurons and glial cells, consists of four polypeptides showing pI values between 5.9 and 6.1. By using a DNA-binding overlay assay we found that the two most basic of the p62 polypeptides bind both single- and double-stranded DNA. The intranuclear distribution of calmodulin and p62 was analysed in hepatocytes and astrocyte precursor cells, and in proliferating and differentiated astrocytes in primary cultures by immunogold-labeling methods. In non-dividing cells nuclear calmodulin was mostly localized in heterochromatin although it was also present in euchromatin and nucleoli. A similar pattern was observed for p62, with the difference that it was not located in nucleoli. p62/calmodulin complexes, mainly located over heterochromatin domains were also observed in interphasic cells. These complexes remained associated with the nuclear matrix after in situ sequential extraction with nucleases and high-salt containing buffers. In dividing cells, both calmodulin and p62 were found distributed over all the mitotic chromosomes but the p62/calmodulin aggregates were disrupted. These results suggest a role for calmodulin and p62 in the condensation of the chromatin. PMID:7706409

  3. Revertant mosaicism in a human skin fragility disorder results from slipped mispairing and mitotic recombination

    PubMed Central

    Kiritsi, Dimitra; He, Yinghong; Pasmooij, Anna M.G.; Onder, Meltem; Happle, Rudolf; Jonkman, Marcel F.; Bruckner-Tuderman, Leena; Has, Cristina

    2012-01-01

    Spontaneous gene repair, also called revertant mosaicism, has been documented in several genetic disorders involving organs that undergo self-regeneration, including the skin. Genetic reversion may occur through different mechanisms, and in a single individual, the mutation can be repaired in various ways. Here we describe a disseminated pattern of revertant mosaicism observed in 6 patients with Kindler syndrome (KS), a genodermatosis caused by loss of kindlin-1 (encoded by FERMT1) and clinically characterized by patchy skin pigmentation and atrophy. All patients presented duplication mutations (c.456dupA and c.676dupC) in FERMT1, and slipped mispairing in direct nucleotide repeats was identified as the reversion mechanism in all investigated revertant skin spots. The sequence around the mutations demonstrated high propensity to mutations, favoring both microinsertions and microdeletions. Additionally, in some revertant patches, mitotic recombination generated areas with homozygous normal keratinocytes. Restoration of kindlin-1 expression led to clinically and structurally normal skin. Since loss of kindlin-1 severely impairs keratinocyte proliferation, we predict that revertant cells have a selective advantage that allows their clonal expansion and, consequently, the improvement of the skin condition. PMID:22466645

  4. TPPP/p25 promotes tubulin assemblies and blocks mitotic spindle formation

    PubMed Central

    Tirián, L.; Hlavanda, E.; Oláh, J.; Horváth, I.; Orosz, F.; Szabó, B.; Kovács, J.; Szabad, J.; Ovádi, J.

    2003-01-01

    Recently, we isolated from bovine brain a protein, TPPP/p25 and identified as p25, a brain-specific protein that induced aberrant tubulin assemblies. The primary sequence of this protein differs from that of other proteins identified so far; however, it shows high homology with p25-like hypothetical proteins sought via blast. Here, we characterized the binding of TPPP/p25 to tubulin by means of surface plasmon resonance; the kinetic parameters are as follows: kon, 2.4 × 104 M–1·s–1; koff, 5.4 × 10–3 s–1; and Kd, 2.3 × 10–7 M. This protein at substoichometric concentration promotes the polymerization of tubulin into double-walled tubules and polymorphic aggregates or bundles paclitaxel-stabilized microtubules as judged by quantitative data of electron and atomic force microscopies. Injection of bovine TPPP/p25 into cleavage Drosophila embryos expressing tubulin–GFP fusion protein reveals that TPPP/p25 inhibits mitotic spindle assembly and nuclear envelope breakdown without affecting other cellular events like centrosome replication and separation, microtubule nucleation by the centrosomes, and nuclear growth. GTP counteracts TPPP/p25 both in vitro and in vivo. PMID:14623963

  5. TPPP/p25 promotes tubulin assemblies and blocks mitotic spindle formation.

    PubMed

    Tirián, L; Hlavanda, E; Oláh, J; Horváth, I; Orosz, F; Szabó, B; Kovács, J; Szabad, J; Ovádi, J

    2003-11-25

    Recently, we isolated from bovine brain a protein, TPPP/p25 and identified as p25, a brain-specific protein that induced aberrant tubulin assemblies. The primary sequence of this protein differs from that of other proteins identified so far; however, it shows high homology with p25-like hypothetical proteins sought via blast. Here, we characterized the binding of TPPP/p25 to tubulin by means of surface plasmon resonance; the kinetic parameters are as follows: kon, 2.4 x 10(4) M(-1) x s(-1); koff, 5.4 x 10(-3) s(-1); and Kd, 2.3 x 10(-7) M. This protein at substoichometric concentration promotes the polymerization of tubulin into double-walled tubules and polymorphic aggregates or bundles paclitaxel-stabilized microtubules as judged by quantitative data of electron and atomic force microscopies. Injection of bovine TPPP/p25 into cleavage Drosophila embryos expressing tubulin-GFP fusion protein reveals that TPPP/p25 inhibits mitotic spindle assembly and nuclear envelope breakdown without affecting other cellular events like centrosome replication and separation, microtubule nucleation by the centrosomes, and nuclear growth. GTP counteracts TPPP/p25 both in vitro and in vivo. PMID:14623963

  6. Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness

    SciTech Connect

    Tran, Truong-An; Gillet, Ludovic; Roger, Sebastien; Besson, Pierre [Inserm, U921, 37000 Tours (France); Universite Francois-Rabelais, 37000 Tours (France); White, Edward [Institute of Membrane and Systems Biology, University of Leeds, LS2 9JT LEEDS (United Kingdom); Le Guennec, Jean-Yves [Inserm, U921, 37000 Tours (France); Universite Francois-Rabelais, 37000 Tours (France)], E-mail: Jean-Yves.LeGuennec@Univ-Tours.Fr

    2009-02-06

    Taxol is widely used in breast cancer chemotherapy. Its effects are primarily attributed to its anti-mitotic activity. Microtubule perturbators also exert antimetastatic activities which cannot be explained solely by the inhibition of proliferation. Voltage-dependent sodium channels (Na{sub V}) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting Na{sub V} activity with tetrodotoxin is responsible for an approximately 0.4-fold reduction of MDA-MB-231 cell invasiveness. In this study, we focused on the effect of a single, 2-h application of 10 nM taxol on the two cell lines MDA-MB-231 and MDA-MB-468. At this concentration, taxol had no effect on proliferation after 7 days and on migration in any cell line. However it led to a 40% reduction of transwell invasion of MDA-MB-231 cells. There was no additive effect when taxol and tetrodotoxin were simultaneously applied. Na{sub V} activity, as assessed by patch-clamp, indicates that it was changed by taxol pre-treatment. We conclude that taxol can exert anti-tumoral activities, in cells expressing Na{sub V}, at low doses that have no effect on cell proliferation. This effect might be due to a modulation of signalling pathways involving sodium channels.

  7. HIGH-pT Features of z-SCALING at Rhic and Tevatron

    NASA Astrophysics Data System (ADS)

    Tokarev, M. V.; Zborovsky, I.; Dedovich, T. G.

    2008-09-01

    Experimental data on inclusive cross sections of jet, direct photon, and high-pT hadron production in pp/bar pp and AA collisions are analyzed in the framework of z-scaling. The analysis is performed with data obtained at ISR, Sbar ppS, RHIC, and Tevatron. Scaling properties of z-presentation of the inclusive spectra are verified. Physical interpretation of the variable z and the scaling function ?(z) is discussed. We argue that general principles of self-similarity, locality, and fractality reflect the structure of the colliding objects, interaction of their constituents, and particle formation at small scales. The obtained results suggest that the z-scaling may be used as a tool for searching for new physics phenomena beyond Standard Model in hadron and nucleus collisions at high transverse momentum and high multiplicity at U70, RHIC, Tevatron, and LHC.

  8. Essential tension and constructive destruction: the spindle checkpoint and its regulatory links with mitotic exit

    PubMed Central

    2004-01-01

    Replicated genetic material must be partitioned equally between daughter cells during cell division. The precision with which this is accomplished depends critically on the proper functioning of the mitotic spindle. The assembly, orientation and attachment of the spindle to the kinetochores are therefore constantly monitored by a surveillance mechanism termed the SCP (spindle checkpoint). In the event of malfunction, the SCP not only prevents chromosome segregation, but also inhibits subsequent mitotic events, such as cyclin destruction (mitotic exit) and cytokinesis. This concerted action helps to maintain temporal co-ordination among mitotic events. It appears that the SCP is primarily activated by either a lack of occupancy or the absence of tension at kinetochores. Once triggered, the inhibitory circuit bifurcates, where one branch restrains the sister chromatid separation by inhibiting the E3 ligase APCCdc20 (anaphase-promoting complex activated by Cdc20) and the other impinges on the MEN (mitotic exit network). A large body of investigations has now led to the identification of the control elements, their targets and the functional coupling among them. Here we review the emerging regulatory network and discuss the remaining gaps in our understanding of this effective mechanochemical control system. PMID:15521820

  9. Phosphorylation–dephosphorylation cycle of HP1? governs accurate mitotic progression

    PubMed Central

    Chakraborty, Arindam; Prasanth, Supriya G

    2014-01-01

    Heterochromatin protein 1? (HP1?), a bona fide factor of silent chromatin, is required for establishing as well as maintaining the higher-order chromatin structure in eukaryotes. HP1? is decorated with several post-translational modifications, and many of these are critical for its cellular functions. HP1? is heavily phosphorylated; however, its physiological relevance had remained to be completely understood. We have recently demonstrated that human HP1? is a mitotic target for NDR kinase, and the phosphorylation at the hinge region of HP1? at the G2/M phase of the cell cycle is crucial for mitotic progression and Sgo1 loading at mitotic centromeres (Chakraborty et al., 2014). We now demonstrate that the dephosphorylation of HP1? within its hinge domain occurs during mitosis, specifically soon after prometaphase. In the absence of the hinge-specific HP1? phosphorylation, either as a consequence of depleting NDR1 or in cells expressing a non-phosphorylatable HP1? mutant, the cells arrest in prometaphase with several mitotic defects. In this study we show that NDR1-depleted cells expressing hinge-specific phosphomimetic HP1? mutant rescues the prometaphase arrest but displays defects in mitotic exit, suggesting that the dephosphorylation of HP1? is required for the completion of cytokinesis. Taken together, our results reveal that the phosphorylation–dephosphorylation cycle of HP1? orchestrates accurate progression of cells through mitosis. PMID:24786771

  10. Electro-acoustic behavior of the mitotic spindle: a semi-classical coarse-grained model.

    PubMed

    Havelka, Daniel; Ku?era, Ond?ej; Deriu, Marco A; Cifra, Michal

    2014-01-01

    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells--a strategy used in novel methods for cancer treatment. PMID:24497952

  11. Electro-Acoustic Behavior of the Mitotic Spindle: A Semi-Classical Coarse-Grained Model

    PubMed Central

    Havelka, Daniel; Ku?era, Ond?ej; Deriu, Marco A.; Cifra, Michal

    2014-01-01

    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells—a strategy used in novel methods for cancer treatment. PMID:24497952

  12. Mitotic rate and S-phase fraction as prognostic factors in stage I cutaneous malignant melanoma.

    PubMed Central

    Karjalainen, J. M.; Eskelinen, M. J.; Nordling, S.; Lipponen, P. K.; Alhava, E. M.; Kosma, V. M.

    1998-01-01

    Clinical data from 369 patients with clinical stage I cutaneous malignant melanoma treated in Kuopio University Hospital district between 1974 and 1989 with a mean follow-up of 6.4 years were analysed. Clinical parameters, histology, DNA index, S-phase fraction (SPF) and mitotic indices [mitotic activity index (MAI) and volume-corrected mitotic index (M/V index)] were correlated with the outcome of the disease to establish their value as predictors of stage I cutaneous malignant melanoma. In univariate survival analyses, bleeding, gender, tumour thickness, level of invasion according to Clark, TNM category, MAI, M/V index and SPF were the most significant predictors of recurrence-free (RFS) and overall survival. In Cox's multivariate analysis, tumour thickness (P = 0.0021), bleeding (P = 0.0106) and M/V index (P = 0.0058) predicted poor RFS in the 259 patients available for the analysis. Poor overall survival was predicted by MAI (P = 0.0002), bleeding (P = 0.004), SPF (P = 0.009) and male gender (P = 0.034). The present results indicate that mitotic activity index (MAI), volume-corrected mitotic index (M/V index) and S-phase fraction (SPF) are important prognostic factors in addition to the well-established Breslow thickness in stage I cutaneous malignant melanoma. PMID:9667668

  13. Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation

    PubMed Central

    Kuga, T; Nie, H; Kazami, T; Satoh, M; Matsushita, K; Nomura, F; Maeshima, K; Nakayama, Y; Tomonaga, T

    2014-01-01

    The majority of human cancer shows chromosomal instability (CIN). Although the precise mechanism remains largely uncertain, proper progression of mitosis is crucial. B-type lamins were suggested to be components of the spindle matrix of mitotic cells and to be involved in mitotic spindle assembly; thus, B-type lamins may contribute to the maintenance of chromosome integrity. Here, using a proteomic approach, we identified lamin B2 as a novel protein involved in CIN. Lamin B2 expression decreased in colorectal cancer cell lines exhibiting CIN, as compared with colorectal cancer cell lines exhibiting microsatellite instability (MIN), which is mutually exclusive to CIN. Importantly, lamin B2 knockdown in MIN-type colorectal cancer cells induced CIN phenotypes such as aneuploidy, chromosome mis-segregation and aberrant spindle assembly, whereas ectopic expression of lamin B2 in CIN-type colorectal cancer cells prevented their CIN phenotypes. Additionally, immunohistochemical analysis showed a lower expression of lamin B2 in cancer tissues extracted from patients with sporadic colorectal cancer (CIN-type) than that from patients with hereditary non-polyposis colorectal cancer (HNPCC; MIN type). Intriguingly, mitotic lamin B2 in MIN cancer cells was localized outside the spindle poles and mitotic lamin B2 localization was diminished in CIN cancer cells, suggesting an important role of lamin B2 in proper mitotic spindle formation. The obtained results suggest that lamin B2 maintains chromosome integrity by ensuring proper spindle assembly and that its downregulation causes CIN in colorectal cancer. PMID:24637494

  14. UV-C irradiation delays mitotic progression by recruiting Mps1 to kinetochores

    PubMed Central

    Zhang, Xiaojuan; Ling, Youguo; Wang, Wenjun; Zhang, Yanhong; Ma, Qingjun; Tan, Pingping; Song, Ting; Wei, Congwen; Li, Ping; Liu, Xuedong; Ma, Runlin Z.; Zhong, Hui; Cao, Cheng; Xu, Quanbin

    2013-01-01

    The effect of UV irradiation on replicating cells during interphase has been studied extensively. However, how the mitotic cell responds to UV irradiation is less well defined. Herein, we found that UV-C irradiation (254 nm) increases recruitment of the spindle checkpoint proteins Mps1 and Mad2 to the kinetochore during metaphase, suggesting that the spindle assembly checkpoint (SAC) is reactivated. In accordance with this, cells exposed to UV-C showed delayed mitotic progression, characterized by a prolonged chromosomal alignment during metaphase. UV-C irradiation also induced the DNA damage response and caused a significant accumulation of ?-H2AX on mitotic chromosomes. Unexpectedly, the mitotic delay upon UV-C irradiation is not due to the DNA damage response but to the relocation of Mps1 to the kinetochore. Further, we found that UV-C irradiation activates Aurora B kinase. Importantly, the kinase activity of Aurora B is indispensable for full recruitment of Mps1 to the kinetochore during both prometaphase and metaphase. Taking these findings together, we propose that UV irradiation delays mitotic progression by evoking the Aurora B-Mps1 signaling cascade, which exerts its role through promoting the association of Mps1 with the kinetochore in metaphase. PMID:23531678

  15. Localized mold heating with the aid of selective induction for injection molding of high aspect ratio micro-features

    NASA Astrophysics Data System (ADS)

    Park, Keun; Lee, Sang-Ik

    2010-03-01

    High-frequency induction is an efficient, non-contact means of heating the surface of an injection mold through electromagnetic induction. Because the procedure allows for the rapid heating and cooling of mold surfaces, it has been recently applied to the injection molding of thin-walled parts or micro/nano-structures. The present study proposes a localized heating method involving the selective use of mold materials to enhance the heating efficiency of high-frequency induction heating. For localized induction heating, a composite injection mold of ferromagnetic material and paramagnetic material is used. The feasibility of the proposed heating method is investigated through numerical analyses in terms of its heating efficiency for localized mold surfaces and in terms of the structural safety of the composite mold. The moldability of high aspect ratio micro-features is then experimentally compared under a variety of induction heating conditions.

  16. Urban building damage detection from very high resolution imagery using OCSVM and spatial features

    Microsoft Academic Search

    Peijun Li; Haiqing Xu; Jiancong Guo

    2010-01-01

    The availability of commercial very high resolution (VHR) satellite imagery makes it possible to detect and assess building damage in the aftermath of earthquake disasters using these data. Although conventional change detection methods may be used to assess the building damage, the analysis is directed to all classes, both damaged and undamaged, but is not focused on the class of

  17. Genetically predisposed offspring with schizotypal features: An ultra high-risk group for schizophrenia?

    Microsoft Academic Search

    Vaibhav A. Diwadkar; Debra M. Montrose; Diana Dworakowski; John A. Sweeney; Matcheri S. Keshavan

    2006-01-01

    Biomarkers proposed in the schizophrenia diathesis have included neurocognitive deficits in domains such as working memory that implicate prefrontal systems. However, the relationship between these biomarkers and psychopathological markers such as schizotypy has not been systematically assessed, particularly in adolescent offspring of schizophrenia patients. Convergence between these markers may identify individuals at especially high risk for schizophrenia. In the current

  18. SS-ClusterTree: a subspace clustering based indexing algorithm over high-dimensional image features

    Microsoft Academic Search

    Hongli Xu; Dantong Yu; De Xu; Aidong Zhang

    2008-01-01

    The rapid growth in the volume of image and video data collections motivates the research of building an index structure in image information retrieval. Constructing an index in the image database poses a very challenging problem due to the facts of image databases containing data with high dimensions, and lack of domain knowledge. ClusterTree is an indexing approach representing clusters

  19. Mapping electrodynamic features of the high-latitude ionosphere from localized observations - Technique

    Microsoft Academic Search

    A. D. Richmond; Y. Kamide

    1988-01-01

    This paper describes a novel procedure for mapping high-latitude electric fields and currents and their associated magnetic variations, using sets of localized observational data derived from different types of measurements. The technique provides a formalism for incorporating simultaneously such different classes of data as electric fields from radars and satellites, electric currents from radars, and magnetic perturbations at the ground

  20. 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…

  1. 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,..).

  2. High-cycle fatigue crack paths in specimens having different stress concentration features

    Microsoft Academic Search

    G. Meneghetti; L. Susmel; R. Tovo

    2007-01-01

    This paper summarises an attempt to study the high-cycle fatigue cracking behaviour in specimens of low carbon steel weakened by U-notches. The specimens were tested under uniaxial fatigue loading with a load ratio equal to 0.1, and the considered Kt values, calculated with respect to the gross area, ranged from 3.8 up to about 25. The generated crack paths were

  3. Relationships among repetitive behaviors, sensory features, and executive functions in high functioning autism

    Microsoft Academic Search

    Brian A. Boyd; Matthew McBee; Tia Holtzclaw; Grace T. Baranek; James W. Bodfish

    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 explained any relationship between the variables. Particular types of repetitive behavior (i.e., stereotypy and compulsions)

  4. Astro-H: New Spectral Features Seen in High-Resolution X-rays

    NASA Astrophysics Data System (ADS)

    Smith, Randall K.; Odaka, Hirokazu; Astro-H Science Working Group

    2015-01-01

    The Soft X-ray Spectrometer (SXS) microcalorimeter on Astro-H will provide the first high-resolution X-ray spectra of diffuse astrophysical sources. One key new type of science will be charge exchange spectroscopy, wherein highly-ionized metals interact with neutral hydrogen, helium, or other material. This has been detected with modest resolution in comets and planets, and is thought to be the origin of at least some of the 1/4 keV soft X-ray background. We will report on the predicted emission that the Astro-H SXS may detector from all of these sources using the recently released AtomdB Charge Exchange spectral model acx, and comment on possible other sources such as starburst galaxies. The SXS will also observe complex high-resolution spectra from other diffuse sources such as overionized supernova remnants and galaxy clusters. We will discuss these in the context of advanced spectral models using the recently released AtomDB v3.0 data and non-equilibrium models.

  5. 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

  6. Cell fate after mitotic arrest in different tumor cells is determined by the balance between slippage and apoptotic threshold

    SciTech Connect

    Galán-Malo, Patricia; Vela, Laura; Gonzalo, Oscar; Calvo-Sanjuán, Rubén; Gracia-Fleta, Lucía; Naval, Javier; Marzo, Isabel, E-mail: imarzo@unizar.es

    2012-02-01

    Microtubule poisons and other anti-mitotic drugs induce tumor death but the molecular events linking mitotic arrest to cell death are still not fully understood. We have analyzed cell fate after mitotic arrest produced by the microtubule-destabilizing drug vincristine in a panel of human tumor cell lines showing different response to vincristine. In Jurkat, RPMI 8226 and HeLa cells, apoptosis was triggered shortly after vincristine-induced mitotic arrest. However, A549 cells, which express a great amount of Bcl-x{sub L} and undetectable amounts of Bak, underwent mitotic slippage prior to cell death. However, when Bcl-x{sub L} gene was silenced in A549 cells, vincristine induced apoptosis during mitotic arrest. Another different behavior was found in MiaPaca2 cells, where vincristine caused death by mitotic catastrophe that switched to apoptosis when cyclin B1 degradation was prevented by proteasome inhibition. Overexpression of Bcl-x{sub L} or silencing Bax and Bak expression delayed the onset of apoptosis in Jurkat and RPMI 8226 cells, enabling mitotic slippage and endoreduplication. In HeLa cells, overexpression of Bcl-x{sub L} switched cell death from apoptosis to mitotic catastrophe. Mcl-1 offered limited protection to vincristine-induced cell death and Mcl-1 degradation was not essential for vincristine-induced death. All these results, taken together, indicate that the Bcl-x{sub L}/Bak ratio and the ability to degrade cyclin B1 determine cell fate after mitotic arrest in the different tumor cell types. Highlights: ? Vincristine induces cell death by apoptosis or mitotic catastrophe. ? Apoptosis-proficient cells die by apoptosis during mitosis upon vincristine treatment. ? p53wt apoptosis-deficient cells undergo apoptosis from a G1-like tetraploid state. ? p53mt apoptosis-deficient cells can survive and divide giving rise to 8N cells.

  7. Condensed Mitotic Chromosome Structure at Nanometer Resolution Using PALM and EGFP- Histones

    PubMed Central

    Matsuda, Atsushi; Shao, Lin; Boulanger, Jerome; Kervrann, Charles; Carlton, Peter M.; Kner, Peter; Agard, David; Sedat, John W.

    2010-01-01

    Photoactivated localization microscopy (PALM) and related fluorescent biological imaging methods are capable of providing very high spatial resolutions (up to 20 nm). Two major demands limit its widespread use on biological samples: requirements for photoactivatable/photoconvertible fluorescent molecules, which are sometimes difficult to incorporate, and high background signals from autofluorescence or fluorophores in adjacent focal planes in three-dimensional imaging which reduces PALM resolution significantly. We present here a high-resolution PALM method utilizing conventional EGFP as the photoconvertible fluorophore, improved algorithms to deal with high levels of biological background noise, and apply this to imaging higher order chromatin structure. We found that the emission wavelength of EGFP is efficiently converted from green to red when exposed to blue light in the presence of reduced riboflavin. The photon yield of red-converted EGFP using riboflavin is comparable to other bright photoconvertible fluorescent proteins that allow <20 nm resolution. We further found that image pre-processing using a combination of denoising and deconvolution of the raw PALM images substantially improved the spatial resolution of the reconstruction from noisy images. Performing PALM on Drosophila mitotic chromosomes labeled with H2AvD-EGFP, a histone H2A variant, revealed filamentous components of ?70 nm. This is the first observation of fine chromatin filaments specific for one histone variant at a resolution approximating that of conventional electron microscope images (10–30 nm). As demonstrated by modeling and experiments on a challenging specimen, the techniques described here facilitate super-resolution fluorescent imaging with common biological samples. PMID:20856676

  8. A nontranscriptional role for Oct4 in the regulation of mitotic entry

    PubMed Central

    Zhao, Rui; Deibler, Richard W.; Lerou, Paul H.; Ballabeni, Andrea; Heffner, Garrett C.; Cahan, Patrick; Unternaehrer, Juli J.; Kirschner, Marc W.; Daley, George Q.

    2014-01-01

    Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin–Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry. PMID:25324523

  9. High Constitutive Activity Is an Intrinsic Feature of Ghrelin Receptor Protein

    PubMed Central

    Damian, Marjorie; Marie, Jacky; Leyris, Jean-Philippe; Fehrentz, Jean-Alain; Verdié, Pascal; Martinez, Jean; Banères, Jean-Louis; Mary, Sophie

    2012-01-01

    Despite its central role in signaling and the potential therapeutic applications of inverse agonists, the molecular mechanisms underlying G protein-coupled receptor (GPCR) constitutive activity remain largely to be explored. In this context, ghrelin receptor GHS-R1a is a peculiar receptor in the sense that it displays a strikingly high, physiologically relevant, constitutive activity. To identify the molecular mechanisms responsible for this high constitutive activity, we have reconstituted a purified GHS-R1a monomer in a lipid disc. Using this reconstituted system, we show that the isolated ghrelin receptor per se activates Gq in the absence of agonist, as assessed through guanosine 5?-O-(thiotriphosphate) binding experiments. The measured constitutive activity is similar in its extent to that observed in heterologous systems and in vivo. This is the first direct evidence for the high constitutive activity of the ghrelin receptor being an intrinsic property of the protein rather than the result of influence of its cellular environment. Moreover, we show that the isolated receptor in lipid discs recruits arrestin-2 in an agonist-dependent manner, whereas it interacts with ?-AP2 in the absence of ligand or in the presence of ghrelin. Of importance, these differences are linked to ligand-specific GHS-R1a conformations, as assessed by intrinsic fluorescence measurements. The distinct ligand requirements for the interaction of purified GHS-R1a with arrestin and AP2 provide a new rationale to the differences in basal and agonist-induced internalization observed in cells. PMID:22117076

  10. Simulating thermal stress features on hot planetary surfaces in vacuum at high temperature facility in the PEL laboratory

    NASA Astrophysics Data System (ADS)

    Maturilli, A.; Ferrari, S.; Helbert, J.; D'Incecco, P.; D'Amore, M.

