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1

Classification of mitotic figures with convolutional neural networks and seeded blob features  

PubMed Central

Background: The mitotic figure recognition contest at the 2012 International Conference on Pattern Recognition (ICPR) challenges a system to identify all mitotic figures in a region of interest of hematoxylin and eosin stained tissue, using each of three scanners (Aperio, Hamamatsu, and multispectral). Methods: Our approach combines manually designed nuclear features with the learned features extracted by convolutional neural networks (CNN). The nuclear features capture color, texture, and shape information of segmented regions around a nucleus. The use of a CNN handles the variety of appearances of mitotic figures and decreases sensitivity to the manually crafted features and thresholds. Results: On the test set provided by the contest, the trained system achieves F1 scores up to 0.659 on color scanners and 0.589 on multispectral scanner. Conclusions: We demonstrate a powerful technique combining segmentation-based features with CNN, identifying the majority of mitotic figures with a fair precision. Further, we show that the approach accommodates information from the additional focal planes and spectral bands from a multi-spectral scanner without major redesign. PMID:23858384

Malon, Christopher D.; Cosatto, Eric

2013-01-01

2

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

PubMed

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

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

2014-06-01

3

High-Resolution Mapping of Two Types of Spontaneous Mitotic Gene Conversion Events in Saccharomyces cerevisiae  

PubMed Central

Gene conversions and crossovers are related products of the repair of double-stranded DNA breaks by homologous recombination. Most previous studies of mitotic gene conversion events have been restricted to measuring conversion tracts that are <5 kb. Using a genetic assay in which the lengths of very long gene conversion tracts can be measured, we detected two types of conversions: those with a median size of ?6 kb and those with a median size of >50 kb. The unusually long tracts are initiated at a naturally occurring recombination hotspot formed by two inverted Ty elements. We suggest that these long gene conversion events may be generated by a mechanism (break-induced replication or repair of a double-stranded DNA gap) different from the short conversion tracts that likely reflect heteroduplex formation followed by DNA mismatch repair. Both the short and long mitotic conversion tracts are considerably longer than those observed in meiosis. Since mitotic crossovers in a diploid can result in a heterozygous recessive deleterious mutation becoming homozygous, it has been suggested that the repair of DNA breaks by mitotic recombination involves gene conversion events that are unassociated with crossing over. In contrast to this prediction, we found that ?40% of the conversion tracts are associated with crossovers. Spontaneous mitotic crossover events in yeast are frequent enough to be an important factor in genome evolution. PMID:24990991

Yim, Eunice; O'Connell, Karen E.; St. Charles, Jordan; Petes, Thomas D.

2014-01-01

4

Inhibitory effect of ethidium bromide on mitotic chromosome condensation and its application to high-resolution chromosome banding  

Microsoft Academic Search

Ethidium bromide (EB) is known to intercalate between stacked base pairs without specific base-pair preference. Its use in cultured human lymphocytes and Burkitt’s lymphoma cells resulted in the accumulation of cells in prophase and prometaphase stages. Inhibition of mitotic chromosome condensation as a possible mechanism involved in this phenomenon is discussed. A simple method for obtaining high-resolution banding patterns on

T. Ikeuchi

1984-01-01

5

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

PubMed Central

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

Yin, Yi; Petes, Thomas D.

2013-01-01

6

High-Resolution Mapping of Spontaneous Mitotic Recombination Hotspots on the 1.1 Mb Arm of Yeast Chromosome IV  

PubMed Central

Although homologous recombination is an important pathway for the repair of double-stranded DNA breaks in mitotically dividing eukaryotic cells, these events can also have negative consequences, such as loss of heterozygosity (LOH) of deleterious mutations. We mapped about 140 spontaneous reciprocal crossovers on the right arm of the yeast chromosome IV using single-nucleotide-polymorphism (SNP) microarrays. Our mapping and subsequent experiments demonstrate that inverted repeats of Ty retrotransposable elements are mitotic recombination hotspots. We found that the mitotic recombination maps on the two homologs were substantially different and were unrelated to meiotic recombination maps. Additionally, about 70% of the DNA lesions that result in LOH are likely generated during G1 of the cell cycle and repaired during S or G2. We also show that different genetic elements are associated with reciprocal crossover conversion tracts depending on the cell cycle timing of the initiating DSB. PMID:23593029

St. Charles, Jordan; Petes, Thomas D.

2013-01-01

7

High diversity and widespread occurrence of mitotic spore mats in ectomycorrhizal Pezizales.  

PubMed

Fungal mitospores may function as dispersal units and/ or spermatia and thus play a role in distribution and/or mating of species that produce them. Mitospore production in ectomycorrhizal (EcM) Pezizales is rarely reported, but here we document mitospore production by a high diversity of EcM Pezizales on three continents, in both hemispheres. We sequenced the internal transcribed spacer (ITS) and partial large subunit (LSU) nuclear rDNA from 292 spore mats (visible mitospore clumps) collected in Argentina, Chile, China, Mexico and the USA between 2009 and 2012. We collated spore mat ITS sequences with 105 fruit body and 47 EcM root sequences to generate operational taxonomic units (OTUs). Phylogenetic inferences were made through analyses of both molecular data sets. A total of 48 OTUs from spore mats represented six independent EcM Pezizales lineages and included truffles and cup fungi. Three clades of seven OTUs have no known meiospore stage. Mitospores failed to germinate on sterile media, or form ectomycorrhizas on Quercus, Pinus and Populus seedlings, consistent with a hypothesized role of spermatia. The broad geographic range, high frequency and phylogenetic diversity of spore mats produced by EcM Pezizales suggests that a mitospore stage is important for many species in this group in terms of mating, reproduction and/or dispersal. PMID:23205556

Healy, R A; Smith, M E; Bonito, G M; Pfister, D H; Ge, Z-W; Guevara, G G; Williams, G; Stafford, K; Kumar, L; Lee, T; Hobart, C; Trappe, J; Vilgalys, R; McLaughlin, D J

2013-03-01

8

Iterative feature removal yields highly discriminative pathways  

PubMed Central

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

2013-01-01

9

P2P-R protein overexpression restricts mitotic progression at prometaphase and promotes mitotic apoptosis.  

PubMed

Mitotic cells show a tenfold increase in immunoreactive P2P-R protein. During mitosis, the distribution of P2P-R protein also changes from a primary nucleolar localization in interphase cells to the periphery of chromosome in mitotic cells. These findings suggest that P2P-R might serve a functional role in mitosis. To test this possibility, human Saos2 cells were stably transfected with P2P-R DNA constructs and the biological effects of P2P-R overexpression were evaluated. Overexpression of near full-length P2P-R was found to have paradoxical effects on the relationship between proliferation and mitosis in the nine Saos2 cell clones that were studied. A significant repression in the population doubling rates was observed in all nine clones even though a significant increase in the frequency of easily detached cells with a mitotic morphology was apparent. Flow cytometric analysis confirmed that greater than two thirds of the cells with a mitotic morphology had a 4n DNA content. Confocal microscopy further established that 85% of the mitotic cell population had prometaphase characteristics suggesting that P2P-R overexpression restricts mitotic progression at prometaphase. Many cells with a mitotic morphology also showed signs of apoptosis with prominent cell surface blebs. Confocal microscopy confirmed that 25-40% of such mitotic cells were apoptotic with chromosomal abnormalities and cell surface blebbing. In association with mitotic apoptosis, P2P-R protein appears to dissociate from the periphery of chromosomes and localize in the cytoplasm and in cell surface blebs. The presence of P2P-R in cell surface blebs was confirmed by analysis of highly enriched populations of apoptotic cell surface blebs wherein Western blotting documented the presence of 250 kDa P2P-R. These results therefore suggest that P2P-R overexpression promotes both prometaphase arrest in mitosis and mitotic apoptosis. PMID:12384997

Gao, Sizhi; Scott, Robert E

2002-11-01

10

Continued Stabilization of the Nuclear Higher-Order Structure of Post-Mitotic Neurons In Vivo  

PubMed Central

Background Cellular terminal differentiation (TD) correlates with a permanent exit from the cell cycle and so TD cells become stably post-mitotic. However, TD cells express the molecular machinery necessary for cell proliferation that can be reactivated by experimental manipulation, yet it has not been reported the stable proliferation of any type of reactivated TD cells. Neurons become post-mitotic after leaving the ventricular zone. When neurons are forced to reenter the cell cycle they invariably undergo cell death. Wider evidence indicates that the post-mitotic state cannot solely depend on gene products acting in trans, otherwise mutations in the corresponding genes may lead to reentry and completion of the cell cycle in TD cells, but this has not been observed. In the interphase, nuclear DNA of metazoan cells is organized in supercoiled loops anchored to a nuclear nuclear matrix (NM). The DNA-NM interactions define a higher-order structure in the cell nucleus (NHOS). We have previously compared the NHOS of aged rat hepatocytes with that of early post-mitotic rat neurons and our results indicated that a very stable NHOS is a common feature of both senescent and post-mitotic cells in vivo. Principal Findings In the present work we compared the NHOS in rat neurons from different post-natal ages. Our results show that the trend towards further stabilization of the NHOS in neurons continues throughout post-natal life. This phenomenon occurs in absence of overt changes in the post-mitotic state and transcriptional activity of neurons, suggesting that it is independent of functional constraints. Conclusions Apparently the continued stabilization of the NHOS as a function of time is basically determined by thermodynamic and structural constraints. We discuss how the resulting highly stable NHOS of neurons may be the structural, non-genetic basis of their permanent and irreversible post-mitotic state. PMID:21731716

Alva-Medina, Janeth; Maya-Mendoza, Apolinar; Dent, Myrna A. R.; Aranda-Anzaldo, Armando

2011-01-01

11

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

PubMed Central

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

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

2012-01-01

12

Mitotic chromosome condensation in vertebrates  

SciTech Connect

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

Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

2012-07-15

13

Mitotic illegitimate recombination is a mechanism for novel changes in high-molecular-weight glutenin subunits in wheat-rye hybrids.  

PubMed

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 F(1) and F(2) 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 F(1) and 22% of 36 F(2) 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 F(1) and F(2) 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

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

2011-01-01

14

High-dimensional feature selection by feature-wise kernelized Lasso.  

PubMed

The goal of supervised feature selection is to find a subset of input features that are responsible for predicting output values. The least absolute shrinkage and selection operator (Lasso) allows computationally efficient feature selection based on linear dependency between input features and output values. In this letter, we consider a feature-wise kernelized Lasso for capturing nonlinear input-output dependency. We first show that with particular choices of kernel functions, nonredundant features with strong statistical dependence on output values can be found in terms of kernel-based independence measures such as the Hilbert-Schmidt independence criterion. We then show that the globally optimal solution can be efficiently computed; this makes the approach scalable to high-dimensional problems. The effectiveness of the proposed method is demonstrated through feature selection experiments for classification and regression with thousands of features. PMID:24102126

Yamada, Makoto; Jitkrittum, Wittawat; Sigal, Leonid; Xing, Eric P; Sugiyama, Masashi

2014-01-01

15

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

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

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

16

A new genetic method for isolating functionally interacting genes: high plo1(+)-dependent mutants and their suppressors define genes in mitotic and septation pathways in fission yeast.  

PubMed Central

We describe a general genetic method to identify genes encoding proteins that functionally interact with and/or are good candidates for downstream targets of a particular gene product. The screen identifies mutants whose growth depends on high levels of expression of that gene. We apply this to the plo1(+) gene that encodes a fission yeast homologue of the polo-like kinases. plo1(+) regulates both spindle formation and septation. We have isolated 17 high plo1(+)-dependent (pld) mutants that show defects in mitosis or septation. Three mutants show a mitotic arrest phenotype. Among the 14 pld mutants with septation defects, 12 mapped to known loci: cdc7, cdc15, cdc11 spg1, and sid2. One of the pld mutants, cdc7-PD1, was selected for suppressor analysis. As multicopy suppressors, we isolated four known genes involved in septation in fission yeast: spg1(+), sce3(+), cdc8(+), and rho1(+), and two previously uncharacterized genes, mpd1(+) and mpd2(+). mpd1(+) exhibits high homology to phosphatidylinositol 4-phosphate 5-kinase, while mpd2(+) resembles Saccharomyces cerevisiae SMY2; both proteins are involved in the regulation of actin-mediated processes. As chromosomal suppressors of cdc7-PD1, we isolated mutations of cdc16 that resulted in multiseptation without nuclear division. cdc16(+), dma1(+), byr3(+), byr4(+) and a truncated form of the cdc7 gene were isolated by complementation of one of these cdc16 mutations. These results demonstrate that screening for high dose-dependent mutants and their suppressors is an effective approach to identify functionally interacting genes. PMID:10924454

Cullen, C F; May, K M; Hagan, I M; Glover, D M; Ohkura, H

2000-01-01

17

Mitotic Spindle Form and Function  

PubMed Central

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

Winey, Mark; Bloom, Kerry

2012-01-01

18

Energy Conservation Featured in Illinois High School  

ERIC Educational Resources Information Center

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)

Modern Schools, 1976

1976-01-01

19

Phosphatases: providing safe passage through mitotic exit  

Microsoft Academic Search

The mitosis-to-interphase transition involves dramatic cellular reorganization from a state that supports chromosome segregation to a state that complies with all functions of an interphase cell. This process, termed mitotic exit, depends on the removal of mitotic phosphorylations from a broad range of substrates. Mitotic exit regulation involves inactivation of mitotic kinases and activation of counteracting protein phosphatases. The key

Claudia Wurzenberger; Daniel W. Gerlich

2011-01-01

20

Micromechanical studies of mitotic chromosomes  

Microsoft Academic Search

Mitotic chromosomes respond elastically to forces in the nanonewton range, a property important to transduction of stresses\\u000a used as mechanical regulatory signals during cell division. In addition to being important biologically, chromosome elasticity\\u000a can be used as a tool for investigating the folding of chromatin. This paper reviews experiments studying stretching and bending\\u000a stiffness of mitotic chromosomes, plus experiments where

John F. Marko

2008-01-01

21

Meiotic and Mitotic Recombination in Meiosis  

PubMed Central

Meiotic crossovers facilitate the segregation of homologous chromosomes and increase genetic diversity. The formation of meiotic crossovers was previously posited to occur via two pathways, with the relative use of each pathway varying between organisms; however, this paradigm could not explain all crossovers, and many of the key proteins involved were unidentified. Recent studies that identify some of these proteins reinforce and expand the model of two meiotic crossover pathways. The results provide novel insights into the evolutionary origins of the pathways, suggesting that one is similar to a mitotic DNA repair pathway and the other evolved to incorporate special features unique to meiosis. PMID:23733849

Kohl, Kathryn P.; Sekelsky, Jeff

2013-01-01

22

High-resolution Urban Image Classification Using Extended Features  

SciTech Connect

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.

Vatsavai, Raju [ORNL] [ORNL

2011-01-01

23

Feature selection in high dimensional regression problems for genomics  

E-print Network

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

Paris-Sud XI, Université de

24

Highly comparative, feature-based time-series classification  

E-print Network

A highly comparative, feature-based approach to time series classification is introduced that uses an extensive database of algorithms to extract thousands of interpretable features from time series. These features are derived from across the scientific time-series analysis literature, and include summaries of time series in terms of their correlation structure, distribution, entropy, stationarity, scaling properties, and fits to a range of time-series models. After computing thousands of features for each time series in a training set, those that are most informative of the class structure are selected using greedy forward feature selection with a linear classifier. The resulting feature-based classifiers automatically learn the differences between classes using a reduced number of time-series properties, and circumvent the need to calculate distances between time series. Representing time series in this way results in orders of magnitude of dimensionality reduction, allowing the method to perform well on ve...

Fulcher, Ben D

2014-01-01

25

Unsupervised Feature Learning for High-Resolution Satellite Image Classification  

SciTech Connect

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.

Cheriyadat, Anil M [ORNL

2013-01-01

26

OVARIAN LOW-GRADE AND HIGH-GRADE SEROUS CARCINOMA: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems  

PubMed Central

Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937

Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.

2009-01-01

27

Mitotically active microglandular hyperplasia of the cervix: a case series with implications for the differential diagnosis.  

PubMed

Microglandular hyperplasia (MGH) is a benign proliferation of endocervical glands with relatively uniform columnar or cuboidal nuclei, and rare to absent mitoses. Endometrial adenocarcinomas with mucinous differentiation or a microglandular pattern can closely mimic MGH, often resulting in a diagnostic dilemma in small biopsy specimens. Rare unusual morphologic features-mild to moderate nuclear atypia, solid or reticular growth pattern, hobnail and signet ring cells-have been previously reported in MGH. We present 9 cases of unusual, mitotically active-between 5 and 11 mitotic figures per 10 HPF-MGH, all of which presented as endocervical polyps and had morphologic features otherwise typical of MGH. The patients' age ranged between 35 and 56 yr, 2 patients were postmenopausal. High-risk human papillomavirus status was available in 7 patients, all of which were negative. The Ki-67 proliferation index ranged between 1% and 15%, and all cases were negative for p16, carcinoembryonic antigen, and vimentin immunostains. The clinical follow-up ranged from 3 to 76.2 mo, with a median of 40.7 mo, all patients were doing well without evidence of endocervical or endometrial malignancy. In summary, this case series documents the presence of rare cases of MGH demonstrating significant mitotic activity (up to 11/10 HPF) without a negative impact on the clinical prognosis. Mitotic activity alone should be interpreted with caution in small biopsy specimens with microglandular growth pattern. Immunohistochemical stains, especially p16, carcinoembryonic antigen, and vimentin, may be helpful-in addition to the patient's clinical history and human papillomavirus status to rule out endocervical or endometrial malignancy. PMID:25083971

Abi-Raad, Rita; Alomari, Ahmed; Hui, Pei; Buza, Natalia

2014-09-01

28

High-speed digital signal normalization for feature identification  

NASA Technical Reports Server (NTRS)

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

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

1983-01-01

29

Object Classification and Detection in High Dimensional Feature Space  

E-print Network

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

Bey, Isabelle

30

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

PubMed Central

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

Govindaraghavan, Meera; Lad, Alisha A.

2014-01-01

31

A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor  

PubMed Central

The inactivation of BRCA2, a suppressor of breast, ovarian and other epithelial cancers, triggers instability in chromosome structure and number, which are thought to arise from defects in DNA recombination and mitotic cell division, respectively. Human BRCA2 controls DNA recombination via eight BRC repeats, evolutionarily conserved motifs of ?35 residues, that interact directly with the recombinase RAD51. How BRCA2 controls mitotic cell division is debated. Several studies by different groups report that BRCA2 deficiency affects cytokinesis. Moreover, its interaction with HMG20b, a protein of uncertain function containing a promiscuous DNA-binding domain and kinesin-like coiled coils, has been implicated in the G2–M transition. We show here that HMG20b depletion by RNA interference disturbs the completion of cell division, suggesting a novel function for HMG20b. In vitro, HMG20b binds directly to the BRC repeats of BRCA2, and exhibits the highest affinity for BRC5, a motif that binds poorly to RAD51. Conversely, the BRC4 repeat binds strongly to RAD51, but not to HMG20b. In vivo, BRC5 overexpression inhibits the BRCA2–HMG20b interaction, recapitulating defects in the completion of cell division provoked by HMG20b depletion. In contrast, BRC4 inhibits the BRCA2–RAD51 interaction and the assembly of RAD51 at sites of DNA damage, but not the completion of cell division. Our findings suggest that a novel function for HMG20b in cytokinesis is regulated by its interaction with the BRC repeats of BRCA2, and separate this unexpected function for the BRC repeats from their known activity in DNA recombination. We propose that divergent tumor-suppressive pathways regulating chromosome segregation as well as chromosome structure may be governed by the conserved BRC motifs in BRCA2. PMID:21399666

Lee, M; Daniels, M J; Garnett, M J; Venkitaraman, A R

2011-01-01

32

A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor.  

PubMed

The inactivation of BRCA2, a suppressor of breast, ovarian and other epithelial cancers, triggers instability in chromosome structure and number, which are thought to arise from defects in DNA recombination and mitotic cell division, respectively. Human BRCA2 controls DNA recombination via eight BRC repeats, evolutionarily conserved motifs of ?35 residues, that interact directly with the recombinase RAD51. How BRCA2 controls mitotic cell division is debated. Several studies by different groups report that BRCA2 deficiency affects cytokinesis. Moreover, its interaction with HMG20b, a protein of uncertain function containing a promiscuous DNA-binding domain and kinesin-like coiled coils, has been implicated in the G2-M transition. We show here that HMG20b depletion by RNA interference disturbs the completion of cell division, suggesting a novel function for HMG20b. In vitro, HMG20b binds directly to the BRC repeats of BRCA2, and exhibits the highest affinity for BRC5, a motif that binds poorly to RAD51. Conversely, the BRC4 repeat binds strongly to RAD51, but not to HMG20b. In vivo, BRC5 overexpression inhibits the BRCA2-HMG20b interaction, recapitulating defects in the completion of cell division provoked by HMG20b depletion. In contrast, BRC4 inhibits the BRCA2-RAD51 interaction and the assembly of RAD51 at sites of DNA damage, but not the completion of cell division. Our findings suggest that a novel function for HMG20b in cytokinesis is regulated by its interaction with the BRC repeats of BRCA2, and separate this unexpected function for the BRC repeats from their known activity in DNA recombination. We propose that divergent tumor-suppressive pathways regulating chromosome segregation as well as chromosome structure may be governed by the conserved BRC motifs in BRCA2. PMID:21399666

Lee, M; Daniels, M J; Garnett, M J; Venkitaraman, A R

2011-07-28

33

EGF Induced Centrosome Separation Promotes Mitotic Progression and Cell Survival  

PubMed Central

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

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

2014-01-01

34

Loops determine the mechanical properties of mitotic chromosomes  

NASA Astrophysics Data System (ADS)

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.