    2011-12-01

    In the Planetary Emissivity Laboratory (PEL) at the Institute for Planetary Research of the German Aerospace Center (DLR) in Berlin, we set-up a simulation chamber for the spectroscopic investigation of minerals separates under Mercurial conditions. The chamber can be evacuated to 10-4 bar and the target samples heated to 700 K within few minutes, thanks to the innovative inductive heating system. While developing the protocol for the high temperature spectroscopy measurements we discovered interesting "morphologies" on the sample surfaces. The powders are poured into stainless steel cups of 50 mm internal diameter, 8 mm height and 3 mm depth, having a 5 mm thick base (thus leaving 3 mm free space for the minerals), and rim 1 mm thick. We selected several minerals of interest for Mercurial surface composition and for each of them we analyzed various grain size separates, to study the influence of grain dimensions to the process of thermal stressing. We observed that for the smaller grain size separate (0-25 ?m) the thermal stress mainly induces large depressions and fractures, while on larger grain sizes (125-250 ?m) small depressions and a cratered surface. Our current working hypothesis is that these features are mainly caused by thermal stress induced by a radiatively quickly cooling surface layer covering the much hotter bulk material. Further investigation is ongoing to understand the processes better. The observed morphologies exhibit surprising similarities to features observed at planetary scale size for example on Mercury and even on Venus. Especially the high resolution images provided currently from MESSENGER'S Mercury Dual Imaging System (MDIS) instrument has revealed plains dominated by polygonal fractures whose origin still have to be determined. Our laboratory analogue studies might in the future provide some insight into the processes creating those features

  11. GeoNet: Nonlinear filtering and geodesic minimization principles for geomorphic feature extraction from high resolution topographic data

    NASA Astrophysics Data System (ADS)

    Passalacqua, P.; Stark, C. P.; Sangireddy, H.

    2011-12-01

    The detection of channel networks and the localization of channel heads from digital terrain model (DTM) data are fundamental to the accurate modeling of water, sediment, and other environmental fluxes in a watershed. With the availability of high resolution topographic data obtained by airborne laser mapping, the direct detection of geomorphic features such as channels is now possible, instead of indirect inference using derived quantities such as slope and drainage area. At the same time, the impressive resolution of lidar data comes with a price: new tools are needed for the automatic and objective extraction of geomorphic features from the enormous amount of information contained in such DTMs. The GeoNet software package carries out the automatic extraction of channel networks, channel heads and channel morphology from high-resolution topographic data. Pre-processing of the data is performed through nonlinear filtering, via partial differential equations, which removes small scale variability while enhancing features of interest. The form of this filtering is such that it behaves as linear diffusion at low elevation gradients, while it arrests diffusion as the gradients become large. Channel detection is performed by solving an eikonal equation through the fast marching algorithm. Channels are thus detected as curves of minimal cost, or geodesics, where the cost is defined in physically meaningful terms using local geomorphic attributes derived from the DTM. GeoNet is now at its third release as free software. This talk will focus on the technical aspects of the software and in particular on the new improved performance of its latest release.

  12. Emergence of a new feature in the high pressure-high temperature relaxation spectrum of tri-propylene glycol

    NASA Astrophysics Data System (ADS)

    Prevosto, D.; Capaccioli, S.; Lucchesi, M.; Rolla, P. A.; Paluch, M.; Pawlus, S.; Zio?o, J.

    2005-02-01

    We investigated dielectric relaxation of a tri-propylene glycol system under high compression. By increasing temperature and pressure we observed that a new relaxation process emerges from the low frequency tail of the structural peak. This new peak starts to be visible at about 0.5 GPa and becomes clearly evident at 1.7 GPa. However, this additional peak merges again with the structural one as the glass transition is approached, since it has a weaker temperature dependence. This finding enriches the relaxation scenario of molecular glass formers confirming that the application of very high hydrostatic pressure can favor the detection of new relaxation or otherwise unresolved processes in supercooled liquid systems.

  13. High-speed AFM for 1x node metrology and inspection: Does it damage the features?

    NASA Astrophysics Data System (ADS)

    Sadeghian, Hamed; van den Dool, Teun C.; Uziel, Yoram; Bar Or, Ron

    2015-03-01

    This paper aims at unraveling the mystery of damage in high speed AFMs for 1X node and below. With the device dimensions moving towards the 1X node and below, the semiconductor industry is rapidly approaching the point where existing metrology, inspection and review tools face huge challenges in terms of resolution, the ability to resolve 3D, and throughput. In this paper, we critically asses the important issue of damage in high speed AFM for metrology and inspection of semiconductor wafers. The issues of damage in four major scanning modes (contact mode, tapping mode, non-contact mode, and peak force tapping mode) are described to show which modes are suitable for which applications and which conditions are damaging. The effects of all important scanning parameters on resulting damage are taken into account for materials such as silicon, photoresists and low K materials. Finally, we recommend appropriate scanning parameters and conditions for several use cases (FinFET, patterned photoresist, HAR structures) that avoid exceeding a critical contact stress such that sample damage is minimized. In conclusion, we show using our theoretical analysis that selecting parameters that exceed the target contact stress, indeed leads to significant damage. This method provides AFM users for metrology with a better understanding of contact stresses and enables selection of AFM cantilevers and experimental parameters that prevent sample damage.

  14. Evaluation of properties and special features for high-temperature applications of rhenium

    NASA Astrophysics Data System (ADS)

    Bryskin, Boris D.

    1992-01-01

    Sixty-six years have passes since rhenium was discovered in June 1925 by husband-and-wife team Walter and Ida Noddack. The rapid development of rhenium is due to the unique properties of the metal and its alloys. Rhenium has a hexagonal close packed structure as opposed to the body centered cubic structure of other refractory metals. Rhenium does not have a ductile to brittle transition temperature and retains its ductility from sub zero to elevated temperatures. Rhenium work-hardens at a higher rate and to a greater degree than any other unalloyed metal known. Hot deformation is feasible only in a non-oxidizing shielding atmosphere. Refractory metal alloys have found use as heating elements, compact electromagnet coils, high temperature thermocouples, anti-friction and low wear parts, and high temperature elastic elements. One major development area for pure rhenium is in the aerospace industry, as in the SP-100 Program. Due to their unique properties, rhenium and its alloys are being considered for many areas in space applications.

  15. 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

  16. SAP-like domain in nucleolar spindle associated protein mediates mitotic chromosome loading as well as interphase chromatin interaction

    SciTech Connect

    Verbakel, Werner, E-mail: werner.verbakel@chem.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)] [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium); Carmeliet, Geert, E-mail: geert.carmeliet@med.kuleuven.be [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium)] [Laboratory of Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Herestraat 49, Bus 902, 3000 Leuven (Belgium); Engelborghs, Yves, E-mail: yves.engelborghs@fys.kuleuven.be [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)] [Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Bus 2403, 3001 Heverlee (Belgium)

    2011-08-12

    Highlights: {yields} The SAP-like domain in NuSAP is a functional DNA-binding domain with preference for dsDNA. {yields} This SAP-like domain is essential for chromosome loading during early mitosis. {yields} NuSAP is highly dynamic on mitotic chromatin, as evident from photobleaching experiments. {yields} The SAP-like domain also mediates NuSAP-chromatin interaction in interphase nucleoplasm. -- Abstract: Nucleolar spindle associated protein (NuSAP) is a microtubule-stabilizing protein that localizes to chromosome arms and chromosome-proximal microtubules during mitosis and to the nucleus, with enrichment in the nucleoli, during interphase. The critical function of NuSAP is underscored by the finding that its depletion in HeLa cells results in various mitotic defects. Moreover, NuSAP is found overexpressed in multiple cancers and its expression levels often correlate with the aggressiveness of cancer. Due to its localization on chromosome arms and combination of microtubule-stabilizing and DNA-binding properties, NuSAP takes a special place within the extensive group of spindle assembly factors. In this study, we identify a SAP-like domain that shows DNA binding in vitro with a preference for dsDNA. Deletion of the SAP-like domain abolishes chromosome arm binding of NuSAP during mitosis, but is not sufficient to abrogate its chromosome-proximal localization after anaphase onset. Fluorescence recovery after photobleaching experiments revealed the highly dynamic nature of this NuSAP-chromatin interaction during mitosis. In interphase cells, NuSAP also interacts with chromatin through its SAP-like domain, as evident from its enrichment on dense chromatin regions and intranuclear mobility, measured by fluorescence correlation spectroscopy. The obtained results are in agreement with a model where NuSAP dynamically stabilizes newly formed microtubules on mitotic chromosomes to enhance chromosome positioning without immobilizing these microtubules. Interphase NuSAP-chromatin interaction suggests additional functions for NuSAP, as recently identified for other nuclear spindle assembly factors with a role in gene expression or DNA damage response.

  17. High-risk angina patient: identification by clinical features, hospital course, electrocardiography, and technetium-99m stannous pyrophosphate scintigraphy

    SciTech Connect

    Olson, H.G. (Univ. of California, Irvine); 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.

  18. 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.

  19. The importance of study design for detecting differentially abundant features in high-throughput experiments.

    PubMed

    Luo, Huaien; Li, Juntao; Chia, Burton Kuan Hui; Robson, Paul; Nagarajan, Niranjan

    2014-01-01

    High-throughput assays, such as RNA-seq, to detect differential abundance are widely used. Variable performance across statistical tests, normalizations, and conditions leads to resource wastage and reduced sensitivity. EDDA represents a first, general design tool for RNA-seq, Nanostring, and metagenomic analysis, that rationally selects tests, predicts performance, and plans experiments to minimize resource wastage. Case studies highlight EDDA's ability to model single-cell RNA-seq, suggesting ways to reduce sequencing costs up to five-fold and improving metagenomic biomarker detection through improved test selection. EDDA's novel mode-based normalization for detecting differential abundance improves robustness by 10% to 20% and precision by up to 140%. PMID:25517037

  20. Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features

    PubMed Central

    Lassmann, Timo; Frings, Oliver; Sonnhammer, Erik L. L.

    2009-01-01

    In the growing field of genomics, multiple alignment programs are confronted with ever increasing amounts of data. To address this growing issue we have dramatically improved the running time and memory requirement of Kalign, while maintaining its high alignment accuracy. Kalign version 2 also supports nucleotide alignment, and a newly introduced extension allows for external sequence annotation to be included into the alignment procedure. We demonstrate that Kalign2 is exceptionally fast and memory-efficient, permitting accurate alignment of very large numbers of sequences. The accuracy of Kalign2 compares well to the best methods in the case of protein alignments while its accuracy on nucleotide alignments is generally superior. In addition, we demonstrate the potential of using known or predicted sequence annotation to improve the alignment accuracy. Kalign2 is freely available for download from the Kalign web site (http://msa.sbc.su.se/). PMID:19103665

  1. Building feature extraction via a deterministic approach: applicationto real high resolution SAR images

    Microsoft Academic Search

    Giorgio Franceschetti; Raffaella Guida; Antonio Iodice; Daniele Riccio; Giuseppe Ruello; U. Stilla

    2007-01-01

    Interpretation of high resolution SAR (synthetic aperture radar) images\\u000d\\u000a\\u0009is still a hard task, especially when man-made objects crowd the\\u000d\\u000a\\u0009scene under detection. This paper contributes to the analysis of\\u000d\\u000a\\u0009this kind of data by adopting an approach, based on a scattering\\u000d\\u000a\\u0009model, for the retrieval of buildings height from real SAR images\\u000d\\u000a\\u0009and presenting first numerical results.

  2. 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

  3. Features of highly structured equatorial plasma irregularities deduced from CHAMP observations

    NASA Astrophysics Data System (ADS)

    Xiong, C.; Lühr, H.; Ma, S. Y.; Stolle, C.; Fejer, B. G.

    2012-08-01

    In this study five years of CHAMP (Challenging Mini-satellite Payload) fluxgate magnetometer (FGM) data is used to investigate the characteristics of Equatorial Plasma Bubbles (EPBs). We filtered the FGM data by using band-passes with four different cut-off periods to get the EPBs with different maximum spatial scale sizes in the meridional plane ranging from 76-608 km. Associated with the EPB observations at about 400 km, the typical altitude of CHAMP during the year 2000-2005, we also investigate the post-sunset equatorial vertical plasma drift data from ROCSAT-1 (Republic of China Satellite 1). Since the height of the F-layer is highly correlated with the vertical plasma drift and solar flux, we sorted the ROCSAT-1 data into different groups by F10.7. From the integrated vertical drift we have estimated the post-sunset uplift of the ionosphere. By comparing the properties of EPB occurrence for different scale sizes with the global distribution of plasma vertical uplift, we have found that EPBs reaching higher altitudes are more structured than those which are sampled by CHAMP near the top side of the depleted fluxtube. Such a result is in accord with 3-D model simulations (Aveiro and Hysell, 2010). Small-scale EPB structures are observed by CHAMP when the irregularities reach apex heights of 800 km and more. Such events are encountered primarily in the Brazilian sector during the months around November, when the post-sunset vertical plasma drift is high.

  4. High Sensitivity to Auxin is a Common Feature of Hairy Root 1

    PubMed Central

    Shen, Wen Hui; Davioud, Elisabeth; David, Chantal; Barbier-Brygoo, Hélène; Tempé, Jacques; Guern, Jean

    1990-01-01

    The responses to auxin of Lycopersicon esculentum roots transformed by (Tl+Tr)-DNA of the Ri plasmid of agropine-type Agrobacterium rhizogenes strain 15834 and Catharanthus trichophyllus roots transformed by the (Tl+Tr)-DNA, and by Tl- or Tr- DNA alone of the same bacterial strain were compared to that of their normal counterparts. The transmembrane electrical potential difference of root protoplasts was measured as a function of the concentration of exogenous naphthalene acetic acid. The sensitivity to auxin expressed by this response was shown to be independent of the measurement conditions and of the basal polarization of isolated protoplasts. According to this electrical response, as well as to the modulation by auxin of proton excretion by root tips and root tip elongation, roots transformed by (Tl+Tr) DNA are 100 to 1000 times more sensitive to exogenous auxin than normal roots, as is the case with normal and transformed roots from Lotus corniculatus (WH Shen, A Petit, J Guern, J Tempé [1988] Proc Natl Acad Sci USA 85: 3417-3421). Further-more, transformed roots of C. trichophyllus are not modified in their sensitivity to fusicoccin, illustrating the specificity of the modification of the auxin sensitivity. Roots transformed by the Tr-DNA alone showed the same sensitivity to auxin as normal roots, whereas the roots transformed by the Tl-DNA alone exhibited an auxin sensitivity as high as the roots transformed by (Tl+Tr)-DNA. It was concluded that the high sensitivity to auxin is controlled by the Tl-DNA in agropine type Ri plasmids. PMID:16667748

  5. The Caenorhabditis elegans THO Complex Is Required for the Mitotic Cell Cycle and Development

    PubMed Central

    Castellano-Pozo, Maikel; García-Muse, Tatiana; Aguilera, Andrés

    2012-01-01

    THO is a conserved eukaryotic complex involved in mRNP biogenesis and RNA export that plays an important role in preventing transcription- and RNA-mediated genome instability in mitosis and meiosis. In mammals THO is essential for embryogenesis, which limits our capacity to analyze the physiological relevance of THO during development and in adult organisms. Using Caenorhabditis elegans as a model system we show that the THO complex is essential for mitotic genome integrity and the developmentally regulated mitotic cell cycles occurring during late postembryonic stages. PMID:23285047

  6. 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

  7. Identification and partial characterization of mitotic centromere- associated kinesin, a kinesin-related protein that associates with centromeres during mitosis

    Microsoft Academic Search

    Linda Wordeman; Timothy J. Mitchison

    1995-01-01

    Using antipeptide antibodies to conserved regions of the kinesin motor domain, we cloned a kinesin-related protein that associates with the centro- mere region of mitotic chromosomes. We call the pro- tein MCAK, for mitotic centromere-associated kinesin. MCAK appears concentrated on centromeres at prophase and persists until telophase, after which time the localization disperses. It is found throughout the centromere region

  8. Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent

    SciTech Connect

    McNeely, Samuel C.; Taylor, B. Frazier [Department of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine and Brown Cancer Center, University of Louisville, 570 S. Preston St. Suite 221, Louisville, KY 40202 (United States); States, J. Christopher [Department of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine and Brown Cancer Center, University of Louisville, 570 S. Preston St. Suite 221, Louisville, KY 40202 (United States)], E-mail: jcstates@louisville.edu

    2008-08-15

    A375 human malignant melanoma cells undergo mitotic arrest-associated apoptosis when treated with pharmacological concentrations of sodium arsenite, a chemotherapeutic for acute promyelocytic leukemia. Our previous studies indicated that decreased arsenite sensitivity correlated with reduced mitotic spindle checkpoint function and reduced expression of the checkpoint protein BUBR1. In the current study, arsenite induced securin and cyclin B stabilization, BUBR1 phosphorylation, and spindle checkpoint activation. Arsenite also increased activating cyclin dependent kinase 1 (CDK1) Thr{sup 161} phosphorylation but decreased inhibitory Tyr15 phosphorylation. Mitotic arrest resulted in apoptosis as indicated by colocalization of mitotic phospho-Histone H3 with active caspase 3. Apoptosis was associated with BCL-2 Ser70 phosphorylation. Inhibition of CDK1 with roscovitine in arsenite-treated mitotic cells inhibited spindle checkpoint maintenance as inferred from reduced BUBR1 phosphorylation, reduced cyclin B expression, and diminution of mitotic index. Roscovitine also reduced BCL-2 Ser70 phosphorylation and protected against apoptosis, suggesting mitotic arrest caused by hyperactivation of CDK1 directly or indirectly leads to BCL-2 phosphorylation and apoptosis. In addition, suppression of BUBR1 with siRNA prevented arsenite-induced mitotic arrest and apoptosis. These findings provide insight into the mechanism of arsenic's chemotherapeutic action and indicate a functional spindle checkpoint may be required for arsenic-sensitivity.

  9. A Temperature-Dependent Index of Mitotic Interval (?0) for Chromosome Manipulation in Paddlefish and Shovelnose Sturgeon

    Microsoft Academic Search

    William L. Shelton; Steven D. Mims; Julia A. Clark; Ana E. Hiott; Changzheng Wang

    1997-01-01

    A temperature-dependent measure of the mitotic interval (?0) can help standardize chromosome manipulation in fish eggs. A tau unit (?0) is the duration in minutes of one mitotic cycle during synchronous embryonic cleavage. It is measured over a range of temperatures, and the resulting relationship of ?0 to temperature can be used to anticipiate developmental events that are affected by

  10. Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

    PubMed Central

    Bergman, Zane J.; Mclaurin, Justin D.; Eritano, Anthony S.; Johnson, Brittany M.; Sims, Amanda Q.; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope. PMID:25689737

  11. High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Campylobacter jejuni Isolates

    PubMed Central

    Förstner, Konrad U.; Heidrich, Nadja; Reinhardt, Richard; Nieselt, Kay; Sharma, Cynthia M.

    2013-01-01

    Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA–seq (dRNA–seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA–seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA–seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA–seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into strain-specific transcriptome organization and sRNAs, and reveals genes that could modulate phenotypic variation among strains despite high conservation at the DNA level. PMID:23696746

  12. Capillary-Driven Reflow of Thin Copper Films with Submicron, High Aspect Ratio Features

    NASA Astrophysics Data System (ADS)

    Brain, Ruth Amy

    Conventional sputtering techniques are no longer sufficient for the fabrication of interconnects as trench widths enter the submicron regime and aspect ratios become greater than 1:1. The goal of this thesis is to investigate Cu as a potential interconnect metal for use in integrated circuit technology. Since sputtering is well established in the integrated circuit industry, we have used current sputtering technology as our deposition technique of choice. An alternative approach to modify the nonconformal deposition profiles obtained by sputtering is to reflow (planarize by capillary-driven surface diffusion) the metal film during a post-deposition anneal. In particular, reflow is performed for thin Cu films deposited on refractory metal barrier layers (Mo, Ta, and W) at temperatures <= 500^circC. With a goal of developing and understanding a post-deposition reflow process for Cu, we have studied the following topics. Chapter 1 introduces relevant current concepts in ultra-large scale integration for interconnect technology to motivate the approaches described in this thesis. Chapter 2 investigates several techniques to improve the initial Cu coverage obtained from a magnetron sputtering source. This was found to be necessary since thin Cu films agglomerate on many underlayers. Chapter 3 describes an investigation of the atomic transport mechanism during reflow of Cu films, to understand the kinetics of reflow and measure the appropriate kinetic constants. Extensive transmission electron microscope (TEM) work was done to examine reflowed profiles and to relate the extent of reflow to the microstructure of the Cu films. Hot-stage TEM experiments were performed to observe dynamically the reflow of a very low aspect ratio film. Chapter 4 develops a finite-element model to study surface diffusion mediated reflow in high aspect ratio trenches. We have considered (i) reflow of typical continuum, as-deposited profiles from a magnetron sputtering source, (ii) reflow of continuum profiles including an anisotropic surface energy and (iii) reflow with the inclusion of grain boundaries. We also discuss some limitations of a post-deposition reflow process, and we make recommendations to facilitate the ability to reflow Cu in high aspect ratio trenches. Finally, Chapter 5 examines a microwave annealing technique to reflow Cu films.

  13. Temperature and high pressure effects on the structural features of catalytic nanocomposites oxides by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    da Silva, Antonio N.; Pinto, Raffael C. F.; Freire, Paulo T. C.; Junior, Jose Alves L.; Oliveira, Alcineia C.; Filho, Josué M.

    2015-03-01

    Structural characterizations of nanostructured oxides were studied by X-ray diffraction (XRD), Raman and infrared spectroscopy. The oxides catalysts namely, SnO2, ZrO2, CeO2, MnOx, Al2O3 and TiO2 were prepared by a nanocasting route and the effect of the temperature and pressure on the stability of the solids was evaluated. Raman spectra showed that ZrO2 and TiO2 exhibited phase transitions at moderate temperatures whereas CeO2, SnO2 and MnOx had an effective creation of defects in their structures upon annealing at elevated temperatures. The results suggested also that the effect of the temperature on the particles growth is related to the type of oxide. In this regard, phase transition by up to 600 °C accelerated the sintering of ZrO2 and CeO2 grains compared to TiO2, SnO2 and MnOx counterparts. Under hydrostatic pressures lower than 10 GPa, rutile TiO2 and tetragonal ZrO2 exhibited pressure induced phase transition whereas CeO2 and SnO2 were stable at pressures close to 15 GPa. The experiments revealed that the nanostructured SnO2 oxide exhibited stable performance at relatively high temperatures without phase transition or sintering, being suitable to be used as catalysts in the range of temperature and pressure studied.

  14. Temperature and high pressure effects on the structural features of catalytic nanocomposites oxides by Raman spectroscopy.

    PubMed

    da Silva, Antonio N; Pinto, Raffael C F; Freire, Paulo T C; Junior, Jose Alves L; Oliveira, Alcineia C; Filho, Josué M

    2015-03-01

    Structural characterizations of nanostructured oxides were studied by X-ray diffraction (XRD), Raman and infrared spectroscopy. The oxides catalysts namely, SnO2, ZrO2, CeO2, MnOx, Al2O3 and TiO2 were prepared by a nanocasting route and the effect of the temperature and pressure on the stability of the solids was evaluated. Raman spectra showed that ZrO2 and TiO2 exhibited phase transitions at moderate temperatures whereas CeO2, SnO2 and MnOx had an effective creation of defects in their structures upon annealing at elevated temperatures. The results suggested also that the effect of the temperature on the particles growth is related to the type of oxide. In this regard, phase transition by up to 600°C accelerated the sintering of ZrO2 and CeO2 grains compared to TiO2, SnO2 and MnOx counterparts. Under hydrostatic pressures lower than 10GPa, rutile TiO2 and tetragonal ZrO2 exhibited pressure induced phase transition whereas CeO2 and SnO2 were stable at pressures close to 15GPa. The experiments revealed that the nanostructured SnO2 oxide exhibited stable performance at relatively high temperatures without phase transition or sintering, being suitable to be used as catalysts in the range of temperature and pressure studied. PMID:25544192

  15. High-resolution spectra of solar magnetic features. I. Analysis of penumbral fine structure

    SciTech Connect

    Lites, B.W.; Skumanich, A.; Scharmer, G.B. (High Altitude Observatory, Boulder, CO (USA) Kungliga Svenska Vetenskapsakademien, Stockholm (Sweden))

    1990-05-01

    The Swedish Vacuum Telescope on La Palma was used to obtain spectra of the magnetic-sensitive Fe I 630.25 nm line under conditions of exceptional angular resolution (0.32 arcsec) and high spectral resolution (FWHM 2.5 pm). Simultaneous 0.02 s CCD exposures of both the spectrum and the slit-jaw image effectively 'freeze' the atmospheric seeing motions and permit unambiguous identification of the spectra of the various penumbral structures. These spectra reveal the magnetic field strength in penumbral filaments through an intensity fit of the Zeeman splitting of this line. The observations show that: (1) the field strength varies from about 2100 G near the umbra-penumbra boundary to about 900 G at the outer edge of the penumbra, (2) the observed fluctuation of penumbral magnetic field is much less dramatic than the fluctuation in intensity, (3) there is a suggestion of a rapid change in field inclination between some light and dark filaments near the edge of the penumbra, and (4) there is no obvious correlation between Doppler shift (in part due to the Evershed flow) and filament intensity. 43 refs.

  16. Two Strains of Crocosphaera watsonii with Highly Conserved Genomes are Distinguished by Strain-Specific Features

    PubMed Central

    Bench, Shellie R.; Ilikchyan, Irina N.; Tripp, H. James; Zehr, Jonathan P.