Zhang, Yang; Heermann, Dieter W.

2013-03-01

35

Features of Nearest Neighbors Distances in High-Dimensional Space  

Microsoft Academic Search

Methods of nearest neighbors are essential in wide range of applications where it is necessary to estimate probability density (e.g. Bayes's classifier, problems of searching in large databases). This paper contemplates on features of distribution of nearest neighbors' distances in high-dimensional spaces. It shows that for uniform distribution of points in n-dimensional Euclidean space the distribution of the distance of

Marcel Jiina

36

Fusing high- and low-level features for speaker recognition  

Microsoft Academic Search

The area of automatic speaker recognition has been dominated by systems using only short-term, low-level acoustic information, such as cepstral features. While these systems have produced low error rates, they ignore higher levels of information beyond low-level acoustics that convey speaker information. Recently published works have demonstrated that such high-level information can be used successfully in automatic speaker recognition systems

Joseph P. Campbell; Douglas A. Reynolds; Robert B. Dunn

2003-01-01

37

Efficient Learning and Feature Selection in High-Dimensional Regression  

Microsoft Academic Search

We present a novel algorithm for efficient learning and feature selection in high-dimensional regression problems. We arrive at this model through a modification of the standard regression model, enabling us to derive a probabilistic version of the well-known statistical regression technique of backfitting. Using the expectation-maximization algorithm, along with variational approximation methods to overcome intractability, we extend our algorithm to

Jo-Anne Ting; Aaron D'Souza; Sethu Vijayakumar; Stefan Schaal

2010-01-01

38

Prognostic value of mitotic index and Bcl2 expression in male breast cancer.  

PubMed

The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic value. Previous papers on Bcl2 expression in MBC were equivocal, and the prognostic value of Bcl2 combined with mitotic index has not been studied in MBC. The aim of the present study was therefore to investigate the prognostic value of Bcl2 in combination with mitotic index in MBC. Immunohistochemical staining for Bcl2 was performed on tissue microarrays of a total of 151 male breast cancer cases. Mitotic index was scored. The prognostic value of Bcl2 expression and Bcl2/mitotic index combinations was evaluated studying their correlations with clinicopathologic features and their prediction of survival. The vast majority of MBC (94%) showed Bcl2 expression, more frequently than previously described for FBC. Bcl2 expression had no significant associations with clinicopathologic features such as tumor size, mitotic count and grade. In univariate survival analysis, Bcl2 had no prognostic value, and showed no additional prognostic value to tumor size and histological grade in Cox regression. In addition, the Bcl2/mitotic index combination as opposed to FBC did not predict survival in MBC. In conclusion, Bcl2 expression is common in MBC, but is not associated with major clinicopathologic features and, in contrast to FBC, does not seem to have prognostic value, also when combined with mitotic index. PMID:23573235

Lacle, Miangela M; van der Pol, Carmen; Witkamp, Arjen; van der Wall, Elsken; van Diest, Paul J

2013-01-01

39

Quantifying mitotic chromosome dynamics and positioning.  

PubMed

The proper organization and segregation of chromosomes during cell division is essential to the preservation of genomic integrity. To understand the mechanisms that spatially control the arrangement and dynamics of mitotic chromosomes requires imaging assays to quantitatively resolve their positions and movements. Here, we will discuss analytical approaches to investigate the position-dependent control of mitotic chromosomes in cultured cells. These methods can be used to dissect the specific contributions of mitotic proteins to the molecular control of chromosome dynamics. PMID:24683081

Bissonette, Samantha; Stumpff, Jason

2014-10-01

40

Quantification of upland thermokarst features with high resolution remote sensing  

NASA Astrophysics Data System (ADS)

Climate-induced changes to permafrost are altering high latitude landscapes in ways that could increase the vulnerability of the vast soil carbon pools of the region. Permafrost thaw is temporally dynamic and spatially heterogeneous because, in addition to the thickening of the active layer, localized thermokarst features form when ice-rich permafrost thaws and the ground subsides. Thermokarst produces a diversity of landforms and alters the physical environment in dynamic ways. To estimate potential changes to the carbon cycle it is imperative to quantify the size and distribution of thermokarst landforms. By performing a supervised classification on a high resolution IKONOS image, we detected and mapped small, irregular thermokarst features occurring within an upland watershed in discontinuous permafrost of Interior Alaska. We found that 12% of the Eight Mile Lake (EML) watershed has undergone thermokarst, predominantly in valleys where tussock tundra resides. About 35% of the 3.7 km2 tussock tundra class has likely transitioned to thermokarst. These landscape level changes created by permafrost thaw at EML have important implications for ecosystem carbon cycling because thermokarst features are forming in carbon-rich areas and are altering the hydrology in ways that increase seasonal thawing of the soil.

Belshe, E. F.; Schuur, E. A. G.; Grosse, G.

2013-09-01

41

High resolution cloud feature tracking on Venus by Galileo  

NASA Technical Reports Server (NTRS)

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.

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

1994-01-01

42

Branching and circular features in high dimensional data.  

PubMed

Large observations and simulations in scientific research give rise to high-dimensional data sets that present many challenges and opportunities in data analysis and visualization. Researchers in application domains such as engineering, computational biology, climate study, imaging and motion capture are faced with the problem of how to discover compact representations of high-dimensional data while preserving their intrinsic structure. In many applications, the original data is projected onto low-dimensional space via dimensionality reduction techniques prior to modeling. One problem with this approach is that the projection step in the process can fail to preserve structure in the data that is only apparent in high dimensions. Conversely, such techniques may create structural illusions in the projection, implying structure not present in the original high-dimensional data. Our solution is to utilize topological techniques to recover important structures in high-dimensional data that contains non-trivial topology. Specifically, we are interested in high-dimensional branching structures. We construct local circle-valued coordinate functions to represent such features. Subsequently, we perform dimensionality reduction on the data while ensuring such structures are visually preserved. Additionally, we study the effects of global circular structures on visualizations. Our results reveal never-before-seen structures on real-world data sets from a variety of applications. PMID:22034307

Wang, Bei; Summa, Brian; Pascucci, Valerio; Vejdemo-Johansson, Mikael

2011-12-01

43

Efficient learning and feature selection in high-dimensional regression.  

PubMed

We present a novel algorithm for efficient learning and feature selection in high-dimensional regression problems. We arrive at this model through a modification of the standard regression model, enabling us to derive a probabilistic version of the well-known statistical regression technique of backfitting. Using the expectation-maximization algorithm, along with variational approximation methods to overcome intractability, we extend our algorithm to include automatic relevance detection of the input features. This variational Bayesian least squares (VBLS) approach retains its simplicity as a linear model, but offers a novel statistically robust black-box approach to generalized linear regression with high-dimensional inputs. It can be easily extended to nonlinear regression and classification problems. In particular, we derive the framework of sparse Bayesian learning, the relevance vector machine, with VBLS at its core, offering significant computational and robustness advantages for this class of methods. The iterative nature of VBLS makes it most suitable for real-time incremental learning, which is crucial especially in the application domain of robotics, brain-machine interfaces, and neural prosthetics, where real-time learning of models for control is needed. We evaluate our algorithm on synthetic and neurophysiological data sets, as well as on standard regression and classification benchmark data sets, comparing it with other competitive statistical approaches and demonstrating its suitability as a drop-in replacement for other generalized linear regression techniques. PMID:20028222

Ting, Jo-Anne; D'Souza, Aaron; Vijayakumar, Sethu; Schaal, Stefan

2010-04-01

44

ATM controls proper mitotic spindle structure.  

PubMed

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

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

2014-04-01

45

Centromeric Barrier Disruption Leads to Mitotic Defects in Schizosaccharomyces pombe  

PubMed Central

Centromeres are cis-acting chromosomal domains that direct kinetochore formation, enabling faithful chromosome segregation and preserving genome stability. The centromeres of most eukaryotic organisms are structurally complex, composed of nonoverlapping, structurally and functionally distinct chromatin subdomains, including the specialized core chromatin that underlies the kinetochore and pericentromeric heterochromatin. The genomic and epigenetic features that specify and preserve the adjacent chromatin subdomains critical to centromere identity are currently unknown. Here we demonstrate that chromatin barriers regulate this process in Schizosaccharomyces pombe. Reduced fitness and mitotic chromosome segregation defects occur in strains that carry exogenous DNA inserted at centromere 1 chromatin barriers. Abnormal phenotypes are accompanied by changes in the structural integrity of both the centromeric core chromatin domain, containing the conserved CENP-ACnp1 protein, and the flanking pericentric heterochromatin domain. Barrier mutant cells can revert to wild-type growth and centromere structure at a high frequency after the spontaneous excision of integrated exogenous DNA. Our results reveal a previously undemonstrated role for chromatin barriers in chromosome segregation and in the prevention of genome instability. PMID:24531725

Gaither, Terilyn L.; Merrett, Stephanie L.; Pun, Matthew J.; Scott, Kristin C.

2014-01-01

46

Mitotic Waves in Laticifers of Euphorbia marginata.  

PubMed

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

Mahlberg, P; Sabharwal, P

1966-04-22

47

Highly Nonrandom Features of Synaptic Connectivity in Local Cortical Circuits  

PubMed Central

How different is local cortical circuitry from a random network? To answer this question, we probed synaptic connections with several hundred simultaneous quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual cortex. Analysis of this dataset revealed several nonrandom features in synaptic connectivity. We confirmed previous reports that bidirectional connections are more common than expected in a random network. We found that several highly clustered three-neuron connectivity patterns are overrepresented, suggesting that connections tend to cluster together. We also analyzed synaptic connection strength as defined by the peak excitatory postsynaptic potential amplitude. We found that the distribution of synaptic connection strength differs significantly from the Poisson distribution and can be fitted by a lognormal distribution. Such a distribution has a heavier tail and implies that synaptic weight is concentrated among few synaptic connections. In addition, the strengths of synaptic connections sharing pre- or postsynaptic neurons are correlated, implying that strong connections are even more clustered than the weak ones. Therefore, the local cortical network structure can be viewed as a skeleton of stronger connections in a sea of weaker ones. Such a skeleton is likely to play an important role in network dynamics and should be investigated further. PMID:15737062

2005-01-01

48

Unusual features of the high light acclimation of Chromera velia.  