    2011-01-01

    Unicellular nitrogen-fixing cyanobacteria are important components of marine phytoplankton. Although non-nitrogen-fixing marine phytoplankton generally exhibit high gene sequence and genomic diversity, gene sequences of natural populations and isolated strains of Crocosphaera watsonii, one of the two most abundant open ocean unicellular cyanobacteria groups, have been shown to be 98–100% identical. The low sequence diversity in Crocosphaera is a dramatic contrast to sympatric species of Prochlorococcus and Synechococcus, and raises the question of how genome differences can explain observed phenotypic diversity among Crocosphaera strains. Here we show, through whole genome comparisons of two phenotypically different strains, that there are strain-specific sequences in each genome, and numerous genome rearrangements, despite exceptionally low sequence diversity in shared genomic regions. Some of the strain-specific sequences encode functions that explain observed phenotypic differences, such as exopolysaccharide biosynthesis. The pattern of strain-specific sequences distributed throughout the genomes, along with rearrangements in shared sequences is evidence of significant genetic mobility that may be attributed to the hundreds of transposase genes found in both strains. Furthermore, such genetic mobility appears to be the main mechanism of strain divergence in Crocosphaera which do not accumulate DNA microheterogeneity over the vast majority of their genomes. The strain-specific sequences found in this study provide tools for future physiological studies, as well as genetic markers to help determine the relative abundance of phenotypes in natural populations. PMID:22232617

  17. Vibrational Features of Water at the Low-Density/High-Density Liquid Structural Transformations

    E-print Network

    Khusnutdinoff, Ramil M

    2011-01-01

    A structural transformation in water upon compression was recently observed at the temperature $T=277$~K in the vicinity of the pressure $p \\approx 2\\;000$~Atm [R.M. Khusnutdinoff, A.V. Mokshin, J. Non-Cryst. Solids \\textbf{357}, 1677 (2011)]. It was found that the transformations are related with the principal structural changes within the first two coordination shells as well as the deformation of the hydrogen-bond network. In this work we study in details the influence of these structural transformations on the vibrational molecular dynamics of water by means of molecular dynamics simulations on the basis of the model Amoeba potential ($T=290$~K, $p=1.0 \\div 10\\;000$~Atm). The equation of state and the isothermal compressibility are found for the considered ($p$,$T$)-range. The vibrational density of states extracted for $THz$-frequency range manifests the two distinct modes, where the high-frequency mode is independent on pressure whereas the low-frequency one has the strong, non-monotonic pressure-depend...

  18. Induced Rates of Mitotic Crossing over and Possible Mitotic Gene Conversion per Wing Anlage Cell in Drosophila Melanogaster by X Rays and Fission Neutrons

    PubMed Central

    Ayaki, T.; Fujikawa, K.; Ryo, H.; Itoh, T.; Kondo, S.

    1990-01-01

    As a model for chromosome aberrations, radiation-induced mitotic recombination of mwh and flr genes in Drosophila melanogaster strain (mwh +/+ flr) was quantitatively studied. Fission neutrons were five to six times more effective than X rays per unit dose in producing either crossover-mwh/flr twins and mwh singles--or flr singles, indicating that common processes are involved in the production of crossover and flr singles. The X-ray-induced rate/wing anlage cell/Gy for flr singles was 1 X 10(-5), whereas that of crossover was 2 X 10(-4); the former and the latter rate are of the same order of magnitude as those of gene conversion and crossover in yeast, respectively. Thus, we conclude that proximal-marker ``flr'' singles induced in the transheterozygote are gene convertants. Using the model based on yeast that recombination events result from repair of double-strand breaks or gaps, we propose that mitotic recombination in the fly is a secondary result of recombinational DNA repair. Evidence for recombinational misrepair in the fly is given. The relative ratio of radiation-induced mitotic crossover to spontaneous meiotic crossover is one order of magnitude higher in the fly than in yeast and humans. PMID:2121593

  19. Mapping the Organization of Axis of Motion Selective Features in Human Area MT Using High-Field fMRI

    PubMed Central

    De Martino, Federico; van de Moortele, Pierre-Francois; Feinberg, David; Adriany, Gregor; Chaimow, Denis; Shmuel, Amir; U?urbil, Kamil; Yacoub, Essa

    2011-01-01

    Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1). While the middle temporal area (MT) has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic), optimized coil design, ultrahigh field magnets (7 Tesla) and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations. PMID:22163328

  20. Local changes of work function near rough features on Cu surfaces operated under high external electric field

    SciTech Connect

    Djurabekova, Flyura, E-mail: flyura.djurabekova@helsinki.fi; Ruzibaev, Avaz; Parviainen, Stefan [Helsinki Institute of Physics and Department of Physics, University of Helsinki, P.O. Box 43, FI-00014 Helsinki (Finland); Holmström, Eero [Department of Physics, University of Helsinki, P.O. Box 64, FIN-00014 Helsinki (Finland); Department of Earth Sciences, Faculty of Maths and Physical Sciences, UCL Earth Sciences, Gower Street, London WC1E 6BT (United Kingdom); Hakala, Mikko [Department of Physics, University of Helsinki, P.O. Box 64, FIN-00014 Helsinki (Finland)

    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.

  1. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment

    PubMed Central

    Bertolini, Giulia; Roz, Luca; Perego, Paola; Tortoreto, Monica; Fontanella, Enrico; Gatti, Laura; Pratesi, Graziella; Fabbri, Alessandra; Andriani, Francesca; Tinelli, Stella; Roz, Elena; Caserini, Roberto; Lo Vullo, Salvatore; Camerini, Tiziana; Mariani, Luigi; Delia, Domenico; Calabrò, Elisa; Pastorino, Ugo; Sozzi, Gabriella

    2009-01-01

    The identification of lung tumor-initiating cells and associated markers may be useful for optimization of therapeutic approaches and for predictive and prognostic information in lung cancer patients. CD133, a surface glycoprotein linked to organ-specific stem cells, was described as a marker of cancer-initiating cells in different tumor types. Here, we report that a CD133+, epithelial-specific antigen-positive (CD133+ESA+) population is increased in primary nonsmall cell lung cancer (NSCLC) compared with normal lung tissue and has higher tumorigenic potential in SCID mice and expression of genes involved in stemness, adhesion, motility, and drug efflux than the CD133? counterpart. Cisplatin treatment of lung cancer cells in vitro resulted in enrichment of CD133+ fraction both after acute cytotoxic exposure and in cells with stable cisplatin-resistant phenotype. Subpopulations of CD133+ABCG2+ and CD133+CXCR4+ cells were spared by in vivo cisplatin treatment of lung tumor xenografts established from primary tumors. A tendency toward shorter progression-free survival was observed in CD133+ NSCLC patients treated with platinum-containing regimens. Our results indicate that chemoresistant populations with highly tumorigenic and stem-like features are present in lung tumors. The molecular features of these cells may provide the rationale for more specific therapeutic targeting and the definition of predictive factors in clinical management of this lethal disease. PMID:19805294

  2. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment.

    PubMed

    Bertolini, Giulia; Roz, Luca; Perego, Paola; Tortoreto, Monica; Fontanella, Enrico; Gatti, Laura; Pratesi, Graziella; Fabbri, Alessandra; Andriani, Francesca; Tinelli, Stella; Roz, Elena; Caserini, Roberto; Lo Vullo, Salvatore; Camerini, Tiziana; Mariani, Luigi; Delia, Domenico; Calabrò, Elisa; Pastorino, Ugo; Sozzi, Gabriella

    2009-09-22

    The identification of lung tumor-initiating cells and associated markers may be useful for optimization of therapeutic approaches and for predictive and prognostic information in lung cancer patients. CD133, a surface glycoprotein linked to organ-specific stem cells, was described as a marker of cancer-initiating cells in different tumor types. Here, we report that a CD133+, epithelial-specific antigen-positive (CD133+ESA+) population is increased in primary nonsmall cell lung cancer (NSCLC) compared with normal lung tissue and has higher tumorigenic potential in SCID mice and expression of genes involved in stemness, adhesion, motility, and drug efflux than the CD133(-) counterpart. Cisplatin treatment of lung cancer cells in vitro resulted in enrichment of CD133+ fraction both after acute cytotoxic exposure and in cells with stable cisplatin-resistant phenotype. Subpopulations of CD133+ABCG2+ and CD133+CXCR4+ cells were spared by in vivo cisplatin treatment of lung tumor xenografts established from primary tumors. A tendency toward shorter progression-free survival was observed in CD133+ NSCLC patients treated with platinum-containing regimens. Our results indicate that chemoresistant populations with highly tumorigenic and stem-like features are present in lung tumors. The molecular features of these cells may provide the rationale for more specific therapeutic targeting and the definition of predictive factors in clinical management of this lethal disease. PMID:19805294

  3. Design features of a high-intensity, cesium-sputter/plasma-sputter negative ion source (abstract)a)

    NASA Astrophysics Data System (ADS)

    Alton, G. D.; Mills, G. D.; Dellwo, J.

    1994-04-01

    A versatile, high-intensity, negative ion source has been designed and is now under construction which can be operated in either the cesium-sputter or plasma-sputter mode. The cesium-sputter mode can be effected by installation of a newly designed conical-geometry cesium-surface ionizer; for operation in the plasma-sputter mode, the surface ionizer is removed and either a hot-filament or rf antenna plasma-discharge igniter is installed. A multicusp magnetic field is specifically provided for confining the plasma in the radial direction when the plasma-sputter mode is selected. This arrangement allows comparison of the two modes of operation. Brief descriptions of the design features, ion optics, and anticipated performances of the two source geometries will be presented in this report.

  4. Exome Sequencing and High-Density Microarray Testing in Monozygotic Twin Pairs Discordant for Features of VACTERL Association.

    PubMed

    Solomon, B D; Pineda-Alvarez, D E; Hadley, D W; Hansen, N F; Kamat, A; Donovan, F X; Chandrasekharappa, S C; Hong, S-K; Roessler, E; Mullikin, J C

    2013-02-01

    Exome sequencing offers an efficient and affordable method to interrogate genetic factors involved in human disease. Performing exome sequencing of monozygotic twins discordant for VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities) association-type congenital malformations was hypothesized to potentially reveal discordant variants that could demonstrate disease cause(s). After demonstrating monozygosity, we applied high-density microarrays and exome sequencing to 2 twin pairs in which 1 twin had features of VACTERL association while the other was phenotypically normal (demonstrated through comprehensive clinical and radiological evaluation). No obvious discordant genotypic results were found that would explain phenotypic discordance. We conclude that VACTERL association is a complex disease, and while performing microarray analysis and exome sequencing on phenotypically discordant monozygotic twins may hypothetically reveal genetic causes of disorders, challenges remain in applying these methods in this circumstance. PMID:23653574

  5. Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability

    PubMed Central

    Lin, Chiou-Hong; Hu, Chi-Kuo

    2010-01-01

    Mitotic spindles play essential roles in chromosome congression and segregation during mitosis. Aurora A regulates spindle assembly in part via phosphorylating human TACC3 on S558, which triggers TACC3 relocalization to mitotic spindles and stabilizes microtubules (MTs). In this study, we identified clathrin heavy chain (CHC) as an adaptor protein to recruit S558-phosphorylated TACC3 onto the spindle during mitosis for MT stabilization. CHC binds phospho-S558 TACC3 via its linker domain and first CHC repeat. CHC depletion or mutation on phospho-TACC3 binding abrogates TACC3 spindle relocalization. Depletion of either or both CHC and TACC3 yields similar defective phenotypes: loss of ch-TOG on spindles, disorganized spindles, and chromosome misalignment with comparable mitotic delay. Our findings elucidate the association between aurora A phosphorylation and spindle apparatus and demonstrate that regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles. PMID:20566684

  6. 80006-3509(96)00053-1 BEHAVIOUR OF THE MITOTIC APPARATUS AFTER

    E-print Network

    Vorobjev, Ivan

    in the metaphase of one of the poles leads to an immediate shift of all the chromosomes to the non-irradiated pole with the kinetochore bundles of the chromosomes and in the metaphase draws nearer to the chromosomes while.v. microirradiation of the centrosome (mitotic spindle pole) on cell division in the metaphase and anaphase

  7. RanBP1 governs spindle assembly by defining mitotic Ran-GTP production.

    PubMed

    Zhang, Michael Shaofei; Arnaoutov, Alexei; Dasso, Mary

    2014-11-24

    Accurate control of the Ras-related nuclear protein (Ran) GTPase cycle depends on the regulated activity of regulator of chromosome condensation 1 (RCC1), Ran's nucleotide exchange factor. RanBP1 has been characterized as a coactivator of the Ran GTPase-activating protein RanGAP1. RanBP1 can also form a stable complex with Ran and RCC1, although the dynamics and function of this complex remain poorly understood. Here, we show that formation of the heterotrimeric RCC1/Ran/RanBP1 complex in M phase Xenopus egg extracts controls both RCC1's enzymatic activity and partitioning between the chromatin-bound and soluble pools of RCC1. This mechanism is critical for spatial control of Ran-guanosine triphosphate (GTP) gradients that guide mitotic spindle assembly. Moreover, phosphorylation of RanBP1 drives changes in the dynamics of chromatin-bound RCC1 pools at the metaphase-anaphase transition. Our findings reveal an important mitotic role for RanBP1, controlling the spatial distribution and magnitude of mitotic Ran-GTP production and thereby ensuring accurate execution of Ran-dependent mitotic events. PMID:25458009

  8. Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold

    E-print Network

    Poirier, Michael

    response of, and then to go on to completely disintegrate, single metaphase newt chromosomes only partially disassemble mitotic chromosomes and indicate that chromatin in metaphase chromo- somes maintenance of chromosomes (7). Further studies indicated that the metaphase scaffold is helically folded (8

  9. EML4 promotes the loading of NUDC to the spindle for mitotic progression.

    PubMed

    Chen, Dan; Ito, Satoko; Yuan, Hong; Hyodo, Toshinori; Kadomatsu, Kenji; Hamaguchi, Michinari; Senga, Takeshi

    2015-05-19

    Echinoderm microtubule-associated protein (EMAP)-like (EML) family proteins are microtubule-associated proteins that have a conserved hydrophobic EMAP-like protein (HELP) domain and multiple WD40 domains. In this study, we examined the role of EML4, which is a member of the EML family, in cell division. Time-lapse microscopy analysis demonstrated that EML4 depletion induced chromosome misalignment during metaphase and delayed anaphase initiation. Further analysis by immunofluorescence showed that EML4 was required for the organization of the mitotic spindle and for the proper attachment of kinetochores to microtubules. We searched for EML4-associating proteins by mass spectrometry analysis and found that the nuclear distribution gene C (NUDC) protein, which is a critical factor for the progression of mitosis, was associated with EML4. This interaction was mediated by the WD40 repeat of EML4 and by the C-terminus of NUDC. In the absence of EML4, NUDC was no longer able to localize to the mitotic spindle, whereas NUDC was dispensable for EML4 localization. Our results show that EML4 is critical for the loading of NUDC onto the mitotic spindle for mitotic progression. PMID:25789526

  10. A mitotic form of the Golgi apparatus in HeLa cells

    Microsoft Academic Search

    John M. Lucocq; James G. Pryde; Eric G. Berger; Graham Warren

    1987-01-01

    Galactosyltransferase, a marker for trans- Golgi cisternae in interphase cells, was localized in mitotic HeLa cells embedded in Lowicryl K4M by im- munoelectron microscopy. Specific labeling was found only over multivesicular structures that we term Golgi clusters. Unlike Golgi stacks in interphase cells, these clusters lacked elongated cisternae and ordered stack- ing of their components but did comprise two distinct

  11. Mitotic chromosomes and the W-sex chromosome of the great horned owl (Bubo V. virginianus)

    Microsoft Academic Search

    Awtar Krishan; G. J. Haiden; R. N. Shoffner

    1965-01-01

    Mitotic chromosomes from the feather pulp and leucocyte cultures of the great horned owl (Bubo v. virginianus) were analyzed in both the sexes. The largest pair of chromosomes are acrocentrics while those of the second and the third pair have a short arm 1\\/6th the size of the large one. Chromosomes of the fourth and the fifth pairs have a

  12. Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling.

    PubMed

    Han, Joo Seok; Vitre, Benjamin; Fachinetti, Daniele; Cleveland, Don W

    2014-10-01

    The mitotic checkpoint (also known as the spindle assembly checkpoint) prevents premature anaphase onset through generation of an inhibitor of the E3 ubiquitin ligase APC/C, whose ubiquitination of cyclin B and securin targets them for degradation. Combining in vitro reconstitution and cell-based assays, we now identify dual mechanisms through which Bub3 promotes mitotic checkpoint signaling. Bub3 enhances signaling at unattached kinetochores not only by facilitating binding of BubR1 but also by enhancing Cdc20 recruitment to kinetochores mediated by BubR1's internal Cdc20 binding site. Downstream of kinetochore-produced complexes, Bub3 promotes binding of BubR1's conserved, amino terminal Cdc20 binding domain to a site in Cdc20 that becomes exposed by initial Mad2 binding. This latter Bub3-stimulated event generates the final mitotic checkpoint complex of Bub3-BubR1-Cdc20 that selectively inhibits ubiquitination of securin and cyclin B by APC/C(Cdc20). Thus, Bub3 promotes two distinct BubR1-Cdc20 interactions, involving each of the two Cdc20 binding sites of BubR1 and acting at unattached kinetochores or cytoplasmically, respectively, to facilitate production of the mitotic checkpoint inhibitor. PMID:25246557

  13. Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability.

    PubMed

    Lin, Chiou-Hong; Hu, Chi-Kuo; Shih, Hsiu-Ming

    2010-06-28

    Mitotic spindles play essential roles in chromosome congression and segregation during mitosis. Aurora A regulates spindle assembly in part via phosphorylating human TACC3 on S558, which triggers TACC3 relocalization to mitotic spindles and stabilizes microtubules (MTs). In this study, we identified clathrin heavy chain (CHC) as an adaptor protein to recruit S558-phosphorylated TACC3 onto the spindle during mitosis for MT stabilization. CHC binds phospho-S558 TACC3 via its linker domain and first CHC repeat. CHC depletion or mutation on phospho-TACC3 binding abrogates TACC3 spindle relocalization. Depletion of either or both CHC and TACC3 yields similar defective phenotypes: loss of ch-TOG on spindles, disorganized spindles, and chromosome misalignment with comparable mitotic delay. Our findings elucidate the association between aurora A phosphorylation and spindle apparatus and demonstrate that regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles. PMID:20566684

  14. Friedreich's Ataxia (GAA)nN(TTC)n Repeats Strongly Stimulate Mitotic Crossovers in Saccharomyces cerevisae

    E-print Network

    Mirkin, Sergei

    Friedreich's Ataxia (GAA)nN(TTC)n Repeats Strongly Stimulate Mitotic Crossovers in Saccharomyces disease Friedreich's ataxia, and long GAANTTC tracts elevate genome instability in yeast. We show. Citation: Tang W, Dominska M, Greenwell PW, Harvanek Z, Lobachev KS, et al. (2011) Friedreich's Ataxia (GAA

  15. Mitotic instability leading to an accumulation of B-chromosomes in grasshoppers

    Microsoft Academic Search

    Uzi Nur

    1969-01-01

    The study of mitotically unstable B-chromosomes (supernumeraries) of two grasshopper species confirmed a suggestion made earlier (Nur, 1963) that the instability should always be associated with a tendency of the B's to increase in frequency. Among 780 Camnula pellucida (Scudder) males from California, 105 had B's. In the testes of these males the number of B's varied from follicle to

  16. Microtubules Orient the Mitotic Spindle in Yeast through Dynein-dependent Interactions with the Cell Cortex

    Microsoft Academic Search

    Janet L. Carminati; Tim Stearns

    1997-01-01

    Proper orientation of the mitotic spindle is critical for successful cell division in budding yeast. To investigate the mechanism of spindle orientation, we used a green fluorescent protein (GFP)-tubulin fusion protein to observe microtubules in living yeast cells. GFP-tubulin is incorporated into microtubules, allow- ing visualization of both cytoplasmic and spindle micro- tubules, and does not interfere with normal microtu-

  17. Polewards microtubule flux in the mitotic spindle: evidence from photoactivation of fluorescence

    Microsoft Academic Search

    T. J. Mitchison

    1989-01-01

    I have synthesized a novel derivative of car- boxyfluorescein that is nonfluorescent, but can be con- verted to a fluorescent form by exposure to 365-nm light. This photoactivable, fluorescent probe was cova- lently attached to tubulin and microinjected into mi- totic tissue culture cells, where it incorporated into functional spindles. To generate a fluorescent bar across the mitotic spindle, metaphase

  18. 2006 Nature Publishing Group Analysis of a RanGTP-regulated gradient in mitotic

    E-print Network

    Pralle, Arnd

    using a biosensor, termed Rango, that increases its fluorescence resonance energy transfer signal when released from importin-b by RanGTP. Rango is predominantly free in mitotic cells, but is further liberated cells, we developed a fluorescence resonance energy transfer (FRET) biosensor termed Rango (Ran

  19. Permissive effects of thyroid hormones on rat anterior pituitary mitotic activity

    Microsoft Academic Search

    L A Nolan; C K Thomas; A Levy

    2004-01-01

    The anterior pituitary is active mitotically and apoptoti- cally under basal conditions and in response to a variety of physiological and pathophysiological stimuli. Hypo- thyroidism in man is associated with a modest but very occasionally dramatic increase in overall pituitary size. The mechanisms underlying this reversible phenomenon remain obscure. In the present study we have examined young adult rat anterior

  20. RanGTP and CLASP1 cooperate to position the mitotic spindle.

    PubMed

    Bird, Stephen L; Heald, Rebecca; Weis, Karsten

    2013-08-01

    Accurate positioning of the mitotic spindle is critical to ensure proper distribution of chromosomes during cell division. The small GTPase Ran, which regulates a variety of processes throughout the cell cycle, including interphase nucleocytoplasmic transport and mitotic spindle assembly, was recently shown to also control spindle alignment. Ran is required for the correct cortical localization of LGN and nuclear-mitotic apparatus protein (NuMA), proteins that generate pulling forces on astral microtubules (MTs) through cytoplasmic dynein. Here we use importazole, a small-molecule inhibitor of RanGTP/importin-? function, to study the role of Ran in spindle positioning in human cells. We find that importazole treatment results in defects in astral MT dynamics, as well as in mislocalization of LGN and NuMA, leading to misoriented spindles. Of interest, importazole-induced spindle-centering defects can be rescued by nocodazole treatment, which depolymerizes astral MTs, or by overexpression of CLASP1, which does not restore proper LGN and NuMA localization but stabilizes astral MT interactions with the cortex. Together our data suggest a model for mitotic spindle positioning in which RanGTP and CLASP1 cooperate to align the spindle along the long axis of the dividing cell. PMID:23783028

  1. Centromeres, the chromosomal sites of attachment to the mitotic spindle, have been familiar to cell biologists

    E-print Network

    Henikoff, Steven

    Centromeres, the chromosomal sites of attachment to the mitotic spindle, have been familiar to cell biologists for well over a century (Fig. 1). Centromeres were evident to Walther Flemming in his landmark. It therefore might come as a surprise that although the segregation function of centromeres was understood

  2. The centrin-based cytoskeleton of Chlamydomonas reinhardtii: distribution in interphase and mitotic cells

    Microsoft Academic Search

    Jeffrey L. Salisbury; Andre T. Baron; Mark A. Sanders

    1988-01-01

    Monoclonal and polyclonal antibodies raised against algal centrin, a protein of algal striated flagellar roots, were used to characterize the occur- rence and distribution of this protein in interphase and mitotic Chlamydomonas cells. Chlamydomonas cen- trin, as identified by Western immunoblot procedures, is a low molecular (20,000-Mr) acidic protein. Im- munofluorescence and immunogold labeling demon- strates that centrin is a

  3. Effects of ovariectomy on estrogen uptake capacity, mitotic index and morphology of immunocytochemically-identified gonadotropes

    SciTech Connect

    Smith, P.F.

    1985-01-01

    The primary objective of these studies was to examine the effects of ovariectomy on the pituitary gonadotrope population in the rat. Several parameters were examined including morphology, mitotic index and ability of individual cells to concentrate estrogen. Adult, female rats which had been ovariectomized 3, 14, or 50 previously, were injected with /sup 3/H-estradiol (i.v.) and killed 1 hour later. Pituitaries were excised and immediately hemisected (mid-sagittal cut). Trunk blood was collected for subsequent radioimmunoassay of serum LH levels to assess the activity of the pituitary gonadotropes. Frozen pituitaries were sectioned and processed for dry-mount autoradiography. Estrogen uptake capacity of gonadotropes increased with time after ovariectomy. This increase was not seen in male rats after castration. Hemi-pituitaries were sectioned (1 ..mu..m) and analyzed for the number of mitotic figures per mm/sup 2/ and dividing cells were characterized as to their hormonal content. Ovariectomy induced an increase in the mitotic index of the pituitary gland. Furthermore, a majority of the mitotic futures seen in the ovariectomized rat were found in cells containing LH-immunoreactivity. Electron microscopic examination of dividing gonadotropes revealed that these cells contained large amounts of vesiculated endoplasmic reticumum typical of post-castration gonadotropes.

  4. Large-scale chromatin structural domains within mitotic and interphase chromosomes in vivo and in vitro

    Microsoft Academic Search

    Andrew S. Belmont; Michael B. Braunfeld; John W. Sedat; David A. Agard

    1989-01-01

    Higher-order chromatin structural domains approximately 130 nm in width are observed as prominent components of both Drosophila melanogaster and human mitotic chromosomes using buffer conditions which preserve chromosome morphology as determined by light microscopic comparison with chromosomes within living cells. Spatially discrete chromatin structural domains of similar size also exist as prominent components within interphase nuclei prepared under equivalent conditions.

  5. A Minimal Cascade Model for the Mitotic Oscillator Involving Cyclin and cdc2 Kinase

    Microsoft Academic Search

    Albert Goldbeter

    1991-01-01

    A minimal model for the mitotic oscillator is presented. The model, built on recent experimental advances, is based on the cascade of post-translational modification that modulates the activity of cdc2 kinase during the cell cycle. The model pertains to the situation encountered in early amphibian embryos, where the accumulation of cyclin suffices to trigger the onset of mitosis. In the

  6. Application of a Temperature-Dependent Mitotic Interval (?o) for Induction of Diploid Meiotic Gynogenetic Paddlefish

    Microsoft Academic Search

    Steven D. Mims; William L. Shelton; Otomar Linhart; Changzheng Wang; Boris Gomelsky; Richard J. Onders

    2005-01-01

    We tested the application of mitotic interval (tau [?o]) unit in comparison with absolute time to help standardize preshock timing for a consistent production of diploid meiotic gynogenetic paddlefish Polyodon spathula. The diploid gynogenetic larvae were produced by applying heat shock (35°C; 2 min) at different times after activation of paddlefish eggs with irradiated sperm of shovelnose sturgeon Scaphirhynchus platorynchus

  7. Multiple phosphorylation events control mitotic degradation of the muscle transcription factor Myf5

    E-print Network

    Doucet, Christine; Gutierrez, Gustavo J; Lindon, Catherine; Lorca, Thierry; Lledo, Gwendaline; Pinset, Christian; Coux, Olivier

    2005-12-01

    of the cell cycle apparatus. Using Xenopus egg extracts as an in vitro system to dissect the main steps of Myf5 mitotic proteolysis, we show that (1) Myf5 stability is regulated by a complex interplay of phosphorylation/dephosphorylation, probably involving...