PubMed

In the present study, the high light (HL) acclimation of Chromera velia (Chromerida) was studied. HL-grown cells exhibited an increased cell volume and dry weight compared to cells grown at medium light (ML). The chlorophyll (Chl) a-specific absorption spectra ([Formula: see text]) of the HL cells showed an increased absorption efficiency over a wavelength range from 400 to 750 nm, possibly due to differences in the packaging of Chl a molecules. In HL cells, the size of the violaxanthin (V) cycle pigment pool was strongly increased. Despite a higher concentration of de-epoxidized V cycle pigments, non-photochemical quenching (NPQ) of the HL cells was slightly reduced compared to ML cells. The analysis of NPQ recovery during low light (LL) after a short illumination with excess light showed a fast NPQ relaxation and zeaxanthin epoxidation. Purification of the pigment-protein complexes demonstrated that the HL-synthesized V was associated with the chromera light-harvesting complex (CLH). However, the difference absorption spectrum of HL minus ML CLH, together with the 77 K fluorescence excitation spectra, suggested that the additional V was not protein bound but localized in a lipid phase associated with the CLH. The polypeptide analysis of the pigment-protein complexes showed that one out of three known LHCr proteins was associated in higher concentration with photosystem I in the HL cells, whereas in ML cells, it was enriched in the CLH fraction. In conclusion, the acclimation of C. velia to HL illumination shows features that are comparable to those of diatoms, while other characteristics more closely resemble those of higher plants and green algae. PMID:24906888

Mann, Marcus; Hoppenz, Paul; Jakob, Torsten; Weisheit, Wolfram; Mittag, Maria; Wilhelm, Christian; Goss, Reimund

2014-11-01

49

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

SciTech Connect

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

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

2007-01-01

50

Mitotic cytosol inhibits invagination of coated pits in broken mitotic cells  

PubMed Central

Receptor-mediated endocytosis is inhibited during mitosis in mammalian cells and earlier work on A431 cells suggested that one of the sites inhibited was the invagination of coated pits (Pypaert, M., J. M. Lucocq, and G. Warren. 1987. Eur. J. Cell Biol. 45: 23-29). To explore this inhibition further, we have reproduced it in broken HeLa cells. Mitotic or interphase cells were broken by freeze-thawing in liquid nitrogen and warmed in the presence of mitotic or interphase cytosol. Using a morphological assay, we found invagination to be inhibited only when mitotic cells were incubated in mitotic cytosol. This inhibition was reversed by diluting the cytosol during the incubation. Reversal was sensitive to okadaic acid, a potent phosphatase inhibitor, showing that phosphorylation was involved in the inhibition of invagination. This was confirmed using purified cdc2 kinase which alone could partially substitute for mitotic cytosol. PMID:1910051

1991-01-01

51

Micromechanical study of mitotic chromosome structure  

NASA Astrophysics Data System (ADS)

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

Marko, John

2011-03-01

52

New Mitotic Regulators Released from Chromatin  

PubMed Central

Faithful action of the mitotic spindle segregates duplicated chromosomes into daughter cells. Perturbations of this process result in chromosome mis-segregation, leading to chromosomal instability and cancer development. Chromosomes are not simply passengers segregated by spindle microtubules but rather play a major active role in spindle assembly. The GTP bound form of the Ran GTPase (RanGTP), produced around chromosomes, locally activates spindle assembly factors. Recent studies have uncovered that chromosomes organize mitosis beyond spindle formation. They distinctly regulate other mitotic events, such as spindle maintenance in anaphase, which is essential for chromosome segregation. Furthermore, the direct function of chromosomes is not only to produce RanGTP but, in addition, to release key mitotic regulators from chromatin. Chromatin-remodeling factors and nuclear pore complex proteins, which have established functions on chromatin in interphase, dissociate from mitotic chromatin and function in spindle assembly or maintenance. Thus, chromosomes actively organize their own segregation using chromatin-releasing mitotic regulators as well as RanGTP. PMID:24380075

Yokoyama, Hideki; Gruss, Oliver J.

2013-01-01

53

A mitotic recombination system for mouse chromosome 17  

PubMed Central

Mitotic recombination between homologous chromosomes is a genetic technique for mosaic analysis in model organisms. The general application of this technique in the mouse depends on establishment of effective recombination systems for individual chromosomes and reliable and sensitive methods for detection of recombination events. Here, we established a Cre/LoxP-mediated recombination system in mice for mosaic analysis of full-length chromosome 17. Cre-mediated germ-line recombination between the homologous chromosomes was observed with ?9% frequency in a progeny test. Mitotic recombination in somatic tissues was evaluated and scored in B and T lymphocytes with the aid of surface markers and fluorescent-activated cell sorting. We show that a lineage-specific Cre can induce mitotic recombination with a highly reproducible frequency of 0.5–1.0% in lymphoid progenitors. The recombination system established here allows for a simple and accurate detection and isolation of recombination events in live cells, making this system particularly attractive for mosaic analysis or mutagenesis studies in the immune system. PMID:18326030

Sun, Lei; Wu, Xiaohui; Han, Min; Xu, Tian; Zhuang, Yuan

2008-01-01

54

The STARD9/Kif16a Kinesin Associates With Mitotic Microtubules and Regulates Spindle Pole Assembly  

PubMed Central

SUMMARY During cell division cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule co-purifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential anti-mitotic target. PMID:22153075

Torres, Jorge Z.; Summers, Matthew K.; Peterson, David; Brauer, Matthew J.; Lee, James; Senese, Silvia; Gholkar, Ankur A.; Lo, Yu-Chen; Lei, Xingye; Jung, Kenneth; Anderson, David C.; Davis, David P.; Belmont, Lisa; Jackson, Peter K.

2011-01-01

55

Fluorescent in situ Hybridization on Mitotic Chromosomes of Mosquitoes  

PubMed Central

Fluorescent in situ hybridization (FISH) is a technique routinely used by many laboratories to determine the chromosomal position of DNA and RNA probes. One important application of this method is the development of high-quality physical maps useful for improving the genome assemblies for various organisms. The natural banding pattern of polytene and mitotic chromosomes provides guidance for the precise ordering and orientation of the genomic supercontigs. Among the three mosquito genera, namely Anopheles, Aedes, and Culex, a well-established chromosome-based mapping technique has been developed only for Anopheles, whose members possess readable polytene chromosomes 1. As a result of genome mapping efforts, 88% of the An. gambiae genome has been placed to precise chromosome positions 2,3 . Two other mosquito genera, Aedes and Culex, have poorly polytenized chromosomes because of significant overrepresentation of transposable elements in their genomes 4, 5, 6. Only 31 and 9% of the genomic supercontings have been assigned without order or orientation to chromosomes of Ae. aegypti 7 and Cx. quinquefasciatus 8, respectively. Mitotic chromosome preparation for these two species had previously been limited to brain ganglia and cell lines. However, chromosome slides prepared from the brain ganglia of mosquitoes usually contain low numbers of metaphase plates 9. Also, although a FISH technique has been developed for mitotic chromosomes from a cell line of Ae. aegypti 10, the accumulation of multiple chromosomal rearrangements in cell line chromosomes 11 makes them useless for genome mapping. Here we describe a simple, robust technique for obtaining high-quality mitotic chromosome preparations from imaginal discs (IDs) of 4th instar larvae which can be used for all three genera of mosquitoes. A standard FISH protocol 12 is optimized for using BAC clones of genomic DNA as a probe on mitotic chromosomes of Ae. aegypti and Cx. quinquefasciatus, and for utilizing an intergenic spacer (IGS) region of ribosomal DNA (rDNA) as a probe on An. gambiae chromosomes. In addition to physical mapping, the developed technique can be applied to population cytogenetics and chromosome taxonomy/systematics of mosquitoes and other insect groups. PMID:23007640

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

2012-01-01

56

High-speed, sub-15 nm feature size thermochemical nanolithography.  

PubMed

We report a nanolithography technique that allows simultaneous direct control of the local chemistry and topography of thin polymer films. Specifically, a heated atomic force microscope (AFM) tip can write sub-15 nm hydrophilic features onto a hydrophobic polymer at the rate of 1.4 mm per s. The thermally activated chemical reactions and topography changes depend on the chemical composition of the polymer, the raster speed, the temperature at the AFM tip/sample interface, and the normal load. This method is conceptually simple, direct, extremely rapid, achievable in a range of environments, and potentially adaptable to other materials systems. PMID:17385937

Szoszkiewicz, Robert; Okada, Takashi; Jones, Simon C; Li, Tai-De; King, William P; Marder, Seth R; Riedo, Elisa

2007-04-01

57

Increased mitotic and proliferative activity are associated with worse prognosis in papillary tumors of the pineal region.  

PubMed

Papillary tumors of the pineal region are rare glial tumors located in the vicinity of the third ventricle, the clinical behavior of which is often aggressive. Little is known about the prognostic markers that might aid to identify patients at increased risk for recurrence. Therefore, the prognostic value of histopathologic and clinical features was examined in a series of 21 patients. Median age of the 12 male and 9 female patients was 35 years (range, 10 to 56 y). On histopathologic examination, all tumors were characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. In addition, tumors showed increased cellularity (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis (n=8; 38%), increased mitotic activity (?3 mitoses per 10 high-power fields [n=10; 48%]), and increased proliferation (Ki67/MIB1 index ?10% [n=8/20; 40%]). Gross total resection could be achieved in 13/21 patients (62%). Postoperatively, 13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence-free survival was 66 months in 19 patients, for whom detailed follow-up information was available. Twelve patients (63%) experienced tumor progression. Three patients (16%) died of disease. Among the clinical and histopathologic features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to 70] mo [median [95% confidence interval

Heim, Stephanie; Beschorner, Rudi; Mittelbronn, Michel; Keyvani, Kathy; Riemenschneider, Markus J; Vajtai, Istvan; Hartmann, Christian; Acker, Till; Blümcke, Ingmar; Paulus, Werner; Hasselblatt, Martin

2014-01-01

58

High-speed, sub-15 nm feature size thermochemical nanolithography  

NASA Astrophysics Data System (ADS)

The past decade has witnessed an explosion of techniques used to pattern materials on the nano and submicrometer scale, driven by a diversity of applications, such as molecular electronics, data storage, optoelectronics, displays, and all forms of sensors. However, there are many challenges to conventional techniques as they are approaching their fundamental size limit. Here we report a nanolithography technique that allows simultaneous direct control of the local chemistry and topography of thin polymer films. Specifically, a heated atomic force microscope tip can write sub-15 nanometer hydrophilic features over a hydrophobic polymer at the rate of 1.4 millimeters per second. This method is simple, direct, extremely rapid, achievable in a range of environments, and easily adaptable to other materials systems.

Riedo, Elisa; Szoszkiewicz, Robert; Okada, Takashi; Jones, Simon; Li, Tai-De; King, William; Marder, Seth

2007-03-01

59

Architectural Design Features of a Programmable High Throughput AES Coprocessor  

E-print Network

with domain specific instructions for Gbit throughput IPSec and other applications. Our design is a loosely in a large number of applications. High-speed IPSec applications like VPN and Giga-bit Ethernet are examples of such applications that require high performance and flexible security engines. VPN applications that use IPSec

Schaumont, Patrick

60

Rapid measurement of mitotic spindle orientation in cultured mammalian cells  

PubMed Central

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

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

2014-01-01

61

Mitotic Waves in Laticifers of Euphorbia marginata  

Microsoft Academic Search

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

Paul Mahlberg; Pritam Sabharwal

1966-01-01

62

Death through a tragedy: mitotic catastrophe  

Microsoft Academic Search

Mitotic catastrophe (MC) has long been considered as a mode of cell death that results from premature or inappropriate entry of cells into mitosis and can be caused by chemical or physical stresses. Whereas it initially was depicted as the main form of cell death induced by ionizing radiation, it is today known to be triggered also by treatment with

H Vakifahmetoglu; M Olsson; B Zhivotovsky

2008-01-01

63

Phosphoproteome analysis of the human mitotic spindle  

PubMed Central

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 has to be tightly regulated in time and space. Reversible phosphorylation has been shown to be one of the key regulatory mechanisms for the organization of the mitotic spindle. The relatively low number of identified in vivo phosphorylation sites of spindle components, however, has hampered functional analysis of regulatory spindle networks. A more complete inventory of the phosphorylation sites of spindle-associated proteins would therefore constitute an important advance. Here, we describe the mass spectrometry-based identification of in vivo phosphorylation sites from purified human mitotic spindles. In total, 736 phosphorylation sites were identified, of which 312 could be attributed to known spindle proteins. Among these are phosphorylation sites that were previously shown to be important for the regulation of spindle-associated proteins. Importantly, this data set also comprises 279 novel phosphorylation sites of known spindle proteins for future functional studies. This inventory of spindle phosphorylation sites should thus make an important contribution to a better understanding of the molecular mechanisms that regulate the formation, function, and integrity of the mitotic spindle. PMID:16565220

Nousiainen, Marjaana; Sillje, Herman H. W.; Sauer, Guido; Nigg, Erich A.; Korner, Roman

2006-01-01

64

Mitotic rate is a more reliable unfavorable prognosticator than ulceration for early cutaneous melanoma: A 5-year survival analysis.  

PubMed

The presence of ulceration has been considered as one of the most important primary tumor characteristics of cutaneous malignant melanoma (CMM) for predicting patient outcome. Yet recently, scientific attention has been drawn towards another microscopic feature of primary tumors, the mitotic rate (MR). The present study aimed to examine the relationship between the presence of ulceration and the mitotic rate and clinicopathological characteristics and melanoma patient survival, and to discuss the results in the context of AJCC melanoma staging recommendations. Tissue samples were obtained from 104 patients treated for CMM. In classical H&E staining, the mitotic rate and the presence of ulceration were evaluated. Non-mitogenic tumors were defined as having 0 mitoses/mm2, low mitogenic potential, 1-2 mitoses/mm2 and highly mitogenic tumors, ?3 mitoses/mm2. In the entire group of 104 patients, a high mitotic rate (hMR) and ulceration were highly negative prognostic factors, and indicated considerably shorter overall survival, cancer-specific overall survival and disease-free survival. Notably, hMR appeared to have a statistically significant negative impact on survival in early melanomas in both the pT1 (P=0.001) and pT2 subgroups (P=0.006). Kaplan?Meier analysis of the remaining subsets (pT3 and pT4) did not reveal any important differences in the 5-year survival with regard to MR values. The presence of ulceration also had a prognostic significance for early melanomas, but only for pT1 tumors (P=0.05). Multivariate analysis confirmed that hMR was strongly associated with an unfavorable prognosis. Ulceration had no prognostic significance in the Cox proportional hazards model. Considering the biology of melanoma, hMR seems to be a more reliable parameter than the presence of ulceration. The value of MR categorizes melanomas into tumors with low or high proliferative potential, thus giving direct information concerning their capacity to infiltrate deeper layers of the dermis and, potentially, to generate regional lymph node and distant metastases. PMID:25310673

Donizy, Piotr; Kaczorowski, Maciej; Leskiewicz, Marek; Zietek, Marcin; Pieniazek, Malgorzata; Kozyra, Cyprian; Halon, Agnieszka; Matkowski, Rafal

2014-12-01

65

STEM High School Communities: Common and Differing Features  

ERIC Educational Resources Information Center

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

Tofel-Grehl, Colby; Callahan, Carolyn M.

2014-01-01

66

High resolution 3D “snapshot” ISAR imaging and feature extraction  

Microsoft Academic Search

We have developed a new formulation for three dimensional (3D) radar imaging of inverse synthetic aperture radar (ISAR) data based on recent developments in high resolution spectral estimation theory. Typically for non real-time applications, image formation is a two step process consisting of motion determination and image generation. The technique presented focuses on this latter process, and assumes the motion

J. T. Mayhan; M. L. Burrows; K. M. Cuomo; J. E. Piou

2001-01-01

67

Some Features of Magnetic Storms in High Latitudes  

Microsoft Academic Search

During a severe magnetic storm, observatory records obtained in high latitudes may show a type of disturbance here called a 'cusped bay,' characterized by a marked displacement of the trace, coupled with augmented short-period fluctuations. Several of these events registered during the IGY at stations near the northern and southern auroral zones, some with amplitudes approaching 2000 ?, were measured

David G. Knapp

1961-01-01

68

Unusual features in high statistics radar meteor studies at EISCAT  

NASA Astrophysics Data System (ADS)

We describe results of an experiment conducted with the European Incoherent Scatter (EISCAT) radars during three 8-h runs on consecutive nights in 2008 December aiming to detect and study the high-altitude meteor population along with the meteors detected at classical ~100-km altitudes. The experiment used coaxial ultra-high-frequency (UHF) and very high-frequency (VHF) radar beams pointed vertically to the zenith of Ramfjordmoen near Tromsø (Norway), and remote UHF receivers at Kiruna (Sweden) and Sodankylä (Finland) for tristatic observations of a very limited volume at an altitude of 170 km above the transmitter site. The EISCAT VHF radar detected during the 24-h period 22698 echoes identified as meteors. The number of UHF echoes in the same period was 2138, most detected also at VHF. Among the VHF meteors, 11 were detected at altitudes higher than 150 km. Of these, the record highest meteor was at 246.9 km. No high-altitude UHF echoes were detected, none was tristatic, and no echoes with a Doppler velocity above ~60 km s-1 were identified. Given the large number of echoes, which argues in favour of a highly significant characterization of the meteoroid population, we discuss the statistical properties of the detections and their possible physical nature. The average detection rate of VHF radar meteors was about 16 min-1. Comparing this high rate with that of the faintest optically detected meteors indicates that the radar detections originate from a meteoroid population that could be as optically faint as 13-14 mag. We did not observe a marked enhancement of the rates at the peak of the Geminid shower, confirming once again the proposal that most faint meteors, be these radar or optical, belong to the sporadic population and not to a specific shower. For a few meteors, our data show definite deceleration and possible fragmentation. A simple calculation indicates that one of the detected meteoroids was a submillimetre body that fragmented when the ram pressure reached about 0.5 pascal. This is much lower than the pressure that fragments brighter cometary meteors, which is at least two orders of magnitude higher.

Brosch, Noah; Häggström, Ingemar; Pellinen-Wannberg, Asta; Westman, Assar

2010-01-01

69

Prolonged oestrogen treatment does not correlate with a sustained increase in anterior pituitary mitotic index in ovariectomized Wistar rats  

PubMed Central

Oestrogen is a powerful mitogen that is believed to exert a continuous, dose-dependent trophic stimulus at the anterior pituitary. This persistent mitotic effect contrasts with corticosterone and testosterone, changes in the levels of which induce only transient, self-limiting fluctuations in pituitary mitotic activity. To further define the putative long-term trophic effects of oestrogen, we have accurately analysed the effects of 7 and 28 days oestrogen treatment on anterior pituitary mitotic activity in ovariectomized 10-week-old Wistar rats using both bromodeoxyuridine (BrdU) and timed colchicine-induced mitotic arrest. An oestrogen dose-dependent increase in mitotic index was seen 7 days after the start of treatment as expected, representing an acceleration in gross mitotic activity from 1·7%/day in ovariectomized animals in the absence of any oestrogen replacement to 3·7%/day in the presence of a pharmacological dose of oestrogen (50?mcg/rat per day: ?230?mcg/kg per day). Despite continued exposure to high-dose oestrogen and persistence of the increase in pituitary wet weight, the increase in mitotic index was unexpectedly not sustained. After 28 days of high-dose oestrogen treatment, anterior pituitary mitotic index and BrdU-labelling index were not significantly different from baseline. Although a powerful pituitary mitogen in the short term, responsible, presumably, for increased trophic variability in oestrus cycling females, these data indicate that in keeping with other trophic stimuli to the pituitary and in contrast to a much established dogma, the mitotic response to longer-term high-dose oestrogen exposure is transient and is not the driver of persistent pituitary growth, at least in female Wistar rats. PMID:19106235

Nolan, L A; Levy, A

2009-01-01

70

Radmis, a Novel Mitotic Spindle Protein that Functions in Cell Division of Neural Progenitors  

PubMed Central

Developmental dynamics of neural stem/progenitor cells (NSPCs) are crucial for embryonic and adult neurogenesis, but its regulatory factors are not fully understood. By differential subtractive screening with NSPCs versus their differentiated progenies, we identified the radmis (radial fiber and mitotic spindle)/ckap2l gene, a novel microtubule-associated protein (MAP) enriched in NSPCs. Radmis is a putative substrate for the E3-ubiquitin ligase, anaphase promoting complex/cyclosome (APC/C), and is degraded via the KEN box. Radmis was highly expressed in regions of active neurogenesis throughout life, and its distribution was dynamically regulated during NSPC division. In embryonic and perinatal brains, radmis localized to bipolar mitotic spindles and radial fibers (basal processes) of dividing NSPCs. As central nervous system development proceeded, radmis expression was lost in most brain regions, except for several neurogenic regions. In adult brain, radmis expression persisted in the mitotic spindles of both slowly-dividing stem cells and rapid amplifying progenitors. Overexpression of radmis in vitro induced hyper-stabilization of microtubules, severe defects in mitotic spindle formation, and mitotic arrest. In vivo gain-of-function using in utero electroporation revealed that radmis directed a reduction in NSPC proliferation and a concomitant increase in cell cycle exit, causing a reduction in the Tbr2-positive basal progenitor population and shrinkage of the embryonic subventricular zone. Besides, radmis loss-of-function by shRNAs induced the multipolar mitotic spindle structure, accompanied with the catastrophe of chromosome segregation including the long chromosome bridge between two separating daughter nuclei. These findings uncover the indispensable role of radmis in mitotic spindle formation and cell-cycle progression of NSPCs. PMID:24260314

Yumoto, Takahito; Nakadate, Kazuhiko; Nakamura, Yuki; Sugitani, Yoshinobu; Sugitani-Yoshida, Reiko; Ueda, Shuichi; Sakakibara, Shin-ichi

2013-01-01

71

Techniques for Automated Extraction of Roadway Inventory Features from High?Resolution Satellite Imagery  

Microsoft Academic Search

The emergence of high?resolution satellite imagery is attracting new applications which can take advantage of remotely sensed data for mapping, inventory, and change detection. Automated collection of roadway inventory features is one such application. To this end, it is important to investigate the performance of conventional feature extraction techniques when applied to high?resolution images and to develop new techniques for

Hassan A. Karimi; Xiaolong Dai; Siamak Khorram; Aemal J. Khattak; Joseph E. Hummer

1999-01-01

72

Mitotic DNA damages induced by carbon-ion radiation incur additional chromosomal breaks in polyploidy.  