  8. Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling

    PubMed Central

    Han, Joo Seok; Vitre, Benjamin; Fachinetti, Daniele; Cleveland, Don W.

    2014-01-01

    The mitotic checkpoint (also known as the spindle assembly checkpoint) prevents premature anaphase onset through generation of an inhibitor of the E3 ubiquitin ligase APC/C, whose ubiquitination of cyclin B and securin targets them for degradation. Combining in vitro reconstitution and cell-based assays, we now identify dual mechanisms through which Bub3 promotes mitotic checkpoint signaling. Bub3 enhances signaling at unattached kinetochores not only by facilitating binding of BubR1 but also by enhancing Cdc20 recruitment to kinetochores mediated by BubR1’s internal Cdc20 binding site. Downstream of kinetochore-produced complexes, Bub3 promotes binding of BubR1’s conserved, amino terminal Cdc20 binding domain to a site in Cdc20 that becomes exposed by initial Mad2 binding. This latter Bub3-stimulated event generates the final mitotic checkpoint complex of Bub3–BubR1–Cdc20 that selectively inhibits ubiquitination of securin and cyclin B by APC/CCdc20. Thus, Bub3 promotes two distinct BubR1-Cdc20 interactions, involving each of the two Cdc20 binding sites of BubR1 and acting at unattached kinetochores or cytoplasmically, respectively, to facilitate production of the mitotic checkpoint inhibitor. PMID:25246557

  9. WT1 Interacts with MAD2 and Regulates Mitotic Checkpoint Function

    PubMed Central

    Shandilya, Jayasha; Toska, Eneda; Richard, Derek J; Medler, Kathryn F; Roberts, Stefan GE

    2014-01-01

    SUMMARY Tumor suppressors safeguard the fidelity of the mitotic checkpoint by transcriptional regulation of genes that encode components of the mitotic checkpoint complex (MCC). Here we report a new role for the tumor suppressor and transcription factor, WT1, in the mitotic checkpoint. We show that WT1 regulates the MCC by directly interacting with the spindle assembly checkpoint protein, MAD2. WT1 colocalizes with MAD2 during mitosis and preferentially binds to the functionally active, closed-conformer, C-MAD2. Furthermore, WT1 associates with the MCC containing MAD2, BUBR1 and CDC20, resulting in prolonged inhibition of the anaphase promoting complex/cyclosome (APC/C), and delayed degradation of its substrates SECURIN and CYCLIN B1. Strikingly, RNAi-mediated depletion of WT1 leads to enhanced turnover of SECURIN, decreased lag time to anaphase, and defects in chromosome-segregation. Our findings identify WT1 as a regulator of the mitotic checkpoint and chromosomal stability. PMID:25232865

  10. The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit.

    PubMed

    Wang, Y; Hu, F; Elledge, S J

    2000-11-01

    At the end of the cell cycle, cyclin-dependent kinase (CDK) activity is inactivated to allow mitotic exit [1]. A protein phosphatase, Cdc14, plays a key role during mitotic exit in budding yeast by activating the Cdh1 component of the anaphase-promoting complex to degrade cyclin B (Clb) and inducing the CDK inhibitor Sic1 to inactivate Cdk1 [2]. To prevent mitotic exit when the cell cycle is arrested at G2/M, cells must prevent CDK inactivation. In the spindle checkpoint pathway, this is accomplished through Bfa1/Bub2, a heteromeric GTPase-activating protein (GAP) that inhibits Clb degradation by keeping the G protein Tem1 inactive [3-5]. Tem1 is required for Cdc14 activation. Here we show that in budding yeast, BUB2 and BFA1 are also required for the maintenance of G2/M arrest in response to DNA damage and to spindle misorientation. cdc13-1 bub2 and cdc13-1 bfa1 but not cdc13-1 mad2 double mutants rebud and reduplicate their DNA at the restrictive temperature. We also found that the delay in mitotic exit in mutants with misoriented spindles depended on BUB2 and BFA1, but not on MAD2. We propose that Bfa1/Bub2 checkpoint pathway functions as a universal checkpoint in G2/M that prevents CDK inactivation in response to cell-cycle delay in G2/M. PMID:11084339

  11. Interaction between Poly(ADP-ribose) and NuMA Contributes to Mitotic Spindle Pole Assembly

    E-print Network

    Coughlin, M.

    Poly(ADP-ribose) (pADPr), made by PARP-5a/tankyrase-1, localizes to the poles of mitotic spindles and is required for bipolar spindle assembly, but its molecular function in the spindle is poorly understood. To investigate ...

  12. In situ hybridization of plant meiotic and mitotic chromosomes: differences in signal detection.

    PubMed

    Clark, M S; Parker, J S

    1992-09-01

    The technique of in situ hybridization to both meiotic and mitotic chromosomes of Rumex acetosa is described. Differences in the efficiency of signal detection were observed between the two types of material. The implications of these results for in situ hybridization to other plant species are explored. PMID:1300148

  13. Uncovering immobilized trypsin digestion features from large-scale proteome data generated by high-resolution mass spectrometry.

    PubMed

    Sun, Liangliang; Zhu, Guijie; Yan, Xiaojing; Mou, Si; Dovichi, Norman J

    2014-04-11

    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, Escherichia 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-h; digestion using immobilized trypsin for 20-min produces a similar number of missed cleavages as solution-based trypsin digestion for 12-h. Third, immobilized trypsin produces quantitatively reproducible digestion of complex proteomes. Finally, there is small but measurable loss of peptide due to non-specific adsorption to the immobilization matrix. This adsorption generates a bias against detection of basic peptides. PMID:24636566

  14. vasa and piwi are required for mitotic integrity in early embryogenesis in the spider Parasteatoda tepidariorum.

    PubMed

    Schwager, Evelyn E; Meng, Yue; Extavour, Cassandra G

    2015-06-15

    Studies in vertebrate and invertebrate model organisms on the molecular basis of primordial germ cell (PGC) specification have revealed that metazoans can specify their germ line either early in development by maternally transmitted cytoplasmic factors (inheritance), or later in development by signaling factors from neighboring tissues (induction). Regardless of the mode of PGC specification, once animal germ cells are specified, they invariably express a number of highly conserved genes. These include vasa and piwi, which can play essential roles in any or all of PGC specification, development, or gametogenesis. Although the arthropods are the most speciose animal phylum, to date there have been no functional studies of conserved germ line genes in species of the most basally branching arthropod clade, the chelicerates (which includes spiders, scorpions, and horseshoe crabs). Here we present the first such study by using molecular and functional tools to examine germ line development and the roles of vasa and piwi orthologues in the common house spider Parasteatoda (formerly Achaearanea) tepidariorum. We use transcript and protein expression patterns of Pt-vasa and Pt-piwi to show that primordial germ cells (PGCs) in the spider arise during late embryogenesis. Neither Pt-vasa nor Pt-piwi gene products are localized asymmetrically to any embryonic region before PGCs emerge as paired segmental clusters in opisthosomal segments 2-6 at late germ band stages. RNA interference studies reveal that both genes are required maternally for egg laying, mitotic progression in early embryos, and embryonic survival. Our results add to the growing body of evidence that vasa and piwi can play important roles in somatic development, and provide evidence for a previously hypothesized conserved role for vasa in cell cycle progression. PMID:25257304

  15. A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission.

    PubMed Central

    Smith, M M; Yang, P; Santisteban, M S; Boone, P W; Goldstein, A T; Megee, P C

    1996-01-01

    The histone proteins are essential for the assembly and function of th e eukaryotic chromosome. Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The mutant requires two amino acid substitutions in histone H4: a lethal Thr-to-Ile change at position 82, which lies within one of the DNA-binding surfaces of the protein, and a substitution of Ala to Val at position 89 that is an intragenic suppressor. Genetic and biochemical evidence shows that the mutant histone H4 is temperature sensitive for function but not for synthesis, deposition, or stability. The chromatin structure of 2 micrometer circle minichromosomes is temperature sensitive in vivo, consistent with a defect in H4-DNA interactions. The mutant also has defects in transcription, displaying weak Spt- phenotypes. At the restrictive temperature, mutant cells arrest in the cell cycle at nuclear division, with a large bud, a single nucleus with 2C DNA content, and a short bipolar spindle. At semipermissive temperatures, the frequency of chromosome loss is elevated 60-fold in the mutant while DNA recombination frequencies are unaffected. High-copy CSE4, encoding an H3 variant related to the mammalian CENP-A kinetochore antigen, was found to suppress the temperature sensitivity of the mutant without suppressing the Spt- transcription defect. These genetic, biochemical, and phenotypic results indicate that this novel histone H4 mutant defines one or more chromatin-dependent steps in chromosome segregation. PMID:8622646

  16. Studies on the induction of mitotic gene conversion by ultraviolet irradiation. II. Action spectra.

    PubMed

    Ito, T; Kobayashi, K

    1975-10-01

    Action spectra for the induction of intragenic mitotic recombination (gene conversion) at the trp 5 locus by UV are presented for three cell stages (T0, T9 and T16) taken from synchronously growing cultures of Saccharomyces cerevisiae. The spectra over the range from 230 to 300 nm were taken mostly in 5-nm steps. The peak of action spectra was significantly shifted, regardless of the stage, toward the longer wavelengths as compared with that of the absorption spectrum of DNA (258 nm) or even that of thymine (265 nm). In one extreme case (T16), the peak was shifted 17 nm from the absorption peak of DNA. Further, the spectrum changed its shape as the cell stage advanced from non-dividing (unbudded) (T0) to a dividing phase (T16). Furthermore, the induction cross section decreased by a large factor (about 40), regardless of the wavelength, in going from T0 to T16. From observations of the high photoreversibility of induced conversions, the major primary damage was thought to be pyrimidine dimers in the DNA. One plausible explanation, though not quite satisfactory from the quantitative viewpoint for these findings was that the increasing RNA during growth would screen the incident UV differentially with respect to the stage. If this explanation is correct, thymine dimers may still be considered, in spite of the shifts and deformations in the action spectra, as the major primary damage that triggers the long series of processes leading to gene conversion. Conventional methods for obtaining action spectra are discussed in comparison with the present method, which was based on sensitivity parameter a in the proposed dose (t)-frequency (f) relation, f = (at)alpha (alpha is the multiplicity parameter). PMID:1101053

  17. Drug-induced premature chromosome condensation (PCC) protocols: cytogenetic approaches in mitotic chromosome and interphase chromatin.

    PubMed

    Gotoh, Eisuke

    2015-01-01

    Chromosome analysis is a fundamental technique which is used in wide areas of cytogenetic study including karyotyping species, hereditary diseases diagnosis, or chromosome biology study. Chromosomes are usually prepared from mitotic cells arrested by colcemid block protocol. However, obtaining mitotic chromosomes is often hampered under several circumstances. As a result, cytogenetic analysis will be sometimes difficult or even impossible in such cases. Premature chromosome condensation (PCC) (see Note 1) is an alternative method that has proved to be a unique and useful way in chromosome analysis. Former, PCC has been achieved following cell fusion method (cell-fusion PCC) mediated either by fusogenic viruses (e.g., Sendai virus) or cell fusion chemicals (e.g., polyethylene glycol), but the cell fusion PCC has several drawbacks. The novel drug-induced PCC using protein phosphatase inhibitors was introduced about 20 years ago. This method is much simpler and easier even than the conventional mitotic chromosome preparation protocol use with colcemid block and furthermore obtained PCC index (equivalent to mitotic index for metaphase chromosome) is usually much higher than colcemid block method. Moreover, this method allows the interphase chromatin to be condensed to visualize like mitotic chromosomes. Therefore drug-induced PCC has opened the way for chromosome analysis not only in metaphase chromosomes but also in interphase chromatin. The drug-induced PCC has thus proven the usefulness in cytogenetics and other cell biology fields. For this second edition version, updated modifications/changes are supplemented in Subheadings 2, 3, and 4, and a new section describing the application of PCC in chromosome science fields is added with citation of updated references. PMID:25827875

  18. Functional Characterization of G12, a Gene Required for Mitotic Progression during Gastrulation in Zebrafish

    NASA Technical Reports Server (NTRS)

    Reinsch, Sigrid; Conway, Gregory; Dalton, Bonnie P. (Technical Monitor)

    2002-01-01

    In a differential RNA display screen we have isolated a zebrafish gene, G12, for which homologs can only be found in DNA databases for vertebrates, but not invertebrates. This suggests that this is a gene required specifically in vertebrates. G12 expression is upregulated at mid-blastula transition (MBT). Morpholino inactivation of this gene by injection into 1-cell embryos results in mitotic defects and apoptosis shortly after MBT. Nuclei in morpholino treated embryos also display segregation defects. We have characterized the localization of this gene as a GFP fusion in live and fixed embryos. Overexpression of G12-GFP is non-toxic. Animals retain GFP expression for at least 7 days with no developmental defects, Interestingly in these animals G12-GFP is never detectable in blood cells though blood is present. In the deep cells of early embryos, G 12GFP is localized to nuclei and cytoskeletal elements in interphase and to the centrosome and spindle apparatus during mitosis. In the EVL, G12-GFP shows additional localization to the cell periphery, especially in mitosis. In the yolk syncytium, G12-GFP again localizes to nuclei and strongly to cytoplasmic microtubules of migrating nuclei at the YSL margin. Morpholinc, injection specifically into the YSL after cellularization blocks epiboly and nuclei of the YSL show mitotic defects while deep cells show no mitotic defects and continue to divide. Rescue experiments in which morpholino and G12-GFP RNA are co-injected indicate partial rescue by the G12-GFP. The rescue is cell autonomous; that is, regions of the embryo with higher G12-GFP expression show fewer mitotic defects. Spot 14, the human bomolog of G12, has been shown to be amplified in aggressive breast tumors. This finding, along with our functional and morphological data suggest that G12 and spot 14 are vertebrate-specific and may function either as mitotic checkpoints or as structural components of the spindle apparatus.

  19. Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition.

    PubMed

    Yuan, Kai; O'Farrell, Patrick H

    2015-03-16

    The timing mechanism for mitotic progression is still poorly understood. The spindle assembly checkpoint (SAC), whose reversal upon chromosome alignment is thought to time anaphase [1-3], is functional during the rapid mitotic cycles of the Drosophila embryo; but its genetic inactivation had no consequence on the timing of the early mitoses. Mitotic cyclins-Cyclin A, Cyclin B, and Cyclin B3-influence mitotic progression and are degraded in a stereotyped sequence [4-11]. RNAi knockdown of Cyclins A and B resulted in a Cyclin B3-only mitosis in which anaphase initiated prior to chromosome alignment. Furthermore, in such a Cyclin B3-only mitosis, colchicine-induced SAC activation failed to block Cyclin B3 destruction, chromosome decondensation, or nuclear membrane re-assembly. Injection of Cyclin B proteins restored the ability of SAC to prevent Cyclin B3 destruction. Thus, SAC function depends on particular cyclin types. Changing Cyclin B3 levels showed that it accelerated progress to anaphase, even in the absence of SAC function. The impact of Cyclin B3 on anaphase initiation appeared to decline with developmental progress. Our results show that different cyclin types affect anaphase timing differently in the early embryonic divisions. The early-destroyed cyclins-Cyclins A and B-restrain anaphase-promoting complex/cyclosome (APC/C) function, whereas the late-destroyed cyclin, Cyclin B3, stimulates function. We propose that the destruction schedule of cyclin types guides mitotic exit by affecting both Cdk1 and APC/C, whose activities change as each cyclin type is lost. PMID:25754637

  20. Computer-aided diagnosis for phase-contrast X-ray computed tomography: quantitative characterization of human patellar cartilage with high-dimensional geometric features.

    PubMed

    Nagarajan, Mahesh B; Coan, Paola; Huber, Markus B; Diemoz, Paul C; Glaser, Christian; Wismüller, Axel

    2014-02-01

    Phase-contrast computed tomography (PCI-CT) has shown tremendous potential as an imaging modality for visualizing human cartilage with high spatial resolution. Previous studies have demonstrated the ability of PCI-CT to visualize (1) structural details of the human patellar cartilage matrix and (2) changes to chondrocyte organization induced by osteoarthritis. This study investigates the use of high-dimensional geometric features in characterizing such chondrocyte patterns in the presence or absence of osteoarthritic damage. Geometrical features derived from the scaling index method (SIM) and statistical features derived from gray-level co-occurrence matrices were extracted from 842 regions of interest (ROI) annotated on PCI-CT images of ex vivo human patellar cartilage specimens. These features were subsequently used in a machine learning task with support vector regression to classify ROIs as healthy or osteoarthritic; classification performance was evaluated using the area under the receiver-operating characteristic curve (AUC). SIM-derived geometrical features exhibited the best classification performance (AUC, 0.95?±?0.06) and were most robust to changes in ROI size. These results suggest that such geometrical features can provide a detailed characterization of the chondrocyte organization in the cartilage matrix in an automated and non-subjective manner, while also enabling classification of cartilage as healthy or osteoarthritic with high accuracy. Such features could potentially serve as imaging markers for evaluating osteoarthritis progression and its response to different therapeutic intervention strategies. PMID:24043594

  1. Studies of mitotic and centromeric abnormalities in Roberts syndrome: Implications for a defect in the mitotic mechanism

    Microsoft Academic Search

    Ethylin Wang Jabs; Cathy M. Tuck-Muller; Ronald Cusano; J. B. Rattner

    1991-01-01

    Roberts syndrome is an inherited human condition that is of particular interest because separation of centromeres and constitutive heterochromatin is observed in metaphase chromosomes. In this study we investigated the frequency of other cytological abnormalities in three Roberts syndrome patients. Our findings when taken with previous cytological reports emphasize that there are other features that are equally characteristic of Roberts

  2. Lip-Reading Aids Word Recognition Most in Moderate Noise: A Bayesian Explanation Using High-Dimensional Feature Space

    PubMed Central

    Ross, Lars A.; Foxe, John J.; Parra, Lucas C.

    2009-01-01

    Watching a speaker's facial movements can dramatically enhance our ability to comprehend words, especially in noisy environments. From a general doctrine of combining information from different sensory modalities (the principle of inverse effectiveness), one would expect that the visual signals would be most effective at the highest levels of auditory noise. In contrast, we find, in accord with a recent paper, that visual information improves performance more at intermediate levels of auditory noise than at the highest levels, and we show that a novel visual stimulus containing only temporal information does the same. We present a Bayesian model of optimal cue integration that can explain these conflicts. In this model, words are regarded as points in a multidimensional space and word recognition is a probabilistic inference process. When the dimensionality of the feature space is low, the Bayesian model predicts inverse effectiveness; when the dimensionality is high, the enhancement is maximal at intermediate auditory noise levels. When the auditory and visual stimuli differ slightly in high noise, the model makes a counterintuitive prediction: as sound quality increases, the proportion of reported words corresponding to the visual stimulus should first increase and then decrease. We confirm this prediction in a behavioral experiment. We conclude that auditory-visual speech perception obeys the same notion of optimality previously observed only for simple multisensory stimuli. PMID:19259259

  3. Temporal bone histopathological features of a worker who received high doses of radiation in a criticality accident: a case report.

    PubMed

    Kaga, Kimitaka; Maeshima, Arafumi; Tsuzuku, Toshihiro; Kondo, Kenji; Morizono, Tetsuo

    2011-04-01

    In 1999, three workers received high doses of radiation in a small Japanese plant while they were preparing fuel for an experimental reactor. This criticality accident at melting point was caused by the addition of too much uranium enriched to a relatively high level, causing a 'criticality' (a limited uncontrolled nuclear chain reaction), which continued intermittently for 20 h. The three workers concerned were hospitalized, two in a critical condition. The first worker died 12 weeks later, and the second worker 7 months later. The third worker is in a healthy condition. We report on the temporal bone histopathological features of the second worker. Our temporal bone study revealed: 1) the large loss of bone marrow tissue with a small number of myelocytes remaining in the mastoid bone and the abundance of fatty tissue in the mastoid bone, 2) inflammation of the mucosal layer of the middle ear and the mastoid air cells, 3) mild degeneration of the spiral ganglions and the sensory hair cells of the cochlea, 4) mild degenerative changes of sensory hair cells of the semicircular canals and otolith organs, and 5) vestibular ganglions and geniculate ganglions were well preserved. PMID:21162658

  4. 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.

  5. Geophysical investigations of the Southeast Tyrrhenian Sea (Italy): volcanic features of the Palinuro Seamount enhanced by high resolution DTM

    NASA Astrophysics Data System (ADS)

    Passaro, S.; Milano, G.; Sprovieri, M.; Marsella, E.; Ruggieri, S.

    2009-04-01

    The Palinuro Seamount is a volcanic edifice located in the southeastern Tyrrhenian Sea, the small extensional back-arc basin in the Central Mediterranean Sea. Although several geophysical studies have been performed in the Tyrrhenian Sea, the Palinuro Seamount has not yet been subjected to intensive geophysical exploration, despite its global extension, thus representing the less known Seamount of the area. Previous studies on this Seamount focused on volcanic products, magnetic profiles, single beam data and, recentely, multibeam swath batimetry describing, the latter two, the general physiographic asset of the volcanic complex. On November 2007, a geophysical survey was performed by IAMC-CNR research institute (Naples, Italy) in the southeastern Tyrrhenian Sea within the "Aeolian_2007" cruise onboard the Urania oceanographic vessel. During the second Leg of the survey, detailed multibeam data acquisition was carried out in order to obtain high resolution DTM of the major Seamounts in the study area. Here we report a new, very high resolution Digital Terrain Model (DTM) of the Palinuro Seamount, resulting by multibeam swath bathymetric data. More than 1.000 squared Km of new high resolution multibeam sonar data have been processed and interpreted from IAMC - CNR of Naples. The processed bathymetric data of the seamount cover a depth range -3200 / -84 meters and unreported topographic features were detected both below 1000 m in depth and at the summit. The DEM evidences a global extension larger than that expected, characterized by a roughly elliptical shape extending about 55 km along E-W and 25 km in the N-S direction. The morphology reveals a very articulated summit consisting in a group of overlapped and/or coalescent volcanic cones inside collapsed calderas. Relic domes of calderic collapses are identifiable both in the western and in the central sectors of the Palinuro Seamount.

  6. Coordinated Observations of Aeolian Features from the Mars Exploration Rovers (MER) and the Mars Express High Resolution Stereo Camera and Other Orbiters

    NASA Technical Reports Server (NTRS)

    Greeley, R.; Thompson, S. D.; Whelley, P. L.; Squyres, S.; Neukum, G.; Arvidson, R.; Malin, M.; Kuzmin, R.; Christensen, P.; Rafkin, S.

    2004-01-01

    Surface features associated with aeolian (wind) processes at the Mars Exploration Rover (MER) landing sites for Spirit (Gusev crater) and Opportunity (Sinus Meridiani) were observed from the surface and from orbit through coordinated observations by the rovers and the Mars Express orbiter High Resolution Stereo Camera and compared with features seen in other orbiter data and with wind vectors predicted by a numerical mesoscale model of the atmosphere.

  7. Unequal mitotic sister chromatid exchange: A rare mechanism for chromosomal abnormality resulting in duplication/deletion of chromosome 7q

    SciTech Connect

    Eydoux, P.; Ortenberg, J.; Chalifoux, N. [Montreal Children`s Hospital, Quebec (Canada)

    1994-09-01

    We report a case of unequal mitotic chromatid exchange, which has rarely been reported as a mechanism for microscopic chromosomal anomalies. The proposita was born at 40 weeks, after an uneventful pregnancy, of parents with a negative family history. The baby was small for gestational age and had dysmorphic features, including scaphocephaly, bilateral epicanthal folds and palpebral ptosis, mild hypertelorism, hypoplasia of orbital contours, right coloboma, bulbous prominent nose, retrognathism, downturned mouth, low set posteriorly rotated ears, tapering of the limbs. bilateral Sydney creases. At 5 months, she was under the 5th percentile for height, weight and head circumference, and had a mild developmental delay. The karyotype showed an abnormality of chromosome 7 in all cells, half with a duplication and half with a deletion of the same region; 46,XX,del(7)(q33{yields}q34)/46,XX,dup(7)(q33{yields}q34). This chromosomal abnormality could be explained by an unequal chromatid exchange occuring in the first mitosis of the embryo. To our knowledge, only one such human microscopic abnormality, involving chromosome Y, has been reported to date. This type of genetic unbalance could be missed by molecular techniques.

  8. The rejection of noncellular artifacts in Papanicolaou-stained slide specimens by an automated high-resolution system. Identification of important cytometric features.

    PubMed

    Dytch, H E; Bartels, P H; Bibbo, M; Pishotta, F T; Wied, G L

    1983-12-01

    The important cytodiagnostic features that permit discrimination of typical cell types by high-resolution image analysis and pattern recognition techniques have been previously studied in detail. An automated system for the diagnosis of Papanicolaou-stained specimens must also deal, however, with the "real world" of extraneous noncellular artifacts and debris found on every slide. Features that are ideal for the separation of typical normal and abnormal cells may not be adequate by themselves to reject these objects. A new set of discriminatory features must be found. In order to identify those features, a large set of images acquired using the TICAS high-resolution television rapid-scanning system was analyzed and studied. These images, from a variety of slide types, included normal cells, abnormal cells and noncellular artifacts identified by low-resolution preprocessing logic as suspicious enough to warrant high-resolution study. The results indicate that the more important features for such discrimination are not those traditionally important in distinguishing abnormal from normal cells but include color relations, shape measures, boundary properties and texture features. PMID:6670792

  9. Virus Replication, Cytopathology, and Lysosomal Enzyme Response of Mitotic and Interphase Hep-2 Cells Infected with Poliovirus

    PubMed Central

    Bienz, Kurt; Egger, Denise; Wolff, David A.