PubMed

Compared with low linear energy transfer (LET) radiation, carbon-ion radiation has been proved to induce high frequency of more complex DNA damages, including DNA double strands (DSBs) and non-DSB clustered DNA lesions. Chemotherapeutic drug doxorubicin has been reported to elicit additional H2AX phosphorylation in polyploidy. Here, we investigated whether mitotic DNA damage induced by high-LET carbon-ion radiation could play the same role. We demonstrate that impairment of post-mitotic G1 and S arrest and abrogation of post-mitotic G2-M checkpoint failed to prevent mis-replication of damaged DNA and mis-separation of chromosomes. Meanwhile, mitotic slippage only nocodazole-related, cytokinesis failure and cell fusion collectively contributed to the formation of binucleated cells. Chk1 and Cdh1 activation was inhibited when polyploidy emerged in force, both of which are critical components for mitotic exit and cytokinesis. Carbon-ion radiation irrelevant of nocodazole incurred additional DNA breaks in polyploidy, manifesting as structural and numerical karyotype changes. The proliferation of cells given pre-synchronization and radiation was completely inhibited and cells were intensely apoptotic. Since increased chromosomal damage resulted in extensive H2AX phosphorylation during polyploidy, we propose that the additional ?-H2AX during polyploidy incurred by carbon-ion radiation provides a final opportunity for these dangerous and chromosomally unstable cells to be eliminated. PMID:25123929

Li, Ping; Zhou, Libin; Liu, Xiongxiong; Jin, Xiaodong; Zhao, Ting; Ye, Fei; Liu, Xinguo; Hirayama, Ryoichi; Li, Qiang

2014-10-01

73

Automatic microscopy for mitotic cell location.  

NASA Technical Reports Server (NTRS)

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.

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

1972-01-01

74

Two Mammalian Mitotic Aurora Kinases: Who's Who?  

NSDL National Science Digital Library

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.

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

2001-03-13

75

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

PubMed Central

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

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

2014-01-01

76

Structure of the mitotic checkpoint complex.  

PubMed

In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome segregation. Here, using the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20), we reveal the molecular basis of MCC-mediated APC/C inhibition and the regulation of MCC assembly. The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. Mad3 and p31(comet) (also known as MAD2L1-binding protein) compete for the same C-Mad2 interface, which explains how p31(comet) disrupts MCC assembly to antagonize the SAC. This study shows how APC/C inhibition is coupled to degron recognition by co-activators. PMID:22437499

Chao, William C H; Kulkarni, Kiran; Zhang, Ziguo; Kong, Eric H; Barford, David

2012-04-12

77

Feature Selection in Highly Redundant Signal Data: A Case Study in Vehicle Telemetry Data  

E-print Network

Feature Selection in Highly Redundant Signal Data: A Case Study in Vehicle Telemetry Data such as vehicle telemetry, medical sensors, or financial time-series, and it is possible for feature redundancies illustrate the process on vehicle telemetry signal data collected in a driver distraction monitoring project

Griffiths, Nathan

78

Opening the Black Box of Feature Extraction: Incorporating Visualization into High-Dimensional Data Mining Processes  

Microsoft Academic Search

Feature extraction techniques have been used to handle high-dimensional data and experimental studies often show improved classification accuracies. Unfortunately very few studies provide concrete evidences on the effectiveness of these feature extraction techniques and they largely remain to be black boxes. In this study, we design and implement a visualization prototype system that allows users to look into the classification

Jianting Zhang; Le Gruenwald

2006-01-01

79

Classification of High-Resolution NMR Spectra Based on Complex Wavelet Domain Feature Selection and Kernel-  

E-print Network

Classification of High-Resolution NMR Spectra Based on Complex Wavelet Domain Feature Selection spectra based on the selected features. Our experiments with real NMR spectra showed that the proposed signal. In [6], decimated discrete wavelet transform was employed to analyze mass spectrometry data

Wang, Zhou

80

Mitotic disturbance associated with mosaic aneuploidies  

Microsoft Academic Search

The association of various unsystematic aneuploidies with premature centromere division (PCD) was observed in a patient with conspicuous clinical features and combined immunodeficiency. Trisomies and monosomies of almost all autosomes and gonosomal aberrations were found separately or in combination in a majority of the proband's lymphocytes and fibroblasts. The chromosome number varied from 44 to 50. A high proportion of

K. Miller; W. Miiller; L. Winkler; M. R. Hadam; J. H. H. Ehrich; Sibylle D. Flatz

1990-01-01

81

Mitotic Recombination in Yeast: Isolation and Characterization of Mutants with Enhanced Spontaneous Mitotic Gene Conversion Rates  

PubMed Central

Semi-dominant mutants displaying greatly elevated (up to 200-fold above control) 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 recombination, 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. PMID:7002715

Maloney, Daniel H.; Fogel, Seymour

1980-01-01

82

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

PubMed Central

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

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

2013-01-01

83

Function and regulation of dynein in mitotic chromosome segregation.  

PubMed

Cytoplasmic dynein is a large minus-end-directed microtubule motor complex, involved in many different cellular processes including intracellular trafficking, organelle positioning, and microtubule organization. Furthermore, dynein plays essential roles during cell division where it is implicated in multiple processes including centrosome separation, chromosome movements, spindle organization, spindle positioning, and mitotic checkpoint silencing. How is a single motor able to fulfill this large array of functions and how are these activities temporally and spatially regulated? The answer lies in the unique composition of the dynein motor and in the interactions it makes with multiple regulatory proteins that define the time and place where dynein becomes active. Here, we will focus on the different mitotic processes that dynein is involved in, and how its regulatory proteins act to support dynein. Although dynein is highly conserved amongst eukaryotes (with the exception of plants), there is significant variability in the cellular processes that depend on dynein in different species. In this review, we concentrate on the functions of cytoplasmic dynein in mammals but will also refer to data obtained in other model organisms that have contributed to our understanding of dynein function in higher eukaryotes. PMID:24871939

Raaijmakers, J A; Medema, R H

2014-10-01

84

Revertant somatic mosaicism by mitotic recombination in dyskeratosis congenita.  

PubMed

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

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

85

Symplekin Specifies Mitotic Fidelity by Supporting Microtubule Dynamics ? †  

PubMed Central

Using a pangenomic loss-of-function screening strategy, we have previously identified 76 potent modulators of paclitaxel responsiveness in non-small-cell lung cancer. The top hit isolated from this screen, symplekin, is a well-established component of the mRNA polyadenylation machinery. Here, we performed a high-resolution phenotypic analysis to reveal the mechanistic underpinnings by which symplekin depletion collaborates with paclitaxel. We find that symplekin supports faithful mitosis by contributing to the formation of a bipolar spindle apparatus. Depletion of symplekin attenuates microtubule polymerization activity as well as expression of the critical microtubule polymerization protein CKAP5 (TOGp). Depletion of additional members of the polyadenylation complex induces similar phenotypes, suggesting that polyadenylation machinery is intimately coupled to microtubule function and thus mitotic spindle formation. Importantly, tumor cells depleted of symplekin display reduced fecundity, but the mitotic defects that we observe are not evident in immortalized cells. These results demonstrate a critical connection between the polyadenylation machinery and mitosis and suggest that tumor cells have an enhanced dependency on these components for spindle assembly. PMID:20823274

Cappell, Kathryn M.; Larson, Brittany; Sciaky, Noah; Whitehurst, Angelique W.

2010-01-01

86

Mitotic Phosphorylation of Histone H3: Spatio-Temporal Regulation by Mammalian Aurora Kinases  

Microsoft Academic Search

Phosphorylation at a highly conserved serine residue (Ser-10) in the histone H3 tail is considered to be a crucial event for the onset of mitosis. This modification appears early in the G2 phase within pericentromeric heterochromatin and spreads in an ordered fashion coincident with mitotic chromosome condensation. Mu- tation of Ser-10 is essential in Tetrahymena, since it results in abnormal

Claudia Crosio; Gian Maria Fimia; Romain Loury; Masashi Kimura; Yukio Okano; Hongyi Zhou; Subrata Sen; C. David Allis; Paolo Sassone-Corsi

2002-01-01

87

Construction of a mitotic linkage map of Fusarium oxysporum based on Foxy -AFLPs  

Microsoft Academic Search

Construction of the first mitotic linkage map of the asexual fungus Fusarium oxysporum, based on a population of 32 parasexual fusion products, is reported. Molecular markers were developed using a modified AFLP technique which combines a Foxy -specific primer with standard adapter primers. The retroposon Foxy is abundantly present and highly variable in location in F. oxysporum isolates: 43% of

H. A. S. Teunissen; M. Rep; P. M. Houterman; B. J. C. Cornelissen; M. A. Haring

2003-01-01

88

Miniaturization of mitotic index cell-based assay using "wall-less" plate technology.  

PubMed

The use of microscopic imaging for the accurate assessment of cells in mitosis is hampered by the round morphology of mitotic cells, which renders them poorly adherent and highly susceptible to loss during the washing stage of cell-based assays. Here, to circumvent these limitations, we make use of DropArray, a recent technology that allows high retention of weakly adherent cells and suspension cells. DropArray offers the competitive advantage of maintaining the classic high throughput format of microtiter plates while reducing classic microwell volume by up to 90% by using a drop format. Here, we present a mitotic index cell-based assay using the mitosis marker phospho histone H3 at serine 10 on a DropArray 384-well plate format. Dose-response curve analysis of the mitotic index assay with an antimitotic drug (docetaxel) on DropArray is presented that shows an effective dosage compared to previous established results similar to those obtained with conventional microtiter plates. The mitotic index assay with DropArray showed a Z-factor >0.6. Our results validate DropArray as a suitable platform for high throughput screening for compounds affecting mitosis or the cell cycle. PMID:24611478

Le Guezennec, Xavier; Phong, Mark; Nor, Liyana; Kim, Namyong

2014-03-01

89

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

PubMed

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

Zhu, Yanting; Zhou, Yuan; Shi, Jue

2014-06-01

90

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

PubMed Central

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

Sun, Yijun; Todorovic, Sinisa; Goodison, Steve

2012-01-01

91

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

PubMed Central

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

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

92

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

PubMed

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

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

2007-01-01

93

Cytoplasmic dynein plays a role in mammalian mitotic spindle formation  

Microsoft Academic Search

The formation and functioning of a mitotic spindle depends not only on the assembly\\/disassembly of microtubules but also on the action of motor en- zymes. Cytoplasmic dynein has been localized to spindles, but whether or how it functions in mitotic processes is not yet known. We have cloned and ex- pressed DNA fragments that encode the putative ATP- hydrolytic sites

Eugeni A. Vaisberg; Michael P. Koonce; J. R. Mclntosh

1993-01-01

94

Mitotic Spindle Motors J. M. Scholey and A. Mogilner  

E-print Network

14 Mitotic Spindle Motors J. M. Scholey and A. Mogilner 14.1 Microtubules, Motors and Mitosis Mitosis, the process by which identical copies of the replicated genome are distrib- uted to the daughter of chromosomes and the positioning of spindle poles throughout mitosis depend upon mitotic motors, proteins

Mogilner, Alex

95

The Mitotic Spindle: A Self-Made Machine  

NSDL National Science Digital Library

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.

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

2001-10-19

96

A new role for Rab GTPases during early mitotic stages.  

PubMed

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

Das, Sanchaita; Hehnly, Heidi; Doxsey, Stephen

2014-06-12

97

Random mitotic activities across human embryonic stem cell colonies.  

SciTech Connect

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.

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

2010-08-01

98

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

PubMed Central

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

Xia, Wei; Yin, Shouyi; Ouyang, Peng

2013-01-01

99

Minimax sparse logistic regression for very high-dimensional feature selection.  

PubMed

Because of the strong convexity and probabilistic underpinnings, logistic regression (LR) is widely used in many real-world applications. However, in many problems, such as bioinformatics, choosing a small subset of features with the most discriminative power are desirable for interpreting the prediction model, robust predictions or deeper analysis. To achieve a sparse solution with respect to input features, many sparse LR models are proposed. However, it is still challenging for them to efficiently obtain unbiased sparse solutions to very high-dimensional problems (e.g., identifying the most discriminative subset from millions of features). In this paper, we propose a new minimax sparse LR model for very high-dimensional feature selections, which can be efficiently solved by a cutting plane algorithm. To solve the resultant nonsmooth minimax subproblems, a smoothing coordinate descent method is presented. Numerical issues and convergence rate of this method are carefully studied. Experimental results on several synthetic and real-world datasets show that the proposed method can obtain better prediction accuracy with the same number of selected features and has better or competitive scalability on very high-dimensional problems compared with the baseline methods, including the l1-regularized LR. PMID:24808598

Tan, Mingkui; Tsang, Ivor W; Wang, Li

2013-10-01

100

Force and Length in the Mitotic Spindle  

PubMed Central

The mitotic spindle assembles to a steady-state length at metaphase through the integrated action of molecular mechanisms that generate and respond to mechanical forces. While molecular mechanisms that produce force have been described, our understanding of how they integrate with each other, and with the assembly-disassembly mechanisms that regulate length, is poor. We review current understanding of the basic architecture and dynamics of the metaphase spindle, and some of the elementary force producing mechanisms. We then discuss models for force integration, and spindle length determination. We also emphasize key missing data that notably includes absolute values of forces, and how they vary as a function of position, within the spindle. PMID:19906577

Dumont, Sophie; Mitchison, Timothy J.

2009-01-01

101

Inherited X-chromosome inverted tandem duplication in a male traced to a grandparental mitotic error.  

PubMed Central

A male infant was referred for cytogenetic evaluation because of dysmorphic features and developmental delay. In both lymphocytes and skin fibroblasts, a modal number of 46 chromosomes was obtained with an obvious elongation of the long arm of the X chromosome (Xq+). Studies of seven members in 3 generations of this family showed that the proband's mother, sister, and maternal grandmother were phenotypically normal carriers of this abnormal X chromosome. High resolution GTG- and RBG-banding defined the extra chromatin material as an inverted duplication of Xq21----Xq24. This was supported by an approximate twofold increase in alpha-galactosidase A activity, localized to Xq21----q24, observed in the proband's lymphocytes and fibroblasts. BrdU-incorporation studies of the mother's lymphocytes showed the abnormal X to be late replicating in all 100 cells studied and normal alpha-galactosidase A levels. Cytogenetic analysis of the maternal grandmother revealed cytogenetic mosaicism with one cell line containing the abnormal X (37%), and the other, a normal female karyotype (63%). This family is instructive since: (1) it represents only the second case of a dysmorphic male demonstrating a confirmed interstitial partial Xq duplication, and (2) the origin of this familial structural rearrangement has been traced to a grandparental mitotic error. Images Fig. 1 Fig. 2 PMID:3459356

Schwartz, S; Schwartz, M F; Panny, S R; Peterson, C J; Waters, E; Cohen, M M

1986-01-01

102

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

PubMed

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

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

2014-11-15

103

Mitotic disturbance associated with mosaic aneuploidies.  

PubMed

The association of various unsystematic aneuploidies with premature centromere division (PCD) was observed in a patient with conspicuous clinical features and combined immunodeficiency. Trisomies and monosomies of almost all autosomes and gonosomal aberrations were found separately or in combination in a majority of the proband's lymphocytes and fibroblasts. The chromosome number varied from 44 to 50. A high proportion of the metaphases showed PCD or had the appearance of C-anaphases. These findings probably represent a new mutant affecting mitosis and causing mosaic aneuploidies. PMID:2307459

Miller, K; Müller, W; Winkler, L; Hadam, M R; Ehrich, J H; Flatz, S D

1990-03-01

104

Recombinogenic conditions influence partner choice in spontaneous mitotic recombination.  

PubMed

Mammalian common fragile sites are loci of frequent chromosome breakage and putative recombination hotspots. Here, we utilized Replication Slow Zones (RSZs), a budding yeast homolog of the mammalian common fragile sites, to examine recombination activities at these loci. We found that rates of URA3 inactivation of a hisG-URA3-hisG reporter at RSZ and non-RSZ loci were comparable under all conditions tested, including those that specifically promote chromosome breakage at RSZs (hydroxyurea [HU], mec1? sml1?, and high temperature), and those that suppress it (sml1? and rrm3?). These observations indicate that RSZs are not recombination hotspots and that chromosome fragility and recombination activity can be uncoupled. Results confirmed recombinogenic effects of HU, mec1? sml1?, and rrm3? and identified temperature as a regulator of mitotic recombination. We also found that these conditions altered the nature of recombination outcomes, leading to a significant increase in the frequency of URA3 inactivation via loss of heterozygosity (LOH), the type of genetic alteration involved in cancer development. Further analyses revealed that the increase was likely due to down regulation of intrachromatid and intersister (IC/IS) bias in mitotic recombination, and that RSZs exhibited greater sensitivity to HU dependent loss of IC/IS bias than non RSZ loci. These observations suggest that recombinogenic conditions contribute to genome rearrangements not only by increasing the overall recombination activity, but also by altering the nature of recombination outcomes by their effects on recombination partner choice. Similarly, fragile sites may contribute to cancer more frequently than non-fragile loci due their enhanced sensitivity to certain conditions that down-regulate the IC/IS bias rather than intrinsically higher rates of recombination. PMID:24244194

Cauwood, James D; Johnson, Anthony L; Widger, Alexander; Cha, Rita S

2013-11-01

105

A very high level of crossreactivity is an essential feature of the T-cell receptor  

Microsoft Academic Search

It is commonly accepted that a high level of antigen specificity is a feature of T-cell activation. However, here, Don Mason argues that a comprehensive response to foreign antigens requires that T cells are widely crossreactive, such that one cell reacts productively with approximately 106 different MHC-associated minimal peptide epitopes.

Don Mason

1998-01-01

106

Ultrastructural features of highly active antiretroviral therapy-associated partial lipodystrophy  

Microsoft Academic Search

Chronic treatment with highly active antiretroviral therapy (HAART) results in a novel variety of partial lipodystrophy, combining lipoatrophic and hypertrophic areas. We have previously reported the histopathological features of this disease and have also shown that adipocyte apoptosis is involved in its origin. With the aim of further elucidating the mechanisms underlying this peculiar disorder, we performed an ultrastructural study

Josep Lloreta; Pere Domingo; Ramón M. Pujol; Juan A. Arroyo; Núria Baixeras; Xavier Matias-Guiu; Montserrat Gilaberte; Maria A. Sambeat; Sergi Serrano

2002-01-01

107

Why School Based Assessment Is Not a Universal Feature of High Stakes Assessment Systems?  

ERIC Educational Resources Information Center

Accepting that school based assessment may have the potential to bring additional reliability to the assessment outcomes of an educational system, this research uses Generalizability Theory to address the question "why school based assessment is not a universal feature of high stakes assessment systems"? Three major issues are identified: (a)…

Lamprianou, Iasonas; Christie, Thomas

2009-01-01

108

Designing High Performance DSM Systems using InfiniBand Features Ranjit Noronha and Dhabaleswar K. Panda  

E-print Network

Designing High Performance DSM Systems using InfiniBand Features Ranjit Noronha and Dhabaleswar K,panda}@cis.ohio-state.edu Abstract Software DSM systems do not perform well because of the combined effects of increase DSM system. In this paper we propose a new scheme NEW- GENDSM with two components ARDMAR and DRAW

Panda, Dhabaleswar K.

109

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

E-print Network

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

Moreno-Noguer, Francesc

110

High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients with Primary Immunodeficiencies  

E-print Network

High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients, Ministry of Health, Tunis, Tunisiad To estimate the susceptibility to enterovirus infection), enteroviruses were assessed in stool specimens of 82 patients with humoral, com- bined, and other PIDs. Isolated

Paris-Sud XI, Université de

111

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

ERIC Educational Resources Information Center

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

Cid, Maria R.