    1973-01-01

    Mitotic Hep-2 cells, selected by the PEL (colloidal silica) density gradient method and held in mitosis with Colcemid, are readily infected by poliovirus type I (Mahoney). They produce and release the same amount of virus as interphase, random-growing cells. In contrast to interphase cells, mitotic cells show no detectable virus-induced cytopathic effect at the light microscopy level and only slight alterations, consisting of small clusters of vacuoles, at the electron microscopy level. Mitotic cells contain the same total amount of lysosomal enzymes per cell as interphase cells, but they display no redistribution of lysosomal enzymes during the virus infection as interphase cells do. This supports the view that lysosomal enzyme redistribution is associated with the cytopathic effect in poliovirus infection but shows that virus synthesis and release is not dependent on either the cytopathic effect or lysosomal enzyme release. The possible reasons for the lack of cytopathic effect in mitotic cells are discussed. Images PMID:4121707

  10. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

    SciTech Connect

    Yu, Yueyang [Division of Infectious Diseases, Brigham and Women's Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)] [Division of Infectious Diseases, Brigham and Women's Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women's Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)] [Division of Infectious Diseases, Brigham and Women's Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

  11. Draft Genome Sequences of Supercritical CO[subscript 2]-Tolerant Bacteria Bacillus subterraneus MITOT1 and Bacillus cereus MIT0214

    E-print Network

    Peet, Kyle Creighton

    We report draft genome sequences of Bacillus subterraneus MITOT1 and Bacillus cereus MIT0214 isolated through enrichment of samples from geologic sequestration sites in pressurized bioreactors containing a supercritical ...

  12. Nucleocytoplasmic transport in the midzone membrane domain controls yeast mitotic spindle disassembly.

    PubMed

    Lucena, Rafael; Dephoure, Noah; Gygi, Steve P; Kellogg, Douglas R; Tallada, Victor A; Daga, Rafael R; Jimenez, Juan

    2015-05-11

    During each cell cycle, the mitotic spindle is efficiently assembled to achieve chromosome segregation and then rapidly disassembled as cells enter cytokinesis. Although much has been learned about assembly, how spindles disassemble at the end of mitosis remains unclear. Here we demonstrate that nucleocytoplasmic transport at the membrane domain surrounding the mitotic spindle midzone, here named the midzone membrane domain (MMD), is essential for spindle disassembly in Schizosaccharomyces pombe cells. We show that, during anaphase B, Imp1-mediated transport of the AAA-ATPase Cdc48 protein at the MMD allows this disassembly factor to localize at the spindle midzone, thereby promoting spindle midzone dissolution. Our findings illustrate how a separate membrane compartment supports spindle disassembly in the closed mitosis of fission yeast. PMID:25963819

  13. Synergy between Multiple Microtubule-Generating Pathways Confers Robustness to Centrosome-Driven Mitotic Spindle Formation

    PubMed Central

    Hayward, Daniel; Metz, Jeremy; Pellacani, Claudia; Wakefield, James G.

    2014-01-01

    Summary The mitotic spindle is defined by its organized, bipolar mass of microtubules, which drive chromosome alignment and segregation. Although different cells have been shown to use different molecular pathways to generate the microtubules required for spindle formation, how these pathways are coordinated within a single cell is poorly understood. We have tested the limits within which the Drosophila embryonic spindle forms, disrupting the inherent temporal control that overlays mitotic microtubule generation, interfering with the molecular mechanism that generates new microtubules from preexisting ones, and disrupting the spatial relationship between microtubule nucleation and the usually dominant centrosome. Our work uncovers the possible routes to spindle formation in embryos and establishes the central role of Augmin in all microtubule-generating pathways. It also demonstrates that the contributions of each pathway to spindle formation are integrated, highlighting the remarkable flexibility with which cells can respond to perturbations that limit their capacity to generate microtubules. PMID:24389063

  14. Preparative in situ hybridization: selection of chromosome region-specific libraries on mitotic chromosomes.

    PubMed

    Hozier, J; Graham, R; Westfall, T; Siebert, P; Davis, L

    1994-02-01

    We have developed preparative in situ hybridization (Prep-ISH) of complex DNA populations to mitotic chromosomes as a means of generating chromosome region-specific DNA subpopulations. Prep-ISH is a combination of two cytogenetic techniques: in situ hybridization of DNA molecules to mitotic chromosomes and chromosome microdissection. Here, we present test cases demonstrating the feasibility of this approach on mouse and human genomes, using single nuclei, single chromosomes, or single chromosomal subregions to assess sensitivity, specificity, and representation of the Prep-ISH technique. Prep-ISH has a number of applications in studies of gene expression and genome organization, including efficient cytogenetic sorting of tissue-specific cDNAs and genomic DNA libraries. In addition, Prep-ISH is likely to dramatically reduce the number of candidate genes to aid in gene discovery efforts and to improve efficiency of developing transcription maps and YAC and cosmid contigs through defined cytogenetic regions. PMID:8188286

  15. Spatio-temporal Model for Silencing of the Mitotic Spindle Assembly Checkpoint

    PubMed Central

    Chen, Jing; Liu, Jian

    2014-01-01

    The spindle assembly checkpoint arrests mitotic progression until each kinetochore secures a stable attachment to the spindle. Despite fluctuating noise, this checkpoint remains robust and remarkably sensitive to even a single unattached kinetochore among many attached kinetochores; moreover, the checkpoint is silenced only after the final kinetochore-spindle attachment. Experimental observations have shown that checkpoint components stream from attached kinetochores along microtubules toward spindle poles. Here, we incorporate this streaming behavior into a theoretical model that accounts for the robustness of checkpoint silencing. Poleward streams are integrated at spindle poles, but are diverted by any unattached kinetochore; consequently, accumulation of checkpoint components at spindle poles increases markedly only when every kinetochore is properly attached. This step-change robustly triggers checkpoint silencing after, and only after, the final kinetochore-spindle attachment. Our model offers a conceptual framework that highlights the role of spatiotemporal regulation in mitotic spindle checkpoint signaling and fidelity of chromosome segregation. PMID:25216458

  16. C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis

    Microsoft Academic Search

    Kirsten A. Hagstrom; Victor F. Holmes; Nicholas R. Cozzarelli; Barbara J. Meyer

    2002-01-01

    Chromosome segregation and X-chromosome gene regulation in Caenorhabditis elegans share the component MIX-1, a mitotic protein that also represses X-linked genes during dosage compensation. MIX-1 achieves its dual roles through interactions with different protein partners. To repress gene expression, MIX-1 acts in an X-chromosome complex that resembles the mitotic condensin complex yet lacks chromosome segregation function. Here we show that

  17. EBP2 Plays a Key Role in Epstein-Barr Virus Mitotic Segregation and Is Regulated by Aurora Family Kinases

    Microsoft Academic Search

    Priya Kapoor; Brigitte D. Lavoie; Lori Frappier

    2005-01-01

    Epstein-Barr virus (EBV) genomes persist indefinitely in latently infected human cells, in part due to their ability to stably segregate during cell division. This process is mediated by the viral EBNA1 protein, which tethers the viral episomes to the cellular mitotic chromosomes. We have previously identified a mitotic chromosomal protein, human EBNA1 binding protein 2 (hEBP2), which binds to EBNA1

  18. The role of Saccharomyces cerevisiae Cdc40p in DNA replication and mitotic spindle formation and\\/or maintenance

    Microsoft Academic Search

    Nora Vaisman; Andrey Tsouladze; Kenneth Robzyk; Sigal Ben-Yehuda; Martin Kupiec; Yona Kassir

    1995-01-01

    Successful progression through the cell cycle requires the coupling of mitotic spindle formation to DNA replication. In this report we present evidence suggesting that, inSaccharomyces cerevisiae, theCDC40 gene product is required to regulate both DNA replication and mitotic spindle formation. The deduced amino acid sequence ofCDC40 (455 amino acids) contains four copies of a ß-transducin-like repeat. Cdc40p is essential only

  19. CCAAT\\/enhancer-binding protein is required for mitotic clonal expansion during adipogenesis

    Microsoft Academic Search

    Qi-Qun Tang; Tamara C. Otto

    2003-01-01

    Hormonal induction of growth-arrested 3T3-L1 preadipocytes triggers a signaling cascade that culminates in adipogenesis. CCAAT\\/enhancer-binding protein (C\\/EBP) is expressed immediately but gains DNA-binding activity only after a long lag as the cells synchronously begin mitotic clonal expansion (MCE). After MCE, a process required for adipogenesis, C\\/EBP activates expression of C\\/EBP and peroxisome proliferator-activated receptor , which then transcriptionally activate genes

  20. Differential staining and chromatin packing of the mitotic chromosomes of the newt Triturus cristatus

    Microsoft Academic Search

    Edwina Rudak; H. G. Callan

    1976-01-01

    Mitotic metaphase chromosomes of cold-treated Triturus cristatus show a characteristic pattern of constrictions, most of which lie close, though not immediately adjacent, to the centromeres. The chromatin in these cold-induced constrictions stains intensely with Giemsa. Cold-treated spermatogonia show spiral structure throughout the metaphase chromatids; the packing of chromatin fibrils is much tighter in the constricted regions than elsewhere, and the

  1. Aurora kinase inhibitors: a new class of drugs targeting the regulatory mitotic system

    Microsoft Academic Search

    José Alejandro Pérez Fidalgo; Desamparados Roda; Susana Roselló; Edith Rodríguez-Braun; Andrés Cervantes

    2009-01-01

    The present review gives a perspective on the Aurora kinase family members, their function in normal cells, their role in\\u000a cancer progression as well as their potential as target for anticancer treatment. Mitosis has been an important target for\\u000a anticancer therapy development, leading to some specific drugs mainly addressing Tubulines, as a key structure of the mitotic\\u000a spindle. Vinca alkaloids,

  2. Mitotic recombination in Candida albicans : Recessive lethal alleles linked to a gene required for methionine biosynthesis

    Microsoft Academic Search

    William L. Whelan; David R. Soll

    1982-01-01

    Genetic analysis by ultraviolet-induced mitotic segregation indicated that Candida albicans wild-type strain Ca526 was heterozygous at a gene (MET) required for biosynthesis of methionine. The MET gene was shown to be linked to two other genes (LET1, LET2) whose recessive alleles (let1, let2) each determined lethality when homozygous. The phenotype determined by let1 was temperaturesensitive. The inferred genotype of strain

  3. Caspase-Mediated Specific Cleavage of BubR1 Is a Determinant of Mitotic Progression

    Microsoft Academic Search

    Mijin Kim; Katie Murphy; Fang Liu; Sharon E. Parker; Melissa L. Dowling; Wesley Baff; Gary D. Kao

    2005-01-01

    The fidelity of chromosomal duplication is monitored by cell cycle checkpoints operational during mitosis. One such cell cycle delay is invoked by microtubule-targeting agents such as nocodazole or paclitaxel (Taxol) and is mediated by mitotic checkpoint proteins that include BubR1. Relatively little is known about the regulation of expression and stability of BubR1 (or other checkpoint proteins) and how these

  4. Mitotic Golgi is in a Dynamic Equilibrium Between Clustered and Free Vesicles Independent of the ER

    Microsoft Academic Search

    Stephen A. Jesch; Amy J. Mehta; Meel Velliste; Robert F. Murphy; Adam D. Linstedt

    2001-01-01

    Golgi inheritance during cell division involves Golgi dis-assembly but it remains unclear whether the break-down product is dispersed vesicles, clusters of vesicles or a fused ER\\/Golgi network. Evidence against the fused ER\\/Golgi hypothesis was previously obtained from subcellular fractionation studies, but left con-cerns about the means used to obtain and disrupt mi-totic cells. Here, we performed velocity gradient analy-sis on

  5. Mitotic and polytene chromosomes analysis of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae)

    Microsoft Academic Search

    Antigone ZacharopoulouAntonios; Antonios A. Augustinos; Waheed A. A. SayedAlan; Alan S. Robinson; Gerald Franz

    2011-01-01

    The Oriental fruit fly, Batrocera dorsalis s.s. (Hendel) is one of the most destructive agricultural pests, belonging to a large group of difficult to distinguish morphologically\\u000a species, referred as the B. dorsalis complex. We report here a cytogenetic analysis of two laboratory strains of the species and provide a photographic polytene\\u000a chromosome map from larval salivary glands. The mitotic complement

  6. Mitotic Kinesin-Like Protein 2 Binds and Colocalizes with Papillomavirus E2 during Mitosis

    Microsoft Academic Search

    Ting Yu; Yu-Cai Peng; Elliot J. Androphy

    2007-01-01

    MKlp2 is a kinesin-like motor protein of the central mitotic spindle required for completion of cytokinesis. Papillomavirus E2 is a sequence specific DNA binding protein that regulates viral transcription and replica- tion and is responsible for partitioning viral episomes into daughter cells during cell division. We demonstrate that MKlp2 specifically associates with the E2 protein during mitosis. Using chromatin immunoprecipitation,

  7. Exit from Arsenite-Induced Mitotic Arrest Is p53 Dependent

    PubMed Central

    McNeely, Samuel C.; Xu, Xiaogiang; Taylor, B. Frazier; Zacharias, Wolfgang; McCabe, Michael J.; States, J. Christopher

    2006-01-01

    Background Arsenic is both a human carcinogen and a chemotherapeutic agent, but the mechanism of neither arsenic-induced carcinogenesis nor tumor selective cytotoxicity is clear. Using a model cell line in which p53 expression is regulated exogenously in a tetracycline-off system (TR9-7 cells), our laboratory has shown that arsenite disrupts mitosis and that p53-deficient cells [p53(?)], in contrast to p53-expressing cells [p53(+)], display greater sensitivity to arsenite-induced mitotic arrest and apoptosis. Objective Our goal was to examine the role p53 plays in protecting cells from arsenite-induced mitotic arrest. Methods p53(+) and p53(?) cells were synchronized in G2 phase using Hoechst 33342 and released from synchrony in the presence or absence of 5 ?M sodium arsenite. Results Mitotic index analysis demonstrated that arsenite treatment delayed exit from G2 in p53(+) and p53(?) cells. Arsenite-treated p53(+) cells exited mitosis normally, whereas p53(?) cells exited mitosis with delayed kinetics. Microarray analysis performed on mRNAs of cells exposed to arsenite for 0 and 3 hr after release from G2 phase synchrony showed that arsenite induced inhibitor of DNA binding-1 (ID1) differentially in p53(+)and p53(?) cells. Immunoblotting con-firmed that ID1 induction was more extensive and sustained in p53(+) cells. Conclusions p53 promotes mitotic exit and leads to more extensive ID1 induction by arsenite. ID1 is a dominant negative inhibitor of transcription that represses cell cycle regulatory genes and is elevated in many tumors. ID1 may play a role in the survival of arsenite-treated p53(+) cells and contribute to arsenic carcinogenicity. PMID:16966095

  8. Structural differentiation of the meiotic and mitotic chromosomes of the salamander, Ambystoma macrodactylum

    Microsoft Academic Search

    James Kezer; Pedro E. León

    1980-01-01

    The lampbrush chromosomes of the long-toed salamander, Ambystoma macrodactylum Baird, have been analysed and a map of the oocyte genome prepared. The location of C-bands and cold-induced-constrictions has been established in mitotic chromosomes and compared with the location of marker structures and chiasmata in several lampbrush bivalents. In the lampbrush chromosomes, C-bands are tentatively correlated with sphere-organizing loci and with

  9. An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic golgi fragments

    Microsoft Academic Search

    Catherine Rabouille; Timothy P Levine; Jan-Michael Peters; Graham Warren

    1995-01-01

    Golgi cisternae regrew in a cell-free system from mitotic Golgi fragments incubated with buffer alone. Pretreatment with NEM or salt washing inhibited regrowth, but this could be restored either by p97, an NSF-like ATPase, or by NSF together with SNAPs and p115, a vesicle docking protein. The morphology of cisternae regrown with p97 and NSF-SNAPs-p115 differed, suggesting that they play

  10. Effects of Latanoprost on Tyrosinase Activity and Mitotic Index of Cultured Melanoma Lines

    Microsoft Academic Search

    Radoslaw Dutkiewicz; Daniel M Albert; Leonard A Levin

    2000-01-01

    The intraocular pressure-lowering drug latanoprost, a phenyl-substituted analogue of prostaglandin F2?(PGF2?), increases iris pigmentation in a small number of patients. In theory, this could be due to increased melanogenesis or melanocyte proliferation. To distinguish these two possibilities, the present study examined the effects of latanoprost on tyrosinase activity (the rate-limiting step for melanin synthesis) and mitotic index of cultured melanoma

  11. Effects of latanoprost on tyrosinase activity and mitotic index of cultured melanoma lines.

    PubMed

    Dutkiewicz, R; Albert, D M; Levin, L A

    2000-05-01

    The intraocular pressure-lowering drug latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha (PGF2 alpha), increases iris pigmentation in a small number of patients. In theory, this could be due to increased melanogenesis or melanocyte proliferation. To distinguish these two possibilities, the present study examined the effects of latanoprost on tyrosinase activity (the rate-limiting step for melanin synthesis) and mitotic index of cultured melanoma lines. Murine cutaneous melanoma lines (S91 and B16), and human uveal (OCM1, OCM3, and OM431) and cutaneous (SK-MEL5 and M21) melanoma lines were cultured with PGE1, PGE2, PGF2 alpha, latanoprost, or the adenylate cyclase stimulating agent forskolin. After treatment, tyrosinase was assayed with respect to its dopa oxidase activity using a colorimetric assay. PGE1, PGE2, PGF2 alpha, and latanoprost greatly increased tyrosinase activity in murine melanoma lines and caused small increases in tyrosinase activity in human uveal and cutaneous melanoma lines. Similar results were obtained with the cAMP-elevating compound forskolin. Cyclic AMP content, as determined by an enzyme-linked immunoassay, was similarly increased by all treatments, with forskolin being the most potent stimulator. Since the species difference in tyrosinase activity was observed without an apparent difference in induction of cAMP, latanoprost would appear to induce tyrosinase activity through a non-cAMP-dependent pathway. Finally, latanoprost and PGF2 alpha did not enhance the mitotic index of human uveal or cutaneous melanoma lines, measured by [6-3H] thymidine uptake, although they increased the mitotic index of one murine cutaneous line. Given that latanoprost induced tyrosinase activity, but did not increase the mitotic index in any of the human melanoma lines studied, this suggests that the in vivo iris pigmentation side effect of latanoprost may not result from increased cell division, but from elevated tyrosinase activity. PMID:10870514

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

    PubMed Central

    Lipavská, Helena; Mašková, Petra; Vojvodová, Petra

    2011-01-01

    Background During the last three decades, the cell cycle and its control by cyclin-dependent kinases (CDKs) have been extensively studied in eukaryotes. This endeavour has produced an overall picture that basic mechanisms seem to be largely conserved among all eukaryotes. The intricate regulation of CDK activities includes, among others, CDK activation by CDC25 phosphatase at G2/M. In plants, however, studies of this regulation have lagged behind as a plant Cdc25 homologue or other unrelated phosphatase active at G2/M have not yet been identified. Scope Failure to identify a plant mitotic CDK activatory phosphatase led to characterization of the effects of alien cdc25 gene expression in plants. Tobacco, expressing the Schizosaccharomyces pombe mitotic activator gene, Spcdc25, exhibited morphological, developmental and biochemical changes when compared with wild type (WT) and, importantly, increased CDK dephosphorylation at G2/M. Besides changes in leaf shape, internode length and root development, in day-neutral tobacco there was dramatically earlier onset of flowering with a disturbed acropetal floral capacity gradient typical of WT. In vitro, de novo organ formation revealed substantially earlier and more abundant formation of shoot primordia on Spcdc25 tobacco stem segments grown on shoot-inducing media when compared with WT. Moreover, in contrast to WT, stem segments from transgenic plants formed shoots even without application of exogenous growth regulator. Spcdc25-expressing BY-2 cells exhibited a reduced mitotic cell size due to a shortening of the G2 phase together with high activity of cyclin-dependent kinase, NtCDKB1, in early S-phase, S/G2 and early M-phase. Spcdc25-expressing tobacco (‘Samsun’) cell suspension cultures showed a clustered, more circular, cell phenotype compared with chains of elongated WT cells, and increased content of starch and soluble sugars. Taken together, Spcdc25 expression had cytokinin-like effects on the characteristics studied, although determination of endogenous cytokinin levels revealed a dramatic decrease in Spcdc25 transgenics. Conclusions The data gained using the plants expressing yeast mitotic activator, Spcdc25, clearly argue for the existence and importance of activatory dephosphorylation at G2/M transition and its interaction with cytokinin signalling in plants. The observed cytokinin-like effects of Spcdc25 expression are consistent with the concept of interaction between cell cycle regulators and phytohormones during plant development. The G2/M control of the plant cell cycle, however, remains an elusive issue as doubts persist about the mode of activatory dephosphorylation, which in other eukaryotes is provided by Cdc25 phosphatase serving as a final all-or-nothing mitosis regulator. PMID:21339187

  13. Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas

    PubMed Central

    Kim, Il-Jin; Quigley, David; To, Minh D.; Pham, Patrick; Lin, Kevin; Jo, Brian; Jen, Kuang-Yu; Raz, Dan; Kim, Jae; Mao, Jian-Hua; Jablons, David; Balmain, Allan

    2015-01-01

    Analysis of gene expression patterns in normal tissues and their perturbations in tumors can help to identify the functional roles of oncogenes or tumor suppressors and identify potential new therapeutic targets. Here, gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. The networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. Differential correlation analysis shows that the NKX2-1 network in tumors includes pathways associated with glutamate metabolism, and identifies Vaccinia-related kinase (VRK1) as a potential drug target in a tumor-specific mitotic network. We show that VRK1 inhibition cooperates with inhibition of PARP signaling to inhibit growth of lung tumor cells. Targeting of genes that are recruited into tumor mitotic networks may provide a wider therapeutic window than that seen by inhibition of known mitotic genes. PMID:23591868

  14. Kif18a is specifically required for mitotic progression during germ line development.

    PubMed

    Czechanski, Anne; Kim, Haein; Byers, Candice; Greenstein, Ian; Stumpff, Jason; Reinholdt, Laura G

    2015-06-15

    Genome integrity in the developing germ line is strictly required for fecundity. In proliferating somatic cells and in germ cells, there are mitotic checkpoint mechanisms that ensure accurate chromosome segregation and euploidy. There is growing evidence of mitotic cell cycle components that are uniquely required in the germ line to ensure genome integrity. We previously showed that the primary phenotype of germ cell deficient 2 (gcd2) mutant mice is infertility due to germ cell depletion during embryogenesis. Here we show that the underlying mutation is a mis-sense mutation, R308K, in the motor domain of the kinesin-8 family member, KIF18A, a protein that is expressed in a variety of proliferative tissues and is a key regulator of chromosome alignment during mitosis. Despite the conservative nature of the mutation, we show that its functional consequences are equivalent to KIF18A deficiency in HeLa cells. We also show that somatic cells progress through mitosis, despite having chromosome alignment defects, while germ cells with similar chromosome alignment defects undergo mitotic arrest and apoptosis. Our data provide evidence for differential requirements for chromosome alignment in germ and somatic cells and show that Kif18a is one of a growing number of genes that are specifically required for cell cycle progression in proliferating germ cells. PMID:25824710

  15. Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway

    PubMed Central

    Li, Wenyan; Wu, Jingfang; Yang, Jianming; Sun, Shan; Chai, Renjie; Chen, Zheng-Yi; Li, Huawei

    2015-01-01

    The activation of cochlear progenitor cells is a promising approach for hair cell (HC) regeneration and hearing recovery. The mechanisms underlying the initiation of proliferation of postnatal cochlear progenitor cells and their transdifferentiation to HCs remain to be determined. We show that Notch inhibition initiates proliferation of supporting cells (SCs) and mitotic regeneration of HCs in neonatal mouse cochlea in vivo and in vitro. Through lineage tracing, we identify that a majority of the proliferating SCs and mitotic-generated HCs induced by Notch inhibition are derived from the Wnt-responsive leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5+) progenitor cells. We demonstrate that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5+ progenitor cells to mitotically generate new HCs. Our study reveals a new function of Notch signaling in limiting proliferation and regeneration potential of postnatal cochlear progenitor cells, and provides a new route to regenerate HCs from progenitor cells by interrupting the interaction between the Notch and Wnt pathways. PMID:25535395

  16. Transportin Regulates Major Mitotic Assembly Events: From Spindle to Nuclear Pore Assembly

    PubMed Central

    Lau, Corine K.; Delmar, Valerie A.; Chan, Rene C.; Phung, Quang; Bernis, Cyril; Fichtman, Boris; Rasala, Beth A.

    2009-01-01

    Mitosis in higher eukaryotes is marked by the sequential assembly of two massive structures: the mitotic spindle and the nucleus. Nuclear assembly itself requires the precise formation of both nuclear membranes and nuclear pore complexes. Previously, importin alpha/beta and RanGTP were shown to act as dueling regulators to ensure that these assembly processes occur only in the vicinity of the mitotic chromosomes. We now find that the distantly related karyopherin, transportin, negatively regulates nuclear envelope fusion and nuclear pore assembly in Xenopus egg extracts. We show that transportin—and importin beta—initiate their regulation as early as the first known step of nuclear pore assembly: recruitment of the critical pore-targeting nucleoporin ELYS/MEL-28 to chromatin. Indeed, each karyopherin can interact directly with ELYS. We further define the nucleoporin subunit targets for transportin and importin beta and find them to be largely the same: ELYS, the Nup107/160 complex, Nup53, and the FG nucleoporins. Equally importantly, we find that transportin negatively regulates mitotic spindle assembly. These negative regulatory events are counteracted by RanGTP. We conclude that the interplay of the two negative regulators, transportin and importin beta, along with the positive regulator RanGTP, allows precise choreography of multiple cell cycle assembly events. PMID:19641022

  17. Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast

    PubMed Central

    Grallert, Agnes; Patel, Avinash; Tallada, Victor A.; Chan, Kuan Yoow; Bagley, Steven; Krapp, Andrea; Simanis, Viesturs; Hagan, Iain M

    2012-01-01

    Activation of mitosis promoting factor (MPF) drives mitotic commitment1. In human cells active MPF appears first on centrosomes2. We show that local activation of MPF on the equivalent organelle of fission yeast, the spindle pole body (SPB), promotes Polo kinase activity at the SPBs long before global MPF activation drives mitotic commitment. Artificially promoting MPF or Polo activity at various locations revealed that this local control of Plo1 activity on G2 phase SPBs dictates the timing of mitotic commitment. Cytokinesis of the rod shaped fission yeast cell generates a naïve “new” cell end. Growth is restricted to the experienced old end until a point in G2 phase called “New End Take Off” (NETO) when bipolar growth is triggered3. NETO coincided with MPF activation of Plo1 on G2 phase SPBs4. Both MPF and Polo activities were required for NETO and both induced NETO when ectopically activated at interphase SPBs. NETO promotion by MPF required polo. Thus, local MPF activation on G2 SPBs directs polo kinase to control at least two distinct and temporally separated, cell cycle transitions at remote locations. PMID:23222840

  18. PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator

    PubMed Central

    Kim, Yoosik; Lee, Jung Hyun; Park, Jong-Eun; Cho, Jun; Yi, Hyerim; Kim, V. Narry

    2014-01-01

    dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well known for its roles in immune response. Upon binding to viral dsRNA, PKR undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates translation and multiple signaling pathways in infected cells. Here, we found that PKR is activated in uninfected cells, specifically during mitosis, by binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu-containing RNAs are segregated in the cytosol and nucleus of interphase cells, respectively, they interact during mitosis when nuclear structure is disrupted. Once phosphorylated, PKR suppresses global translation by phosphorylating the ? subunit of eukaryotic initiation factor 2 (eIF2?). In addition, pPKR acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels of multiple mitotic factors such as CYCLINS A and B and POLO-LIKE KINASE 1 and phosphorylation of HISTONE H3. Disruption of PKR activation via RNAi or expression of a transdominant-negative mutant leads to misregulation of the mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our study unveils a novel function of PKR and endogenous dsRNAs as signaling molecules during the mitosis of uninfected cells. PMID:24939934

  19. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone

    PubMed Central

    Mollinari, Cristiana; Kleman, Jean-Philippe; Jiang, Wei; Schoehn, Guy; Hunter, Tony; Margolis, Robert L.

    2002-01-01

    Midzone microtubules of mammalian cells play an essential role in the induction of cell cleavage, serving as a platform for a number of proteins that play a part in cytokinesis. We demonstrate that PRC1, a mitotic spindle-associated Cdk substrate that is essential to cell cleavage, is a microtubule binding and bundling protein both in vivo and in vitro. Overexpression of PRC1 extensively bundles interphase microtubules, but does not affect early mitotic spindle organization. PRC1 contains two Cdk phosphorylation motifs, and phosphorylation is possibly important to mitotic suppression of bundling, as a Cdk phosphorylation-null mutant causes extensive bundling of the prometaphase spindle. Complete suppression of PRC1 by siRNA causes failure of microtubule interdigitation between half spindles and the absence of a spindle midzone. Truncation mutants demonstrate that the NH2-terminal region of PRC1, rich in ?-helical sequence, is important for localization to the cleavage furrow and to the center of the midbody, whereas the central region, with the highest sequence homology between species, is required for microtubule binding and bundling activity. We conclude that PRC1 is a microtubule-associated protein required to maintain the spindle midzone, and that distinct functions are associated with modular elements of the primary sequence. PMID:12082078

  20. EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis.

    PubMed

    Bañón-Rodríguez, Inmaculada; Gálvez-Santisteban, Manuel; Vergarajauregui, Silvia; Bosch, Minerva; Borreguero-Pascual, Arantxa; Martín-Belmonte, Fernando

    2014-01-13

    Establishing the correct orientation of the mitotic spindle is an essential step in epithelial cell division in order to ensure that epithelial tubules form correctly during organ development and regeneration. While recent findings have identified some of the molecular mechanisms that underlie spindle orientation, many aspects of this process remain poorly understood. Here, we have used the 3D-MDCK model system to demonstrate a key role for a newly identified protein complex formed by IQGAP1 and the epithelial growth factor receptor (EGFR) in controlling the orientation of the mitotic spindle. IQGAP1 is a scaffolding protein that regulates many cellular pathways, from cell-cell adhesion to microtubule organization, and its localization in the basolateral membrane ensures correct spindle orientation. Through its IQ motifs, IQGAP1 binds to EGFR, which is responsible for maintaining IQGAP1 in the basolateral membrane domain. Silencing IQGAP1, or disrupting the basolateral localization of either IQGAP1 or EGFR, results in a non-polarized distribution of NuMA, mitotic spindle misorientation and defects in single lumen formation. PMID:24421325

  1. Population dynamics of a meiotic/mitotic expansion model for the fragile X syndrome

    SciTech Connect

    Ashley, A.E.; Sherman, S.L. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1995-12-01

    A model to explain the mutational process and population dynamics of the fragile X syndrome is presented. The mutational mechanism was assumed to be a multi-pathway, multistep process. Expansion of CGG repeats was based on an underlying biological process and was assumed to occur at two time points: meiosis and early embryonic development (mitosis). Meiotic expansion was assumed to occur equally in oogenesis and spermatogenesis, while mitotic expansion was restricted to somatic, or constitutional, alleles of maternal origin. Testable hypotheses were predicted by this meiotic/mitotic model. First, parental origin of mutation is predicted to be associated with the risk of a woman to have a full-mutation child. Second, {open_quotes}contractions{close_quotes} seen in premutation male transmissions are predicted not to be true contractions in repeat size, but a consequence of the lack of mitotic expansion in paternally derived alleles. Third, a portion of full-mutation males should have full-mutation alleles in their sperm, due to the lack of complete selection against the full-mutation female. Fourth, a specific premutation-allele frequency distribution is predicted and differs from that based on models assuming only meiotic expansion. Last, it is predicted that {approximately}65 generations are required to achieve equilibrium, but this depends greatly on the expansion probabilities. 42 refs., 4 figs., 4 tabs.

  2. Dovitinib induces mitotic defects and activates the G2 DNA damage checkpoint.

    PubMed

    Man, Wing Yu; Mak, Joyce P Y; Poon, Randy Y C

    2014-01-01

    Dovitinib (TKI258; formerly CHIR-258) is an orally bioavailable inhibitor of multiple receptor tyrosine kinases. Interestingly, Dovitinib triggered a G2 /M arrest in cancer cell lines from diverse origins including HeLa, nasopharyngeal carcinoma, and hepatocellular carcinoma. Single-cell analysis revealed that Dovitinib promoted a delay in mitotic exit in a subset of cells, causing the cells to undergo mitotic slippage. Higher concentrations of Dovitinib induced a G2 arrest similar to the G2 DNA damage checkpoint. In support of this, DNA damage was triggered by Dovitinib as revealed by ?-H2AX and comet assays. The mitotic kinase CDK1 was found to be inactivated by phosphorylation in the presence of Dovitinib. Furthermore, the G2 arrest could be overcome by abrogation of the G2 DNA damage checkpoint using small molecule inhibitors of CHK1 and WEE1. Finally, Dovitinib-mediated G2 cell cycle arrest and subsequent cell death could be promoted after DNA damage repair was disrupted by inhibitors of poly(ADP-ribose) polymerases. These results are consistent with the recent finding that Dovitinib can also target topoisomerases. Collectively, these results suggest additional directions for use of Dovitinib, in particular with agents that target the DNA damage checkpoint. PMID:24238094

  3. Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression

    PubMed Central

    Wang, Peng; Galan, Jacob A.; Normandin, Karine; Bonneil, Éric; Hickson, Gilles R.; Roux, Philippe P.; Thibault, Pierre

    2013-01-01

    Cell division requires the coordination of critical protein kinases and phosphatases. Greatwall (Gwl) kinase activity inactivates PP2A-B55 at mitotic entry to promote the phosphorylation of cyclin B–Cdk1 substrates, but how Gwl is regulated is poorly understood. We found that the subcellular localization of Gwl changed dramatically during the cell cycle in Drosophila. Gwl translocated from the nucleus to the cytoplasm in prophase. We identified two critical nuclear localization signals in the central, poorly characterized region of Gwl, which are required for its function. The Polo kinase associated with and phosphorylated Gwl in this region, promoting its binding to 14-3-3? and its localization to the cytoplasm in prophase. Our results suggest that cyclin B–Cdk1 phosphorylation of Gwl is also required for its nuclear exclusion by a distinct mechanism. We show that the nucleo-cytoplasmic regulation of Gwl is essential for its functions in vivo and propose that the spatial regulation of Gwl at mitotic entry contributes to the mitotic switch. PMID:23857770

  4. The ? isoform of topoisomerase II is required for hypercompaction of mitotic chromosomes in human cells

    PubMed Central

    Farr, Christine J.; Antoniou-Kourounioti, Melissa; Mimmack, Michael L.; Volkov, Arsen; Porter, Andrew C. G.

    2014-01-01

    As proliferating cells transit from interphase into M-phase, chromatin undergoes extensive reorganization, and topoisomerase (topo) II?, the major isoform of this enzyme present in cycling vertebrate cells, plays a key role in this process. In this study, a human cell line conditional null mutant for topo II? and a derivative expressing an auxin-inducible degron (AID)-tagged version of the protein have been used to distinguish real mitotic chromosome functions of topo II? from its more general role in DNA metabolism and to investigate whether topo II? makes any contribution to mitotic chromosome formation. We show that topo II? does contribute, with endogenous levels being sufficient for the initial stages of axial shortening. However, a significant effect of topo II? depletion, seen with or without the co-depletion of topo II?, is the failure of chromosomes to hypercompact when delayed in M-phase. This requires much higher levels of topo II protein and is impaired by drugs or mutations that affect enzyme activity. A prolonged delay at the G2/M border results in hyperefficient axial shortening, a process that is topo II?-dependent. Rapid depletion of topo II? has allowed us to show that its function during late G2 and M-phase is truly required for shaping mitotic chromosomes. PMID:24476913

  5. EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis

    PubMed Central

    Bañón-Rodríguez, Inmaculada; Gálvez-Santisteban, Manuel; Vergarajauregui, Silvia; Bosch, Minerva; Borreguero-Pascual, Arantxa; Martín-Belmonte, Fernando

    2014-01-01

    Establishing the correct orientation of the mitotic spindle is an essential step in epithelial cell division in order to ensure that epithelial tubules form correctly during organ development and regeneration. While recent findings have identified some of the molecular mechanisms that underlie spindle orientation, many aspects of this process remain poorly understood. Here, we have used the 3D-MDCK model system to demonstrate a key role for a newly identified protein complex formed by IQGAP1 and the epithelial growth factor receptor (EGFR) in controlling the orientation of the mitotic spindle. IQGAP1 is a scaffolding protein that regulates many cellular pathways, from cell-cell adhesion to microtubule organization, and its localization in the basolateral membrane ensures correct spindle orientation. Through its IQ motifs, IQGAP1 binds to EGFR, which is responsible for maintaining IQGAP1 in the basolateral membrane domain. Silencing IQGAP1, or disrupting the basolateral localization of either IQGAP1 or EGFR, results in a non-polarized distribution of NuMA, mitotic spindle misorientation and defects in single lumen formation. PMID:24421325

  6. Disruption of a conserved CAP-D3 threonine alters condensin loading on mitotic chromosomes leading to chromosome hypercondensation.

    PubMed

    Bakhrebah, Muhammed; Zhang, Tao; Mann, Jeff R; Kalitsis, Paul; Hudson, Damien F

    2015-03-01

    The condensin complex plays a key role in organizing mitotic chromosomes. In vertebrates, there are two condensin complexes that have independent and cooperative roles in folding mitotic chromosomes. In this study, we dissect the role of a putative Cdk1 site on the condensin II subunit CAP-D3 in chicken DT40 cells. This conserved site has been shown to activate condensin II during prophase in human cells, and facilitate further phosphorylation by polo-like kinase I. We examined the functional significance of this phosphorylation mark by mutating the orthologous site of CAP-D3 (CAP-D3(T1403A)) in chicken DT40 cells. We show that this mutation is a gain of function mutant in chicken cells; it disrupts prophase, results in a dramatic shortening of the mitotic chromosome axis, and leads to abnormal INCENP localization. Our results imply phosphorylation of CAP-D3 acts to limit condensin II binding onto mitotic chromosomes. We present the first in vivo example that alters the ratio of condensin I:II on mitotic chromosomes. Our results demonstrate this ratio is a critical determinant in shaping mitotic chromosomes. PMID:25605712

  7. High mountain soils and periglacial features at the Torres del Paine, National Park Torres del Paine, Chile.

    NASA Astrophysics Data System (ADS)

    Senra, Eduardo; Schaefer, Carlos; Simas, Felipe; Gjorup, Davi

    2015-04-01

    The Torres del Paine National Park (TPNP) is located on the southern limit of the Andean Southern Ice Field, part of the Magallanes and Antartica Chilena region, in the province of Ultima Esperanza. The TPNP has a very heterogeneous climate due to orographic influence and wet air masses from the Pacific. The geology is basically Cretaceous metasedimentary rocks and Miocene granitic plutons and batholiths. We studied the main soils and geoenvironments of Mt Ferrier mountain and its surroundings, based on soils , landforms and vegetation aspects. The geoenvironmental stratification was based on the combined variation and integration of pedo-litho-geomorphological features with the vegetation. WE used detailed geological maps, a DEM and slope maps and WorlView II satellite images. Fifteen soils profiles were sampled and classified according to Soil Taxonomy (2010) at all genovironments, ranging from 50 m a.s.l to the at high plateau just below the permanent snowline, under periglacial conditions (~1004m asl). Three soil temperature and moisture monitoring sites were set, allowing for 24 consecutive months (2011 to 2013). Seven geoenvironments were identified with distinct soil and landform characteristics, all with a similar geological substrate. The landform and vegetation have a strong connection with the landscape dynamic, controlling erosional and depositional processes, resulting from glacier advances and retreats in the Late Quaternary. Wind blown materials is widespread, in the form of loess material, accumulating in the higher parts of the landscape. On the other hand, accumulation of organic matter in the water-saturated depressions is common in all altitudes. Generally the soils are acidic and dystrophic, with little exceptions. The following geoenvironments were identified: Periglacial Tundra, Loess slopes, Talus and scarpmentd, Fluvio-glacial terraces, Fluvio-lacustrine plains, Moraines and Paleodunes. The regional pedology show the occurrence of five soil orders (Soil Taxonomy, 2010): Histosols, Mollisols, Inceptsols, Entisols and Andisols.

  8. [Features of chronic pulmonary diseases in workers engaged in the production of high aluminum mullite refractory items].

    PubMed

    Fishman, B B

    2003-01-01

    The article represents features for differential diagnosis between pulmonary tuberculosis and dust diseases in workers engaged into mullite refractories production. The author suggests possible course of the disease as a new type of chronic pulmonary malady--mullitosis. PMID:12958876

  9. The mitotic apparatus. Physical chemical characterization of the 22S protein component and its subunits.

    PubMed

    Stephens, R E

    1967-02-01

    The major 22S protein of the hexylene glycol-isolated mitotic apparatus has been characterized from spindle isolates and extracts of whole eggs and acetone powders of eggs from the sea urchins Strongylocentrotus purpuratus, Strongylocentrotus droebachiensis, and Arbacia punctulata. The protein is free of nucleotide, lipid, and ATPase activity. Essentially identical in amino acid composition, proteins from these species show a relatively high content of glutamic and aspartic acids and are fairly rich in hydrophobic amino acids. Optical rotatory dispersion studies indicate a helical content of about 20%, a value consistent with the proline content of the protein. The purified proteins have sedimentation rates in the range of 22-24S, diffusion constants of 2.4-2.5F, intrinsic viscosities of 3.7-4.3 ml/g, a partial specific volume of 0.74, and an average molecular weight of 880,000. Electron microscopy indicates a globular molecule with dimensions of approximately 150 by 200 A; such size and symmetry are consistent with hydrodynamic measurements. The 22S protein yields 6-7S, 9-10S, and 13-14S subunits below pH 4 or above pH 11. The 13-14S component has an estimated molecular weight of 600,000-700,000. A 5-6S particle is formed in 8 M urea or 5 M guanidine hydrochloride, while at pH 12 the 6-7S subunit is seen; each particle has a molecular weight of 230,000-240,000. In 8 M urea plus 2% mercaptoethanol or at pH 13, the molecular weight becomes 105,000-120,000; under these conditions the particle sediments at 2.5-3S and 4S, respectively. On the basis of these molecular weights, the 6-7S, 9-10S, 13-14S, and the parent 22S particle should be dimer, tetramer, hexamer, and octamer, respectively, of the 105,000-120,000 molecular weight subunit. The various subunits will reform the 22S particle when returned to neutral buffer, with the exception of the mercaptoethanol-treated urea subunit where breakage of disulfide bonds results in a polydisperse aggregate. The 22S particle itself is not susceptible to sulfhydryl reagents, implying either that the disulfide bonds are inaccessible or that they are unnecessary for maintenance of tertiary structure once the 22S particle has formed from subunits. PMID:10976220

  10. Bayesian analysis of X-ray jet features of the high redshift quasar jets observed with Chandra

    NASA Astrophysics Data System (ADS)

    McKeough, Kathryn; Siemiginowska, Aneta; Kashyap, Vinay; Stein, Nathan; Cheung, Chi C.

    2015-01-01

    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. Results from Chandra X-ray and multi-frequency VLA imaging observations of a sample of 11 high- redshift (z > 2) quasars with kilo-parsec scale radio jets are reported. The sample consists of a set of four z ? 3.6 flat-spectrum radio quasars, and seven intermediate redshift (z = 2.1 - 2.9) quasars comprised of four sources with integrated steep radio spectra and three with flat radio spectra.We implement a Bayesian image analysis program, Low-count Image Reconstruction and Analysis (LIRA) , to analyze jet features in the X-ray images of the high redshift quasars. Out of the 36 regions where knots are visible in the radio jets, nine showed detectable X-ray emission. Significant detections are based on the upper bound p-value test based on LIRA simulations. The X-ray and radio properties of this sample combined are examined and compared to lower-redshift samples.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. Work is also supported by the Chandra grant GO4-15099X.

  11. CDK1 substitutes for mTOR kinase to activate mitotic cap-dependent protein translation.

    PubMed

    Shuda, Masahiro; Velásquez, Celestino; Cheng, Erdong; Cordek, Daniel G; Kwun, Hyun Jin; Chang, Yuan; Moore, Patrick S

    2015-05-12

    Mitosis is commonly thought to be associated with reduced cap-dependent protein translation. Here we show an alternative control mechanism for maintaining cap-dependent translation during mitosis revealed by a viral oncoprotein, Merkel cell polyomavirus small T (MCV sT). We find MCV sT to be a promiscuous E3 ligase inhibitor targeting the anaphase-promoting complex, which increases cell mitogenesis. MCV sT binds through its Large T stabilization domain region to cell division cycle protein 20 (Cdc20) and, possibly, cdc20 homolog 1 (Cdh1) E3 ligase adapters. This activates cyclin-dependent kinase 1/cyclin B1 (CDK1/CYCB1) to directly hyperphosphorylate eukaryotic initiation factor 4E (eIF4E)-binding protein (4E-BP1) at authentic sites, generating a mitosis-specific, mechanistic target of rapamycin (mTOR) inhibitor-resistant ? phospho-isoform not present in G1-arrested cells. Recombinant 4E-BP1 inhibits capped mRNA reticulocyte translation, which is partially reversed by CDK1/CYCB1 phosphorylation of 4E-BP1. eIF4G binding to the eIF4E-m(7)GTP cap complex is resistant to mTOR inhibition during mitosis but sensitive during interphase. Flow cytometry, with and without sT, reveals an orthogonal pH3(S10+) mitotic cell population having higher inactive p4E-BP1(T37/T46+) saturation levels than pH3(S10-) interphase cells. Using a Click-iT flow cytometric assay to directly measure mitotic protein synthesis, we find that most new protein synthesis during mitosis is cap-dependent, a result confirmed using the eIF4E/4G inhibitor drug 4E1RCat. For most cell lines tested, cap-dependent translation levels were generally similar between mitotic and interphase cells, and the majority of new mitotic protein synthesis was cap-dependent. These findings suggest that mitotic cap-dependent translation is generally sustained during mitosis by CDK1 phosphorylation of 4E-BP1 even under conditions of reduced mTOR signaling. PMID:25883264

  12. The evaluation of vacuum venting and variotherm process for improving the replication by injection molding of high aspect ratio micro features for biomedical application

    NASA Astrophysics Data System (ADS)

    Sorgato, Marco; Lucchetta, Giovanni

    2015-05-01

    The aspect ratio achievable in replicating micro features is one of the most important process characteristics and it is a major manufacturing constraint in applying injection molding in a range of micro engineering applications. Vacuum venting has been reported to be an effective technique in replicating micro features by microinjection molding. High surface-to-volume ratio and reduced dimensions of micro parts promote the instantaneous drop of melt temperature and consequently lead to incomplete filling. This study aims to investigate the effects of variotherm process, cavity evacuation and their interaction on the production of a micro fluidic filter for biomedical applications. A low-viscosity polystyrene and a cyclic olefin copolymer were molded applying a combination of mold evacuation and a rapid mold temperature variation that keeps the cavity temperature above the glass transition temperature during the injection phase. The research revealed the importance of these molding technologies in enhancing part filling and the replication quality for high aspect ratio micro features.

  13. Cellular and molecular effects of 1GeV/n iron ion exposure on post-mitotic human neurons

    NASA Astrophysics Data System (ADS)

    Guida, Peter; Vazquez, Marcelo E.; Guida, Peter; Kim, Angela

    During space travel, astronauts will be exposed to high energy, high atomic number (HZE) radiation. The potential for damage to cells of the central nervous system following exposure to HZE particle radiation has been characterized as a potential critical risk. Unfortunately, there are very few working model systems of human neurons and as a result, data describing the effects of HZE radiation on them is scarce. To begin risk assessment studies, we utilized an in vitro model consisting of terminally differentiated, post-mitotic human neurons (hNT cells). Previous studies have shown that transplantation of these cells into numerous rodent models of neurological diseases has resulted in successful mitigation of the related disorders, thereby demonstrating their functional relevance. Following exposure of these cells to 1GeV/n Fe ions at the NASA Space Radiation Laboratory, we measured the induction and repair of DNA damage (as revealed by g-H2AX foci), cytotoxicity, gene expression changes, and the induction of apoptosis and its pharmacological reduction. Fluorescence microscopy techniques revealed that there was a dose-dependent induction of g- H2AX foci in hNT cells, with a peak effect 4 hours after exposure (which is significantly longer than for reports using mitotic cells). DNA repair was evident in that the levels of g-H2AX foci were reduced to those in unirradiated cells by 24 hours post-irradiation. Cytotoxicity was also induced in a dose-dependent manner as detected by the fluorescent-based Live/Dead assay. Analysis of the status of the apoptosis-inducing gene p53 showed that the levels of this protein increased significantly 4-8 hours after exposure to Fe ions. By 3 days post-irradiation, annexin V staining demonstrated a dose-dependent induction of apoptosis in the hNT cells. Pre-treatment with two different concentrations of the growth factor TGF-b were effective in reducing the levels of Fe ion-induced apoptosis to statistically significant degrees.

  14. Four important features in the Ward Hunt Ice Shelf revealed from the high-temporal- and high-spatial-resolution images taken by Formosat-2 in Summer 2008

    NASA Astrophysics Data System (ADS)

    Liu, C.; Chang, Y.; Yan, S.; Wu, A.

    2008-12-01

    Massive ice shelf collapsing in Polar Regions is indisputably a clear warning of global warming. To investigate such a rapid change of a breaking up event at a remote site requires an innovative approach that is able to make both high-temporal- and high-spatial-resolution observations. Deploying a high-spatial-resolution sensor in a daily revisit orbit, Formosat-2 successfully captured the details of Wilkins Ice Shelf disintegration event in March 2008, using its 2-m multi-spectral remote sensing imagery. Right after a few extensive fractures were found in the largest ice shelf in the Arctic (Ward Hunt Ice Shelf, WHIS) and reported in May 2008, Formosat-2 was employed to make an intensive observation in this region. A total of eleven scenes of WHIS were acquired from 5 June to 30 August 2008, and ten of them were taken in a preferable low-cloud- cover condition. After the basic processing of level-2 georeferencing, band-to-band coregistration, spectral summation intensity modulation pan-sharpening, and multi-temporal images coregistration, we are able to summarize four important features in WHIS from the time series of Formosat-2 images. First, the sea ice velocity field in the vicinity of WHIS can be inferred by using ice floes as tracers and manually identifying identical floes in consecutive images. There is an eastward flow along the coast of Ellesmere Island. This flow is one of the main forces that gradually tears apart the outermost WHIS in summer. Second, a considerable number of melt ponds with scales of a few to tens of meters is found across the lower part of WHIS. As the temperature rises in summer, the total area of melt ponds increases as a result. In some cases, the melting water soon drains away and a large scale of disintegration occurs afterwards. Third, the extent of organic sedimentary material, namely microbial mat, can be clearly identified from these multispectral images. Fourth, the recent break-up event poses a threat to Disraeli Fiord, the largest remaining epishelf lake in the Northern Hemisphere. A new channel has formed recently, which may accelerate the drainage of the epishelf lake. This research demonstrates that high-spatial- and high- temporal-resolution optical imagery taken from Formosat-2 is a useful data source for studying the collapse of ice shelf in Polar Regions.

  15. Psychometric Features of the General Aptitude Test-Verbal Part (GAT-V): A Large-Scale Assessment of High School Graduates in Saudi Arabia

    ERIC Educational Resources Information Center

    Dimitrov, Dimiter M.; Shamrani, Abdul Rahman

    2015-01-01

    This study examines the psychometric features of a General Aptitude Test-Verbal Part, which is used with assessments of high school graduates in Saudi Arabia. The data supported a bifactor model, with one general factor and three content domains (Analogy, Sentence Completion, and Reading Comprehension) as latent aspects of verbal aptitude.

  16. Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex

    PubMed Central

    Vicente, Juan-Jesus; Cande, W. Zacheus

    2014-01-01

    The binucleate pathogen Giardia intestinalis is a highly divergent eukaryote with a semiopen mitosis, lacking an anaphase-promoting complex/cyclosome (APC/C) and many of the mitotic checkpoint complex (MCC) proteins. However, Giardia has some MCC components (Bub3, Mad2, and Mps1) and proteins from the cohesin system (Smc1 and Smc3). Mad2 localizes to the cytoplasm, but Bub3 and Mps1 are either located on chromosomes or in the cytoplasm, depending on the cell cycle stage. Depletion of Bub3, Mad2, or Mps1 resulted in a lowered mitotic index, errors in chromosome segregation (including lagging chromosomes), and abnormalities in spindle morphology. During interphase, MCC knockdown cells have an abnormal number of nuclei, either one nucleus usually on the left-hand side of the cell or two nuclei with one mislocalized. These results suggest that the minimal set of MCC proteins in Giardia play a major role in regulating many aspects of mitosis, including chromosome segregation, coordination of mitosis between the two nuclei, and subsequent nuclear positioning. The critical importance of MCC proteins in an organism that lacks their canonical target, the APC/C, suggests a broader role for these proteins and hints at new pathways to be discovered. PMID:25057014

  17. Abstract--Subtle force feelings caused by contacts at sharp geometric features are necessary to achieve high-fidelity haptic

    E-print Network

    involving medical training tasks and dexterous engineering manipulation, such as dental surgical simulation to be interacted, such as the ridges on the occlusal surface of teeth and sharp splined shaft and hole as shown objects with sharp features. The ridges on the occlusal surface of tooth (left) and sharp splined shaft

  18. Unsupervised Linear Feature-Extraction Methods and Their Effects in the Classification of High-Dimensional Data

    Microsoft Academic Search

    Luis O. Jimenez-Rodriguez; Emmanuel Arzuaga-Cruz; Miguel Velez-Reyes

    2007-01-01

    This paper presents an analysis and a comparison of different linear unsupervised feature-extraction methods applied to hyperdimensional data and their impact on classification. The dimensionality reduction methods studied are under the category of unsupervised linear transformations: principal component analysis, projection pursuit (PP), and band subset selection. Special attention is paid to an optimized version of the PP introduced in this

  19. Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit

    PubMed Central

    Yellman, Christopher M.; Roeder, G. Shirleen

    2015-01-01

    Cdc14 phosphatase is a key regulator of exit from mitosis, acting primarily through antagonism of cyclin-dependent kinase, and is also thought to be important for meiosis. Cdc14 is released from its sequestration site in the nucleolus in two stages, first by the non-essential Cdc Fourteen Early Anaphase Release (FEAR) pathway and later by the essential Mitotic Exit Network (MEN), which drives efficient export of Cdc14 to the cytoplasm. We find that Cdc14 is confined to the nucleus during early mitotic anaphase release, and during its meiosis I release. Proteins whose degradation is directed by Cdc14 as a requirement for mitotic exit (e.g. the B-type cyclin, Clb2), remain stable during mitotic FEAR, a result consistent with Cdc14 being restricted to the nucleus and not participating directly in mitotic exit. Cdc14 released by the FEAR pathway has been proposed to have a wide variety of activities, all of which are thought to promote passage through anaphase. Proposed functions of FEAR include stabilization of anaphase spindles, resolution of the rDNA to allow its segregation, and priming of the MEN so that mitotic exit can occur promptly and efficiently. We tested the model for FEAR functions using the FEAR-deficient mutation net1-6cdk. Our cytological observations indicate that, contrary to the current model, FEAR is fully dispensable for timely progression through a series of anaphase landmarks and mitotic exit, although it is required for timely rDNA segregation. The net1-6cdk mutation suppresses temperature-sensitive mutations in MEN genes, suggesting that rather than activating mitotic exit, FEAR either inhibits the MEN or has no direct effect upon it. One interpretation of this result is that FEAR delays MEN activation to ensure that rDNA segregation occurs before mitotic exit. Our findings clarify the distinction between FEAR and MEN-dependent Cdc14 activities and will help guide emerging quantitative models of this cell cycle transition. PMID:26090959

  20. Requirements for Activity of the Yeast Mitotic Recombination Hotspot Hot1: RNA Polymerase I and Multiple Cis-Acting Sequences

    PubMed Central

    Huang, G. S.; Keil, R. L.

    1995-01-01

    When inserted at novel locations in the yeast genome, the Saccharomyces cerevisiae recombination hotspot HOT1 stimulates mitotic exchange in adjacent sequences. HOT1 is derived from the rDNA repeat unit, and the sequences required for the recombination-stimulatory activity closely correspond to the rDNA transcription enhancer and initiation site, suggesting there is an association between high levels of RNA polymerase I transcription and increased recombination. To directly test whether RNA polymerase I is essential for HOT1 activity, a subunit of RNA polymerase I was deleted in a strain in which rRNA is transcribed by RNA polymerase II. HOT1 is completely inactive in this strain. Deletion analysis and site-directed mutagenesis were used to further define the sequences within the rDNA enhancer required for HOT1 activity. These studies show that the enhancer contains at least four distinct regions that are required for hotspot activity. In most cases mutations in these regions also decrease transcription from this element, further confirming the association of recombination and transcription. PMID:8582631

  1. Mitotic centromere-associated kinesin is a novel marker for prognosis and lymph node metastasis in colorectal cancer

    PubMed Central

    Ishikawa, K; Kamohara, Y; Tanaka, F; Haraguchi, N; Mimori, K; Inoue, H; Mori, M

    2008-01-01

    Mitotic centromere-associated kinesin (MCAK) is a microtubule depolymerase that is essential for proper kinetochore–microtubule attachment during spindle formation. Overexpression of MCAK has been correlated with aggressive forms of carcinoma, resulting in poor prognosis of colorectal cancer. The purpose of this study was to quantify MCAK expression in malignant and benign colorectal tissues and to determine if MCAK expression levels correlate with clinicopathologic factors and prognosis in colorectal cancer patients. Paired colorectal tissue samples from tumours and the corresponding normal tissues were obtained from 120 patients with colorectal cancer who underwent surgical resection. The real-time reverse transcriptase-PCR and immunohistochemistry were used to analyse mRNA and protein expression status with respect to various clinicopathological factors. MCAK expression was higher in colorectal cancer tissue (P<0.01) than in corresponding normal tissue, and this elevated expression level was markedly associated with factors such as lymph node metastasis (P=0.0023), venous invasion (P=0.019), peritoneal dissemination (P=0.021) and Dukes' classification (P=0.0023). Patients with high MCAK mRNA expression also showed a far poorer survival rate than those with low MCAK mRNA expression (P<0.01). Elevated MCAK expression was an independent predictor of overall survival and lymph node metastasis. These data suggest that MCAK expression may serve as a good marker of prognosis and lymph node metastasis in colorectal cancer. PMID:18506187

  2. Nitropolycyclic aromatic hydrocarbons are inducers of mitotic homologous recombination in the wing-spot test of Drosophila melanogaster.

    PubMed

    Dihl, R R; Bereta, M S; do Amaral, V S; Lehmann, M; Reguly, M L; de Andrade, H H R

    2008-07-01

    In this study, the widespread environmental pollutants 1-nitronaphthalene (1NN), 1,5-dinitronaphthalene (1,5DNN), 2-nitrofluorene (2NF) and 9-nitroanthracene (9NA), were investigated for genotoxicity in the wing somatic mutation and recombination test (SMART) of Drosophila--using the high bioactivation (HB) cross. Our in vivo experiments demonstrated that all compounds assessed induced genetic toxicity, causing increased incidence of homologous somatic recombination. 2NF, 9NA and 1NN mutant clone induction is almost exclusively related to somatic recombination, although 1,5DNN-clone induction depends on both mutagenic and recombinagenic events. 1NN has the highest recombinagenic activity (approximately 100%), followed by 2NF (approximately 77%), 9NA (approximately 75%) and 1,5DNN (33%). 1NN is the compound with the strongest genotoxicity, with 9NA being approximately 40 times less potent than the former and 2NF and 1,5DNN approximately 333 times less potent than 1NN. The evidence indicating that the major effect observed in this study is an increased frequency of mitotic recombination emphasizes another hazard that could be associated to NPAHs--the increment in homologous recombination (HR). PMID:18440115

  3. Mitotic stability and nuclear inheritance of integrated viral cDNA in engineered hypovirulent strains of the chestnut blight fungus.

    PubMed Central

    Chen, B; Choi, G H; Nuss, D L

    1993-01-01

    Transmissible hypovirulence is a novel form of biological control in which virulence of a fungal pathogen is attenuated by an endogenous RNA virus. The feasibility of engineering hypovirulence was recently demonstrated by transformation of the chestnut blight fungus, Cryphonectria parasitica, with a full-length cDNA copy of a hypovirulence-associated viral RNA. Engineered hypovirulent transformants were found to contain both a chromsomally integrated cDNA copy of the viral genome and a resurrected cytoplasmically replicating double-stranded RNA form. We now report stable maintenance of integrated viral cDNA through repeated rounds of asexual sporulation and passages on host plant tissue. We also demonstrate stable nuclear inheritance of the integrated viral cDNA and resurrection of the cytoplasmic viral double-stranded RNA form in progeny resulting from the mating of an engineered hypovirulent C. parasitica strain and a vegetatively incompatible virulent strain. Mitotic stability of the viral cDNA ensures highly efficient transmission of the hypovirulence phenotype through conidia. Meiotic transmission, a mode not observed for natural hypovirulent strains, introduces virus into ascospore progeny representing a spectrum of vegetative compatibility groups, thereby circumventing barriers to anastomosis-mediated transmission imposed by the fungal vegetative incompatibility system. These transmission properties significantly enhance the potential of engineered hypovirulent C. parasitica strains as effective biocontrol agents. Images PMID:8344241

  4. Use of DEAD-box polypeptide-4 (Ddx4) gene promoter-driven fluorescent reporter mice to identify mitotically active germ cells in post-natal mouse ovaries.

    PubMed

    Park, Eun-Sil; Tilly, Jonathan L

    2015-01-01

    Several laboratories have independently isolated mitotically active germ cells, termed female germline stem cells or oogonial stem cells (OSCs), from adult mouse ovaries. However, a recent study using Ddx4-Cre;Rosa26 reporter mice concluded that such germ cells do not exist. Given the disparity in conclusions drawn in this study compared with others, we felt it was important to re-assess the utility of Ddx4-Cre;Rosa26 reporter mice for identification of OSCs in adult mouse ovaries. Transgenic Ddx4-Cre mice were crossed with Rosa26(tdTm/tdTm) mice to drive restricted tomato red (tdTm) gene expression in cells in which the Ddx4 gene promoter has been activated. Crude dispersion of ovaries from recombined offspring generated cell fractions containing tdTm-positive immature oocytes, which are incapable of proliferation and thus probably represent the uncharacterized reporter-positive ovarian cells identified in the paper Zhang et al. (2012) as being mitotically inactive. Dispersed ovaries further subjected to fluorescence-activated cell sorting yielded a large population of non-germline tdTm-positive cells, indicative of promoter 'leakiness' in the Ddx4-Cre mouse line. Nonetheless, a small percentage of these tdTm-positive cells exhibited externalized (extracellular, ec) expression of Ddx4 protein (ecDdx4-positive), expressed markers of primitive germ cells but not of oocytes, and actively proliferated in culture, all of which are characteristic features of OSCs. Thus, crude dispersion of ovaries collected from Ddx4 gene promoter-driven reporter mice is not, by itself, a reliable approach to identify OSCs, whereas the same ovarian dispersates further subjected to cell sorting strategies yield purified OSCs that can be expanded in culture. PMID:25147160

  5. Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos.

    PubMed

    Tavernier, Nicolas; Noatynska, Anna; Panbianco, Costanza; Martino, Lisa; Van Hove, Lucie; Schwager, Françoise; Léger, Thibaut; Gotta, Monica; Pintard, Lionel

    2015-03-16

    The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho-SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing. PMID:25753036

  6. The ARF tumor suppressor prevents chromosomal instability and ensures mitotic checkpoint fidelity through regulation of Aurora B

    PubMed Central

    Britigan, Eric M.C.; Wan, Jun; Zasadil, Lauren M.; Ryan, Sean D.; Weaver, Beth A.

    2014-01-01

    The ARF tumor suppressor is part of the CDKN2A locus and is mutated or undetectable in numerous cancers. The best-characterized role for ARF is in stabilizing p53 in response to cellular stress. However, ARF has tumor suppressive functions outside this pathway that have not been fully defined. Primary mouse embryonic fibroblasts (MEFs) lacking the ARF tumor suppressor contain abnormal numbers of chromosomes. However, no role for ARF in cell division has previously been proposed. Here we demonstrate a novel, p53-independent role for ARF in the mitotic checkpoint. Consistent with this, loss of ARF results in aneuploidy in vitro and in vivo. ARF?/? MEFs exhibit mitotic defects including misaligned and lagging chromosomes, multipolar spindles, and increased tetraploidy. ARF?/? cells exhibit overexpression of Mad2, BubR1, and Aurora B, but only overexpression of Aurora B phenocopies mitotic defects observed in ARF?/? MEFs. Restoring Aurora B to near-normal levels rescues mitotic phenotypes in cells lacking ARF. Our results define an unexpected role for ARF in chromosome segregation and mitotic checkpoint function. They further establish maintenance of chromosomal stability as one of the additional tumor-suppressive functions of ARF and offer a molecular explanation for the common up-regulation of Aurora B in human cancers. PMID:25057018

  7. Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in mice.

    PubMed Central

    De Sepulveda, P; Guenet, J L; Panthier, J J

    1995-01-01

    The mouse W locus encodes Kit, the receptor tyrosine kinase for stem cell factor (SCF). Kit is required for several developmental processes, including the proliferation and survival of melanoblasts. Because of the nearly complete failure of Wrio/+ melanoblasts to colonize the skin, the costs of Wrio/+ mice are characterized by a majority of white hairs interspersed among pigmented hairs, giving a roan effect. However, 3.6% of Wrio/+ mice exhibit phenotypic reversions, i.e., spots of wild-type color on their coats with an otherwise mutant phenotype. Melanocyte cell lines were derived from each of six independent reversion spots on the skin of (C57BL/6 x DBA/2)F1 Wrio/+ mice. All six melanocyte cell lines exhibited the general characteristics common to normal, nonimmortal mouse melanocytes. Of these, three revertant cell lines had lost the dominant-negative Wrio allele following mitotic recombination between the centromere and the W locus. One of the cell lines remained Wrio/+ but showed (i) stimulation in response to SCF and (ii) increased Kit expression, suggesting that the Wrio mutation can be rescued by increased endogenous expression of the c-kit proto-oncogene. Finally, two cell lines showed no detectable genetic change at the W/Kit locus and failed to respond to SCF stimulation in vitro. These results demonstrate that mitotic recombination can create large patches of wild-type hair on the coats of Wrio/+ mutant mice. This shows that mitotic recombination occurs spontaneously in normal healthy tissue in vivo. Moreover, these experiments confirm that other mechanisms, not associated with loss of heterozygosity, may account for the coat color reversion phenotype. PMID:7565742

  8. Studying the Space Weather Features of the High-Latitude Ionosphere by Using a Physics-Based Data Assimilation Model and Observational Data from Ground Magnetometer Arrays

    NASA Astrophysics Data System (ADS)

    Zhu, L.; Schunk, R. W.; Scherliess, L.; Sojka, J. J.; Eccles, J. V.

    2011-12-01

    The high-latitude ionosphere is a very dynamic region in the solar-terrestrial environment. Frequent disturbances in the region can adversely affect numerous military and civilian technologies. Accurate specifications and forecasts of the high-latitude electrodynamic and plasma structures have fundamental space weather importance for enabling mitigation of adverse effects. Presently, most of the space-weather models use limited observations and/or indices to define a set of empirical drivers for physical models to move forward in time. Since the empirical drivers have a "climatological" nature and there are significant physical inconsistencies among various empirical drivers due to independent statistical analysis of different observational data, the specifications of high-latitude space environment from these space weather models cannot truthfully reflect the weather features. In fact, unrealistic small- and large-scale structures could be produced in the specifications and forecasts from these models. We developed a data assimilation model for the high-latitude ionospheric plasma dynamics and electrodynamics to overcome these hurdles. With a set of physical models and an ensemble Kalman filter, the data assimilation model can determine the self-consistent structures of the high-latitude convection electric field, ionospheric conductivity, and the key drivers associated with these quantities by ingesting data from multiple observations. These ingested data include the magnetic perturbation from the ground-based magnetometers in the high-latitude regions, magnetic measurements of IRIDIUM satellites, SuperDARN line-of-sight velocity, and in-situ drift velocity measured by DMSP satellites. As a result, the assimilation model can capture the small- and large-scale plasma structures and sharp electrodynamic boundaries, thus, can provide a more accurate picture of the high-latitude space weather. In this presentation, we will first briefly describe the data-assimilation model of high-latitude electrodynamics and its strengths over the other space-weather models. Then we will present the space weather features produced by the model for quiet and storm periods constrained by the data from ground magnetometer arrays. This will demonstrate the dynamic variability of the high-latitude ionosphere. Finally, we will present high-resolution ionospheric modeling results of the time-evolution and spatial features of the high-latitude plasma structures to further demonstrate the model's capability in producing the space weather features in the high-latitude ionosphere. These results will illuminate the importance of real-time data availability and data assimilation models for accurate specification and forecasting of space weather.

  9. Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo

    E-print Network

    Azuma, Mizuki; Embree, Lisa J.; Sabaawy, Hatem; Hickstein, Dennis D.

    2007-10-03

    Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo Mizuki Azuma*, Lisa J. Embree, Hatem Sabaawy, Dennis D. Hickstein Experimental Transplantation and Immunology Branch, Center for Cancer... Survival in the Zebrafish Embryo. PLoS ONE 2(10): e979. doi:10.1371/journal.pone.0000979 INTRODUCTION The EWSR1 gene is involved in a number of different sarcomas as a result of chromosomal translocations. EWSR1 is fused to an ETS transcription factor (FLI...

  10. Bookmarking promoters in mitotic chromatin: poly(ADP-ribose)polymerase-1 as an epigenetic mark

    PubMed Central

    Lodhi, Niraj; Kossenkov, Andrew V.; Tulin, Alexei V.

    2014-01-01

    Epigenetics are the heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. After mitosis, it is thought that bookmarking transcription factors remain at promoters, regulating which genes become active and which remain silent. Herein, we demonstrate that poly(ADP-ribose)polymerase-1 (PARP-1) is a genome-wide epigenetic memory mark in mitotic chromatin, and we further show that the presence of PARP-1 is absolutely crucial for reactivation of transcription after mitosis. Based on these findings, a novel molecular model of epigenetic memory transmission through the cell cycle is proposed. PMID:24861619

  11. Vanadocenes as potent anti-proliferative agents disrupting mitotic spindle formation in cancer cells.

    PubMed

    Navara, C S; Benyumov, A; Vassilev, A; Narla, R K; Ghosh, P; Uckun, F M

    2001-04-01

    We present experimental data which establish the organometallic compounds vanadocene dichloride (VDC) and vanadocene acetylacetonate (VDacac) as potent anti-proliferative agents. We first examined the effects of VDC and VDacac on the rapid embryonic cell division and development of Zebrafish. Both compounds were capable of causing cell division block at the 8-16 cell stage of embryonic development followed by total cell fusion and developmental arrest. We next examined the effect of VDC and VDacac on proliferation of human breast cancer and glioblastoma cell lines using MTT assays. VDC inhibited the proliferation of the breast cancer cell line BT-20 as well as the glioblastoma cell line U373 in a concentration-dependent fashion with IC50 values of 11.0, 14.9 and 18.6 microM, respectively. VDacac inhibited cellular proliferation with IC50 values of 9.1, 26.9 and 35.5 microM, respectively. Whereas in vehicle-treated control cancer cells mitotic spindles were organized as a bipolar microtubule array and the DNA was organized on a metaphase plate, vanadocene-treated cancer cells had aberrant monopolar mitotic structures where microtubules were detected only on one side of the chromosomes and the chromosomes were arranged in a circular pattern. In contrast to control cells which showed a single focus of gamma-tubulin at each pole of the bipolar mitotic spindle, VDC- or VDacac-treated cells had two foci of gamma-tubulin on the same side of the chromosomes resulting in a broad centrosome at one pole. All monopolar spindles examined had two foci of gamma-tubulin labeling consistent with a mechanism in which the centrosomes duplicate but do not separate properly to form a bipolar spindle. These results provide unprecedented evidence that organometallic compounds can block cell division in human cancer cells by disrupting bipolar spindle formation. In accordance with these results vanadocene treatment caused an arrest at the G2/M phase of the cell cycle. This unique mechanism of anti-mitotic function warrants further development of vanadocene complexes as anti-cancer drugs. PMID:11335794

  12. Sorting by COP I-coated vesicles under interphase and mitotic conditions

    PubMed Central

    1996-01-01

    COP I-coated vesicles were analyzed for their content of resident Golgi enzymes (N-acetylgalactosaminyltransferase; N- acetylglucosaminyltransferase I; mannosidase II; galactosyltransferase), cargo (rat serum albumin; polyimmunoglobulin receptor), and recycling proteins (-KDEL receptor; ERGIC-53/p58) using biochemical and morphological techniques. The levels of these proteins were similar when the vesicles were prepared under interphase or mitotic conditions showing that sorting was unaffected. The average density relative to starting membranes for resident enzymes (14-30%), cargo (16-23%), and recycling proteins (81-125%) provides clues to the function of COP I vesicles in transport through the Golgi apparatus. PMID:8830771

  13. A 90nm high volume manufacturing logic technology featuring novel 45nm gate length strained silicon CMOS transistors

    Microsoft Academic Search

    T. Ghani; M. Armstrong; C. Auth; M. Bost; P. Charvat; G. Glass; T. Hoffmann; K. Johnson; C. Kenyon; J. Klaus; B. McIntyre; K. Mistry; A. Murthy; J. Sandford; M. Silberstein; S. Sivakumar; P. Smith; K. Zawadzki; S. Thompson; M. Bohr

    2003-01-01

    This paper describes the details of a novel strained transistor architecture which is incorporated into a 90nm logic technology on 300mm wafers. The unique strained PMOS transistor structure features an epitaxially grown strained SiGe film embedded in the source drain regions. Dramatic performance enhancement relative to unstrained devices are reported. These transistors have gate length of 45nm and 50nm for

  14. A Low Complexity Parabolic Lip Contour Model With Speaker Normalization For High-Level Feature Extraction in Noise Robust Audio-Visual Speech Recognition

    Microsoft Academic Search

    Bengt J. Borgstrom; Abeer Alwan

    This paper proposes a novel low complexity lip contour model for high-level optic feature extraction in noise robust AV-ASR systems. The model is based on weighted least-squares parabolic fitting of the upper and lower lip contours and does not require the assumption of symmetry across the horizontal axis of the mouth, and therefore is realistic. The proposed model does not

  15. A Low-Complexity Parabolic Lip Contour Model With Speaker Normalization for High-Level Feature Extraction in Noise-Robust Audiovisual Speech Recognition

    Microsoft Academic Search

    Bengt Jonas Borgstrom; Abeer Alwan

    2008-01-01

    This paper proposes a novel low-complexity lip contour model for high-level optic feature extraction in noise-robust audiovisual (AV) automatic speech recognition systems. The model is based on weighted least-squares parabolic fitting of the upper and lower lip contours, does not require the assumption of symmetry across the horizontal axis of the mouth, and is therefore realistic. The proposed model does

  16. A 667 MHz Logic-Compatible Embedded DRAM Featuring an Asymmetric 2T Gain Cell for High Speed On-Die Caches

    Microsoft Academic Search

    Ki Chul Chun; Pulkit Jain; Tae-Ho Kim; Chris H. Kim

    2012-01-01

    Circuit techniques for enhancing the retention time and random cycle of logic-compatible embedded DRAMs (eDRAMs) are presented. An asymmetric 2T gain cell utilizes the gate and junction leakages of a PMOS write device to maintain a high data ‘1’ voltage level which enables fast read access using an NMOS read device. A current-mode sense amplifier (C-S\\/A) featuring a cross-coupled PMOS

  17. Phosphorylation of Crm1 by CDK1-cyclin-B promotes Ran-dependent mitotic spindle assembly.

    PubMed

    Wu, Zhige; Jiang, Qing; Clarke, Paul R; Zhang, Chuanmao

    2013-08-01

    Mitotic spindle assembly in animal cells is orchestrated by a chromosome-dependent pathway that directs microtubule stabilization. RanGTP generated at chromosomes releases spindle assembly factors from inhibitory complexes with importins, the nuclear transport factors that facilitate protein import into the nucleus during interphase. In addition, the nuclear export factor Crm1 has been proposed to act as a mitotic effector of RanGTP through the localized assembly of protein complexes on the mitotic spindle, notably at centrosomes and kinetochores. It has been unclear, however, how the functions of nuclear transport factors are controlled during mitosis. Here, we report that human Crm1 is phosphorylated at serine 391 in mitosis by CDK1-cyclin-B (i.e. the CDK1 and cyclin B complex). Expression of Crm1 with serine 391 mutated to either non-phosphorylated or phosphorylation-mimicking residues indicates that phosphorylation directs the localization of Crm1 to the mitotic spindle and facilitates spindle assembly, microtubule stabilization and chromosome alignment. We find that phosphorylation of Crm1 at serine 391 enhances its RanGTP-dependent interaction with RanGAP1-RanBP2 and promotes their recruitment to the mitotic spindle. These results show that phosphorylation of Crm1 controls its molecular interactions, localization and function during mitosis, uncovering a new mechanism for the control of mitotic spindle assembly by CDK1-cyclin-B. We propose that nuclear transport factors are controlled during mitosis through the selection of specific molecular interactions by protein phosphorylation. PMID:23729730

  18. Oocyte formation by mitotically-active germ cells purified from ovaries of reproductive age women

    PubMed Central

    White, Yvonne A. R.; Woods, Dori C.; Takai, Yasushi; Ishihara, Osamu; Seki, Hiroyuki; Tilly, Jonathan L.

    2012-01-01

    Germline stem cells that produce oocytes in vitro and fertilization-competent eggs in vivo have been identified in and isolated from adult mouse ovaries. Here we describe and validate a FACS-based protocol that can be used with adult mouse ovaries and human ovarian cortical tissue to purify rare mitotically-active cells that exhibit a gene expression profile consistent with primitive germ cells. Once established in vitro, these cells can be expanded for months and spontaneously generate 35–50 µm oocytes, as determined by morphology, gene expression and attainment of haploid (1n) status. Injection of the human germline cells, engineered to stably express GFP, into human ovarian cortical biopsies leads to formation of follicles containing GFP-positive oocytes 1–2 weeks after xenotransplantation into immunodeficient female mice. Thus, ovaries of reproductive-age women, like adult mice, possess rare mitotically-active germ cells that can be propagated in vitro as well as generate oocytes in vitro and in vivo. PMID:22366948

  19. Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.

    PubMed

    Exertier, Prisca; Javerzat, Sophie; Wang, Baigang; Franco, Mélanie; Herbert, John; Platonova, Natalia; Winandy, Marie; Pujol, Nadège; Nivelles, Olivier; Ormenese, Sandra; Godard, Virginie; Becker, Jürgen; Bicknell, Roy; Pineau, Raphael; Wilting, Jörg; Bikfalvi, Andreas; Hagedorn, Martin

    2013-12-01

    Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors. PMID:24327603

  20. Mitotic fidelity requires transgenerational action of a testis-restricted HP1

    PubMed Central

    Levine, Mia T; Vander Wende, Helen M; Malik, Harmit S

    2015-01-01

    Sperm-packaged DNA must undergo extensive reorganization to ensure its timely participation in embryonic mitosis. Whereas maternal control over this remodeling is well described, paternal contributions are virtually unknown. In this study, we show that Drosophila melanogaster males lacking Heterochromatin Protein 1E (HP1E) sire inviable embryos that undergo catastrophic mitosis. In these embryos, the paternal genome fails to condense and resolve into sister chromatids in synchrony with the maternal genome. This delay leads to a failure of paternal chromosomes, particularly the heterochromatin-rich sex chromosomes, to separate on the first mitotic spindle. Remarkably, HP1E is not inherited on mature sperm chromatin. Instead, HP1E primes paternal chromosomes during spermatogenesis to ensure faithful segregation post-fertilization. This transgenerational effect suggests that maternal control is necessary but not sufficient for transforming sperm DNA into a mitotically competent pronucleus. Instead, paternal action during spermiogenesis exerts post-fertilization control to ensure faithful chromosome segregation in the embryo. DOI: http://dx.doi.org/10.7554/eLife.07378.001

  1. Amitozyn Impairs Chromosome Segregation and Induces Apoptosis via Mitotic Checkpoint Activation

    PubMed Central

    Potopalsky, Anatoly I.; Chroboczek, Jadwiga; Tcherniuk, Sergey O.

    2013-01-01

    Amitozyn (Am) is a semi-synthetic drug produced by the alkylation of major celandine (Chelidonium majus L.) alkaloids with the organophosphorous compound N,N’N’-triethylenethiophosphoramide (ThioTEPA). We show here that the treatment of living cells with Am reversibly perturbs the microtubule cytoskeleton, provoking a dose-dependent cell arrest in the M phase. Am changed the dynamics of tubulin polymerization in vitro, promoted the appearance of aberrant mitotic phenotypes in HeLa cells and induced apoptosis by the activation of caspase-9, caspase-3 and PARP, without inducing DNA breaks. Am treatment of HeLa cells induced changes in the phosphorylation of the growth suppressor pRb that coincided with maximum mitotic index. The dose-dependent and reversible anti-proliferative effect of Am was observed in several transformed cell lines. Importantly, the drug was also efficient against multidrug-resistant, paclitaxel-resistant or p53-deficient cells. Our results thus open the way to further pre-clinical evaluation of Am. PMID:23505430

  2. How Kinesin Motor Proteins Drive Mitotic Spindle Function: Lessons from Molecular Assays

    PubMed Central

    2010-01-01

    Kinesins are enzymes that use the energy of ATP to perform mechanical work. There are approximately 14 families of kinesins within the kinesin superfamily. Family classification is derived primarily from alignments of the sequences of the core motor domain. For this reason, the enzymatic behavior and motility of each motor generally reflects its family. At the cellular level, kinesin motors perform a variety of functions during cell division and within the mitotic spindle to ensure that chromosomes are segregated with the highest fidelity possible. The cellular functions of these motors are intimately related to their mechanical and enzymatic properties at the single molecule level. For this reason, motility studies designed to evaluate the activity of purified molecular motors are a requirement in order to understand, mechanistically, how these motors make the mitotic spindle work and what can cause the spindle to fail. This review will focus on a selection of illustrative kinesins, which have been studied at the molecular level in order to inform our understanding of their function in cells. In addition, the review will endeavor to point out some kinesins that have been studied extensively but which still lack sufficient molecular underpinnings to fully predict their contribution to spindle function. PMID:20109570

  3. A novel role of farnesylation in targeting a mitotic checkpoint protein, human Spindly, to kinetochores.

    PubMed

    Moudgil, Devinderjit K; Westcott, Nathan; Famulski, Jakub K; Patel, Kinjal; Macdonald, Dawn; Hang, Howard; Chan, Gordon K T

    2015-03-30

    Kinetochore (KT) localization of mitotic checkpoint proteins is essential for their function during mitosis. hSpindly KT localization is dependent on the RZZ complex and hSpindly recruits the dynein-dynactin complex to KTs during mitosis, but the mechanism of hSpindly KT recruitment is unknown. Through domain-mapping studies we characterized the KT localization domain of hSpindly and discovered it undergoes farnesylation at the C-terminal cysteine residue. The N-terminal 293 residues of hSpindly are dispensable for its KT localization. Inhibition of farnesylation using a farnesyl transferase inhibitor (FTI) abrogated hSpindly KT localization without affecting RZZ complex, CENP-E, and CENP-F KT localization. We showed that hSpindly is farnesylated in vivo and farnesylation is essential for its interaction with the RZZ complex and hence KT localization. FTI treatment and hSpindly knockdown displayed the same mitotic phenotypes, indicating that hSpindly is a key FTI target in mitosis. Our data show a novel role of lipidation in targeting a checkpoint protein to KTs through protein-protein interaction. PMID:25825516

  4. Smc5-Smc6-Dependent Removal of Cohesin from Mitotic Chromosomes ?

    PubMed Central

    Outwin, Emily A.; Irmisch, Anja; Murray, Johanne M.; O'Connell, Matthew J.

    2009-01-01

    The function of the essential cohesin-related Smc5-Smc6 complex has remained elusive, though hypomorphic mutants have defects late in recombination, in checkpoint maintenance, and in chromosome segregation. Recombination and checkpoints are not essential for viability, and Smc5-Smc6-null mutants die in lethal mitoses. This suggests that the chromosome segregation defects may be the source of lethality in irradiated Smc5-Smc6 hypomorphs. We show that in smc6 mutants, following DNA damage in interphase, chromosome arm segregation fails due to an aberrant persistence of cohesin, which is normally removed by the Separase-independent pathway. This postanaphase persistence of cohesin is not dependent on DNA damage, since the synthetic lethality of smc6 hypomorphs with a topoisomerase II mutant, defective in mitotic chromosome structure, is also due to the retention of cohesin on undamaged chromosome arms. In both cases, Separase overexpression bypasses the defect and restores cell viability, showing that defective cohesin removal is a major determinant of the mitotic lethality of Smc5-Smc6 mutants. PMID:19528228

  5. The Emerging Nexus of Active DNA Demethylation and Mitochondrial Oxidative Metabolism in Post-Mitotic Neurons

    PubMed Central

    Meng, Huan; Chen, Guiquan; Gao, Hui-Ming; Song, Xiaoyu; Shi, Yun; Cao, Liu

    2014-01-01

    The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET) methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS) and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons. PMID:25490140

  6. ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy

    PubMed Central

    Maskey, Dipak; Yousefi, Shida; Schmid, Inès; Zlobec, Inti; Perren, Aurel; Friis, Robert; Simon, Hans-Uwe

    2013-01-01

    Anticancer drug therapy activates both molecular cell death and autophagy pathways. Here we show that even sublethal concentrations of DNA-damaging drugs, such as etoposide and cisplatin, induce the expression of autophagy-related protein 5 (ATG5), which is both necessary and sufficient for the subsequent induction of mitotic catastrophe. We demonstrate that ATG5 translocates to the nucleus, where it physically interacts with survivin in response to DNA-damaging agents both in vitro and in carcinoma tissues obtained from patients who had undergone radiotherapy and/or chemotherapy. As a consequence, elements of the chromosomal passenger complex are displaced during mitosis, resulting in chromosome misalignment and segregation defects. Pharmacological inhibition of autophagy does not prevent ATG5-dependent mitotic catastrophe, but shifts the balance to an early caspase-dependent cell death. Our data suggest a dual role for ATG5 in response to drug-induced DNA damage, where it acts in two signalling pathways in two distinct cellular compartments, the cytosol and the nucleus. PMID:23945651

  7. Mitotic fidelity requires transgenerational action of a testis-restricted HP1.

    PubMed

    Levine, Mia T; Vander Wende, Helen M; Malik, Harmit S

    2015-01-01

    Sperm-packaged DNA must undergo extensive reorganization to ensure its timely participation in embryonic mitosis. Whereas maternal control over this remodeling is well described, paternal contributions are virtually unknown. In this study, we show that Drosophila melanogaster males lacking Heterochromatin Protein 1E (HP1E) sire inviable embryos that undergo catastrophic mitosis. In these embryos, the paternal genome fails to condense and resolve into sister chromatids in synchrony with the maternal genome. This delay leads to a failure of paternal chromosomes, particularly the heterochromatin-rich sex chromosomes, to separate on the first mitotic spindle. Remarkably, HP1E is not inherited on mature sperm chromatin. Instead, HP1E primes paternal chromosomes during spermatogenesis to ensure faithful segregation post-fertilization. This transgenerational effect suggests that maternal control is necessary but not sufficient for transforming sperm DNA into a mitotically competent pronucleus. Instead, paternal action during spermiogenesis exerts post-fertilization control to ensure faithful chromosome segregation in the embryo. PMID:26151671

  8. Loss of gene function through rapid mitotic cycles in the Drosophila embryo.

    PubMed

    Rothe, M; Pehl, M; Taubert, H; Jäckle, H

    1992-09-10

    The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development. PMID:1522901

  9. The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1

    PubMed Central

    Steinhäuser, Kerstin; Roth, Susanne; Louwen, Frank; Yuan, Juping

    2015-01-01

    The mitotic centromere-associated kinesin (MCAK), a potent microtubule depolymerase, is involved in regulating microtubule dynamics. The activity and subcellular localization of MCAK are tightly regulated by key mitotic kinases, such as Polo-like kinase 1 (Plk1) by phosphorylating multiple residues in MCAK. Since Plk1 phosphorylates very often different residues of substrates at different stages, we have dissected individual phosphorylation of MCAK by Plk1 and characterized its function in more depth. We have recently shown that S621 in MCAK is the major phosphorylation site of Plk1, which is responsible for regulating MCAK's degradation by promoting the association of MCAK with APC/CCdc20. In the present study, we have addressed another two residues phosphorylated by Plk1, namely S632/S633 in the C-terminus of MCAK. Our data suggest that Plk1 phosphorylates S632/S633 and regulates its catalytic activity in mitosis. This phosphorylation is required for proper spindle assembly during early phases of mitosis. The subsequent dephosphorylation of S632/S633 might be necessary to timely align the chromosomes onto the metaphase plate. Therefore, our studies suggest new mechanisms by which Plk1 regulates MCAK: the degradation of MCAK is controlled by Plk1 phosphorylation on S621, whereas its activity is modulated by Plk1 phosphorylation on S632/S633 in mitosis. PMID:25504441

  10. A novel tropomyosin isoform functions at the mitotic spindle and Golgi in Drosophila.

    PubMed

    Goins, Lauren M; Mullins, R Dyche

    2015-07-01

    Most eukaryotic cells express multiple isoforms of the actin-binding protein tropomyosin that help construct a variety of cytoskeletal networks. Only one nonmuscle tropomyosin (Tm1A) has previously been described in Drosophila, but developmental defects caused by insertion of P-elements near tropomyosin genes imply the existence of additional, nonmuscle isoforms. Using biochemical and molecular genetic approaches, we identified three tropomyosins expressed in Drosophila S2 cells: Tm1A, Tm1J, and Tm2A. The Tm1A isoform localizes to the cell cortex, lamellar actin networks, and the cleavage furrow of dividing cells-always together with myosin-II. Isoforms Tm1J and Tm2A colocalize around the Golgi apparatus with the formin-family protein Diaphanous, and loss of either isoform perturbs cell cycle progression. During mitosis, Tm1J localizes to the mitotic spindle, where it promotes chromosome segregation. Using chimeras, we identified the determinants of tropomyosin localization near the C-terminus. This work 1) identifies and characterizes previously unknown nonmuscle tropomyosins in Drosophila, 2) reveals a function for tropomyosin in the mitotic spindle, and 3) uncovers sequence elements that specify isoform-specific localizations and functions of tropomyosin. PMID:25971803

  11. Post-mitotic role of nucleostemin as a promoter of skeletal muscle cell differentiation

    SciTech Connect

    Hirai, Hiroyuki; Romanova, Liudmila; Kellner, Steven; Verma, Mayank; Rayner, Samuel [Stem Cell Institute, University of Minnesota, Room 2-216, MTRF, 2001 6th St. SE, Minneapolis, MN 55455 (United States)] [Stem Cell Institute, University of Minnesota, Room 2-216, MTRF, 2001 6th St. SE, Minneapolis, MN 55455 (United States); Asakura, Atsushi, E-mail: asakura@umn.edu [Stem Cell Institute, University of Minnesota, Room 2-216, MTRF, 2001 6th St. SE, Minneapolis, MN 55455 (United States)] [Stem Cell Institute, University of Minnesota, Room 2-216, MTRF, 2001 6th St. SE, Minneapolis, MN 55455 (United States); Kikyo, Nobuaki, E-mail: kikyo001@umn.edu [Stem Cell Institute, University of Minnesota, Room 2-216, MTRF, 2001 6th St. SE, Minneapolis, MN 55455 (United States)] [Stem Cell Institute, University of Minnesota, Room 2-216, MTRF, 2001 6th St. SE, Minneapolis, MN 55455 (United States)

    2010-01-01

    Nucleostemin (NS) is a nucleolar protein abundantly expressed in a variety of proliferating cells and undifferentiated cells. Its known functions include cell cycle regulation and the control of pre-rRNA processing. It also has been proposed that NS has an additional role in undifferentiated cells due to its downregulation during stem cell differentiation and its upregulation during tissue regeneration. Here, however, we demonstrate that skeletal muscle cell differentiation has a unique expression profile of NS in that it is continuously expressed during differentiation. NS was expressed at similar levels in non-proliferating muscle stem cells (satellite cells), rapidly proliferating precursor cells (myoblasts) and post-mitotic terminally differentiated cells (myotubes and myofibers). The sustained expression of NS during terminal differentiation is necessary to support increased protein synthesis during this process. Downregulation of NS inhibited differentiation of myoblasts to myotubes, accompanied by striking downregulation of key myogenic transcription factors, such as myogenin and MyoD. In contrast, upregulation of NS inhibited proliferation and promoted muscle differentiation in a p53-dependent manner. Our findings provide evidence that NS has an unexpected role in post-mitotic terminal differentiation. Importantly, these findings also indicate that, contrary to suggestions in the literature, the expression of NS cannot always be used as a reliable indicator for undifferentiated cells or proliferating cells.

  12. Weighting Features

    Microsoft Academic Search

    Dietrich Wettschereck I; David W. Aha

    1995-01-01

    . Many case-based reasoning algorithms retrieve cases using aderivative of the k-nearest neighbor (k-NN) classifier, whose similarityfunction is sensitive to irrelevant, interacting, and noisy features. Manyproposed methods for reducing this sensitivity parameterize k-NN's similarityfunction with feature weights. We focus on methods that automaticallyassign weight settings using little or no domain-specific knowledge.Our goal is to predict the relative capabilities of these

  13. Does vitamin D status correlate with clinical and biochemical features of polycystic ovarysyndrome in high school girls?

    PubMed Central

    Ghadimi, Reza; Esmaeilzadeh, Sedighe; Firoozpour, Marmar; Ahmadi, Asal

    2014-01-01

    Background: Prevalence of polycystic ovary syndrome (PCOs) is increasing particularly among the female adolescents and young women. It has been hypothesized that disturbance in calcium and vitamin-D metabolism may affect the symptoms of this syndrome. This study was designed to investigate the relationship between vitamin-D and calcium with metabolic parameters and other characteristics of the PCOs. Methods: The study included 192 Iranian girls (16-20 years old), of whom 104 had PCOs and 88 were non-PCOs controls. Serum 25(OH) D and calcium level was measured. Anthropometric components, endocrine, metabolic components and insulin resistance were determined in PCOs subjects. Results: Mean 25 (OH) D was significantly lower in cases (9.7±4.8) than controls (12.3±11.9) but calcium level did not differ between the two groups (9.3±0.3 vs 9.4±0.4). No significant correlations were found between 25(OH) D levels and lipid profile, FBS, fasting insulin endocrine parameters such as testosterone, free testosterone, FSH, LH, and prolactin. Conclusion: Although hypovitamionos D was common is PCOs but did not correlate with clinical features or complications of obesity and insulin resistance PCO like severity of syndrome between vitamin-D deficiency and its severity with some features and complications of PCOs including obesity, insulin resistance. PMID:25489430

  14. High-velocity ultraviolet iron, silicon, oxygen, and sulfur absorption features associated with the remnant of SN 1006

    NASA Technical Reports Server (NTRS)

    Fesen, Robert A.; Wu, Chi-Chao; Leventhal, Marvin; Hamilton, Andrew J. S.

    1988-01-01

    New low-dispersion IUE spectra of a faint sdOb star located in a direction near the center of the SN 1006 remnant are presented. The UV spectrum of the star exhibits several strong absorption features which are uncharacteristic of its optical sdOB star classification. The identification by Wu et al. (1983) of very broad absorption features at 1610, 2370, 2600 A as Fe II gas associated with the SN 1006 remnant is supported. The observed Fe II line profiles indicate a concentration of Fe(+) toward the remnant's center with a radial velocity range on the order of + or - 5000 km/s. Strong absorption lines at 1281, 1331, and 1420 A are interpreted as originating from clumps of O-, Si- and S-rich ejecta with central radial velocities in the range 5000-6500 km/s. The presence in the SN 1006 remnant of an expanding sphere of iron-rich ejecta interior to O-, Si-, and S-rich clumps of ejecta having velocities over the maximum seen for the Fe II absorbing gas is consistent with type Ia Sn observations and carbon deflagration models.

  15. Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death.

    PubMed

    Chen, H; Huang, S; Han, X; Zhang, J; Shan, C; Tsang, Y H; Ma, H T; Poon, R Y C

    2014-01-01

    Many mitotic kinases are both critical for maintaining genome stability and are important targets for anticancer therapies. We provide evidence that SIK3 (salt-inducible kinase 3), an AMP-activated protein kinase-related kinase, is important for mitosis to occur properly in mammalian cells. Downregulation of SIK3 resulted in an extension of mitosis in both mouse and human cells but did not affect the DNA damage checkpoint. Time-lapse microscopy and other approaches indicated that mitotic exit but not mitotic entry was delayed. Although repression of SIK3 alone simply delayed mitotic exit, it was able to sensitize cells to various antimitotic chemicals. Both mitotic arrest and cell death caused by spindle poisons were enhanced after SIK3 depletion. Likewise, the antimitotic effects due to pharmacological inhibition of mitotic kinases including Aurora A, Aurora B, and polo-like kinase 1 were enhanced in the absence of SIK3. Finally, in addition to promoting the sensitivity of a small-molecule inhibitor of the mitotic kinesin Eg5, SIK3 depletion was able to overcome cells that developed drug resistance. These results establish the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. PMID:24743732

  16. Mitotic Accumulation of Dimethylated Lysine 79 of Histone H3 Is Important for Maintaining Genome Integrity During Mitosis in Human Cells

    PubMed Central

    Guppy, Brent J.; McManus, Kirk J.

    2015-01-01

    The loss of genome stability is an early event that drives the development and progression of virtually all tumor types. Recent studies have revealed that certain histone post-translational modifications exhibit dynamic and global increases in abundance that coincide with mitosis and exhibit essential roles in maintaining genomic stability. Histone H2B ubiquitination at lysine 120 (H2Bub1) is regulated by RNF20, an E3 ubiquitin ligase that is altered in many tumor types. Through an evolutionarily conserved trans-histone pathway, H2Bub1 is an essential prerequisite for subsequent downstream dimethylation events at lysines 4 (H3K4me2) and 79 (H3K79me2) of histone H3. Although the role that RNF20 plays in tumorigenesis has garnered much attention, the downstream components of the trans-histone pathway, H3K4me2 and H3K79me2, and their potential contributions to genome stability remain largely overlooked. In this study, we employ single-cell imaging and biochemical approaches to investigate the spatial and temporal patterning of RNF20, H2Bub1, H3K4me2, and H3K79me2 throughout the cell cycle, with a particular focus on mitosis. We show that H2Bub1, H3K4me2, and H3K79me2 exhibit distinct temporal progression patterns throughout the cell cycle. Most notably, we demonstrate that H3K79me2 is a highly dynamic histone post-translational modification that reaches maximal abundance during mitosis in an H2Bub1-independent manner. Using RNAi and chemical genetic approaches, we identify DOT1L as a histone methyltransferase required for the mitotic-associated increases in H3K79me2. We also demonstrate that the loss of mitotic H3K79me2 levels correlates with increases in chromosome numbers and increases in mitotic defects. Collectively, these data suggest that H3K79me2 dynamics during mitosis are normally required to maintain genome stability and further implicate the loss of H3K79me2 during mitosis as a pathogenic event that contributes to the development and progression of tumors. PMID:25533199

  17. Embryos of Robertsonian Translocation Carriers Exhibit a Mitotic Interchromosomal Effect That Enhances Genetic Instability during Early Development

    PubMed Central

    Alfarawati, Samer; Fragouli, Elpida; Colls, Pere; Wells, Dagan

    2012-01-01

    Balanced chromosomal rearrangements represent one of the most common forms of genetic abnormality affecting approximately 1 in every 500 (0.2%) individuals. Difficulties processing the abnormal chromosomes during meiosis lead to an elevated risk of chromosomally abnormal gametes, resulting in high rates of miscarriage and/or children with congenital abnormalities. It has also been suggested that the presence of chromosome rearrangements may also cause an increase in aneuploidy affecting structurally normal chromosomes, due to disruption of chromosome alignment on the spindle or disturbance of other factors related to meiotic chromosome segregation. The existence of such a phenomenon (an inter-chromosomal effect—ICE) remains controversial, with different studies presenting contradictory data. The current investigation aimed to demonstrate conclusively whether an ICE truly exists. For this purpose a comprehensive chromosome screening technique, optimized for analysis of minute amounts of tissue, was applied to a unique collection of samples consisting of 283 oocytes and early embryos derived from 44 patients carrying chromosome rearrangements. A further 5,078 oocytes and embryos, derived from chromosomally normal individuals of identical age, provided a robust control group for comparative analysis. A highly significant (P?=?0.0002) increase in the rate of malsegregation affecting structurally normal chromosomes was observed in association with Robertsonian translocations. Surprisingly, the ICE was clearly detected in early embryos from female carriers, but not in oocytes, indicating the possibility of mitotic rather than the previously suggested meiotic origin. These findings have implications for our understanding of genetic stability during preimplantation development and are of clinical relevance for patients carrying a Robertsonian translocation. The results are also pertinent to other situations when cellular mechanisms for maintaining genetic fidelity are relaxed and chromosome rearrangements are present (e.g. in tumors displaying chromosomal instability). PMID:23133396

  18. Depletion of the protein kinase VRK1 disrupts nuclear envelope morphology and leads to BAF retention on mitotic chromosomes.

    PubMed

    Molitor, Tyler P; Traktman, Paula

    2014-03-01

    Barrier to autointegration factor (BAF), which is encoded by the BANF1 gene, binds with high-affinity to double-stranded DNA and LEM domain-containing proteins at the nuclear periphery. A BANF1 mutation has recently been associated with a novel human progeria syndrome, and cells from these patients have aberrant nuclear envelopes. The interactions of BAF with its DNA- and protein-binding partners are known to be regulated by phosphorylation, and previously we validated BAF as a highly efficient substrate for the VRK1 protein kinase. Here we show that depletion of VRK1 in MCF10a and MDA-MB-231 cells results in aberrant nuclear architecture. The immobile fraction of green fluorescent protein (GFP)-BAF at the nuclear envelope (NE) is elevated, suggesting that prolonged interactions of BAF with its binding partners is likely responsible for the aberrant NE architecture. Because detachment of BAF from its binding partners is associated with NE disassembly, we performed live-imaging analysis of control and VRK1-depleted cells to visualize GFP-BAF dynamics during mitosis. In the absence of VRK1, BAF does not disperse but instead remains chromosome bound from the onset of mitosis. VRK1 depletion also increases the number of anaphase bridges and multipolar spindles. Thus phosphorylation of BAF by VRK1 is essential both for normal NE architecture and proper dynamics of BAF-chromosome interactions during mitosis. These results are consistent with previous studies of the VRK/BAF signaling axis in Caenorhabditis elegans and Drosophila melanogaster and validate VRK1 as a key regulator of NE architecture and mitotic chromosome dynamics in mammalian cells. PMID:24430874

  19. Using high resolution IKONOS imagery and feature-based classifiers to automate a classification of savanna woodlands 

    E-print Network

    Michelakis, Dimitrios

    2008-12-05

    High resolution remote sensing imagery offers one possible means to discriminate the constituent land cover components within savanna woodlands, with differing economic potential and ability to sequester carbon. Recent work on tropical savannas...

  20. Cyto-histopathological and outcome features of the prepuce squamous cell carcinoma of a mixed breed dog

    PubMed Central

    2014-01-01

    Abstract Background Squamous cell carcinomas (SCCs) are uncommon, high-grade tumors, predominantly composed of round cells in the prepuce. The aim of this study is to better define the clinicopathologic features of this neoplasm. Case report We conducted cyto-histopathologic analysis on the manifestations of the prepuce SCC by H & E staining in a terrier mix dog. Grossly, tumor was large, multiple erythematous patch, and ulcerated masses frequently affecting the prepuce and deeply invading to distal prepuce out from the ventro-lateral of penis and the tumor covered by a necrotic discharge. Cytological evaluation of fine-needle aspirates from the cutaneous mass from the prepuce comprised of round nuclei, coarse chromatin pattern, distinct nucleoli and nuclear pleomorphism. Furthermore, the neoplastic cells were pleomorphic, round to caudate in shape, exhibiting prominent anisokaryosis and anisocytosis with rare mitotic features. Microscopically, the lesions were predominantly composed of atypical round cells disposed in interlacing fascicles. Frequent findings include keratin formation, horn pearls, mitoses and cellular atypia. The cells showed distinct borders, ranged from polygonal to round or elongate and had moderate amounts of eosinophilic cytoplasm. Conclusion The histopathologic features coupled with the cytopathology findings led to a diagnosis of squamous cell carcinoma. To the authors’ knowledge, this is the first time that multiple erythematous plaques have undergone malignant transformation in a terrier mix dog. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5748771971272873 PMID:24903567