2011-01-01

112

CUTLASS/IMAGE observations of high-latitude convection features during substorms  

E-print Network

ground magnetic perturbations during the sub- storm expansion phase. Localised electrojet features is discussed. 1 Introduction Substorm physics remains a very active ®eld and in spite of recent progress ground magnetic ®eld measurements. The HF radar technique is particularly useful in the high conductivity

Boyer, Edmond

113

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

E-print Network

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

Wachs, Juan

114

Tectonic Features in the Equatorial Lowlands of Mercury Viewed at High Incidence Angles  

NASA Astrophysics Data System (ADS)

The spatial distribution of tectonic features on Mercury, although not fully understood, is related to the stress regime and the mechanical properties of the lithosphere during the time that the features formed and remained active. Lobate scarps and high-relief ridges, compressional features that generally have ~1 km of relief and are hundreds of kilometers long, were identified on Mercury from images acquired during the Mariner 10 and MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) flybys. Images taken from orbit during the primary MESSENGER mission, with full coverage of the surface, confirmed that these scarps and ridges appear to be concentrated in three broad, north-south bands. Images at high incidence angles, collected since April 2012 during the MESSENGER extended mission, provide a more complete picture of the spatial extent and orientations of these features, and of their relationship to neighboring landforms. Digital elevation models, from laser altimetry and stereo imaging, additionally allow for comparisons between tectonic landforms and elevation and for measurements of slope and relief across individual features. Scarps and ridges are found at a wide range of elevations on Mercury. The greatest concentration of such features in an equatorial lowland setting is in an area (40°N-40°S, 220°-270°E) that is within one of the three north-south bands of tectonic features. Within this area, the 48 previously mapped features generally do not display preferred orientations or a consistent relationship to topography. Of these scarps, 47 were identified in flyby images and one in orbital images. Three follow the rim of Beethoven basin (10°-30°S, 225-245°E, ~600 km diameter), likely having formed along earlier zones of weakness in the crust created during formation of the basin. From recent images taken at high incidence angles, which currently have ~75% coverage in this equatorial lowland area, we are able to identify only seven additional tectonic features, all within Beethoven basin. Six of these newly identified features are also subparallel to the basin rim. However, no other scarps in our study area are so clearly connected to a particular topographic or geologic feature. The 22 lobate scarps and high-relief ridges in the northeastern quadrant of our study area have similar base elevations (average of -0.78 km, standard deviation of 0.17 km) and relief. Maximum measured relief (along one scarp) averages 0.59 km (standard deviation of 0.13 km), with a median of 0.56 km. Additionally, the scarps often terminate at a neighboring scarp, in six cases such that the two scarps are tangent to each other, and in four cases such that they intersect at an angle of ?45°. These similarities and relationships suggest that the 22 features may be tectonically linked and may have therefore formed as an assemblage within a relatively short interval of time. This assemblage of faults is located in an area of apparently limited lateral variation in crustal thickness, as indicated by crustal models consistent with long-wavelength topography and gravity. If the limited range in crustal thickness in this area was paralleled by a limited range in mechanical lithosphere thickness, this may have facilitated the formation of an assemblage of linked tectonic features.

Selvans, M. M.; Watters, T. R.; Solomon, S. C.

2012-12-01

115

Mitotic centromere-associated kinesin (MCAK): a potential cancer drug target  

PubMed Central

The inability to faithfully segregate chromosomes in mitosis results in chromosome instability, a hallmark of solid tumors. Disruption of microtubule dynamics contributes highly to mitotic chromosome instability. The kinesin-13 family is critical in the regulation of microtubule dynamics and the best characterized member of the family, the mitotic centromere-associated kinesin (MCAK), has recently been attracting enormous attention. MCAK regulates microtubule dynamics as a potent depolymerizer of microtubules by removing tubulin subunits from the polymer end. This depolymerizing activity plays pivotal roles in spindle formation, in correcting erroneous attachments of microtubule-kinetochore and in chromosome movement. Thus, the accurate regulation of MCAK is important for ensuring the faithful segregation of chromosomes in mitosis and for safeguarding chromosome stability. In this review we summarize recent data concerning the regulation of MCAK by mitotic kinases, Aurora A/B, Polo-like kinase 1 and cyclin-dependent kinase 1. We propose a molecular model of the regulation of MCAK by these mitotic kinases and relevant phosphatases throughout mitosis. An ever-increasing quantity of data indicates that MCAK is aberrantly regulated in cancer cells. This deregulation is linked to increased malignance, invasiveness, metastasis and drug resistance, most probably due to increased chromosomal instability and remodeling of the microtubule cytoskeleton in cancer cells. Most interestingly, recent observations suggest that MCAK could be a novel molecular target for cancer therapy, as a new cancer antigen or as a mitotic regulator. This collection of new data indicates that MCAK could be a new star in the cancer research sky due to its critical roles in the control of genome stability and the cytoskeleton. Further investigations are required to dissect the fine details of the regulation of MCAK throughout mitosis and its involvements in oncogenesis. PMID:22249213

Sanhaji, Mourad; Friel, Claire T.; Wordeman, Linda; Louwen, Frank; Yuan, Juping

2011-01-01

116

Plk1 Inhibition Causes Post-Mitotic DNA Damage and Senescence in a Range of Human Tumor Cell Lines  

PubMed Central

Plk1 is a checkpoint protein whose role spans all of mitosis and includes DNA repair, and is highly conserved in eukaryotes from yeast to man. Consistent with this wide array of functions for Plk1, the cellular consequences of Plk1 disruption are diverse, spanning delays in mitotic entry, mitotic spindle abnormalities, and transient mitotic arrest leading to mitotic slippage and failures in cytokinesis. In this work, we present the in vitro and in vivo consequences of Plk1 inhibition in cancer cells using potent, selective small-molecule Plk1 inhibitors and Plk1 genetic knock-down approaches. We demonstrate for the first time that cellular senescence is the predominant outcome of Plk1 inhibition in some cancer cell lines, whereas in other cancer cell lines the dominant outcome appears to be apoptosis, as has been reported in the literature. We also demonstrate strong induction of DNA double-strand breaks in all six lines examined (as assayed by ?H2AX), which occurs either during mitotic arrest or mitotic-exit, and may be linked to the downstream induction of senescence. Taken together, our findings expand the view of Plk1 inhibition, demonstrating the occurrence of a non-apoptotic outcome in some settings. Our findings are also consistent with the possibility that mitotic arrest observed as a result of Plk1 inhibition is at least partially due to the presence of unrepaired double-strand breaks in mitosis. These novel findings may lead to alternative strategies for the development of novel therapeutic agents targeting Plk1, in the selection of biomarkers, patient populations, combination partners and dosing regimens. PMID:25365521

Bowman, Doug; Shinde, Vaishali; Lasky, Kerri; Shi, Judy; Vos, Tricia; Stringer, Bradley; Amidon, Ben; D'Amore, Natalie; Hyer, Marc L.

2014-01-01

117

WAVENET feature extraction of high-range resolution radar profiles for automatic target recognition  

NASA Astrophysics Data System (ADS)

We propose a WAVENET method for feature extraction of high-range resolution (HRR) radar profiles. Because HRR signals constantly vary with incremental changes in time and target aspect, the inverse problem we address is that of extracting a subset of discriminatory features from a set of HRR profiles that are unique to each target class. Based on, we construct a neural net technique built on wavelets for determining the discriminating features separating each target class. The method involves choosing a suitable set of child wavelets, such that the transformation of the original data (the training set of HRR profiles) will enhance the nonlinear separability of different classes of target signals while significantly reducing the dimension of the data.

Morris, Hedley C.; De Pass, Monica M.

2005-03-01

118

Two-dimensional macromolecular distributions reveal detailed architectural features in high-amylose starches.  

PubMed

Two-dimensional (2D) structural distributions based on macromolecular size and branch chain-length are obtained for three maize starches with different amylose contents (one normal and two high-amylose varieties). Data were obtained using an analytical methodology combining chemical fractionation, enzymatic debranching, and offline 2D size-exclusion chromatography with multiple detection. The 2D distributions reveal novel features in the branching structure of high-amylose maize starches. Normal maize starch shows well-resolved structural topologies, corresponding to the amylopectin and amylose macromolecular populations. However, high-amylose maize starches exhibit very complex topologies with significant features between those of amylose and amylopectin, showing the presence of distinct intermediate components. These have the macromolecular size of amylose but similar branching structure to amylopectin, except for a higher proportion of longer branches. These structural features of the intermediate components can be related to a less tightly controlled biosynthesis of the branching structures in high-amylose maize starch mutants, which may prevent these molecules from maturing into full-size amylopectin. This altered macromolecular branched architecture of high-amylose starches probably contribute to their better nutritional properties. PMID:25256517

Vilaplana, Francisco; Meng, Di; Hasjim, Jovin; Gilbert, Robert G

2014-11-26

119

Discovery of metabolite features for the modelling and analysis of high-resolution NMR spectra  

PubMed Central

High-resolution Nuclear Magnetic Resonance (NMR) spectroscopy in combination with multivariate statistical methods has been widely used to investigate metabolic fluctuations in biological systems. This study presents three feature selection methods for identifying the metabolite features that contribute to the distinction of spectral samples among varying nutritional conditions in human plasma. Loading vectors of Principal Component Analysis (PCA), the optimal discriminant direction of Fisher discriminant analysis, and index values of the Variable Importance in Projection (VIP) in a Partial Least Square Discriminant Analysis (PLS-DA) were used to calculate the importance of individual metabolite feature in spectra. In addition, an Orthogonal Signal Correction (OSC) filter was used to eliminate unnecessary variations in NMR spectra and its effectiveness was demonstrated through PCA and kernel PCA. For the evaluation of presented feature selection methods, we compared the ability of classification based on the metabolite features selected by each method. The results have shown that the best classification was achieved using VIP values from an OSC-PLS-DA model. PMID:18767354

Cho, Hyun-Woo; Kim, Seoung Bum; Jeong, Myong K.; Park, Youngja; Gletsu, Nana; Ziegler, Thomas R.; Jones, Dean P.

2013-01-01

120

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

SciTech Connect

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

Chung, Sun-Ju; Hwang, Kyu-Ha; Ryu, Yoon-Hyun; Lee, Chung-Uk, E-mail: sjchung@kasi.re.kr, E-mail: kyuha@kasi.re.kr, E-mail: yhryu@kasi.re.kr, E-mail: leecu@kasi.re.kr [Korea Astronomy and Space Science Institute, Hwaam-Dong, Yuseong-Gu, Daejeon 305-348 (Korea, Republic of)

2012-05-20

121

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

PubMed Central

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

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

2011-01-01

122

Feature Selection for high Dimensional DNA Microarray data using hybrid approaches  

PubMed Central

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

Kumar, Ammu Prasanna; Valsala, Preeja

2013-01-01

123

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

PubMed

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

Kumar, Ammu Prasanna; Valsala, Preeja

2013-01-01

124

High-Velocity Absorption Features in FUSE Spectra of Eta Carinae  

NASA Technical Reports Server (NTRS)

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.

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

2003-01-01

125

CDK control of mitotic progression in Saccharomyces cerevisiae  

E-print Network

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 ...

Rahal, Rami S

2008-01-01

126

Identification of novel regulators of mitotic exit in Saccharomyces cerevisiae  

E-print Network

The division of a eukaryotic cell into two daughter cells is controlled by cyclin dependent kinase (CDK). Entry into mitosis is promoted by the activity of CDK complexed with mitotic cyclins. Upon faithful segregation of ...

D'Aquino, Katharine E

2006-01-01

127

Polymer Models of Meiotic and Mitotic Chromosomes  

PubMed Central

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

Marko, John F.; Siggia, Eric D.

1997-01-01

128

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

SciTech Connect

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

Komura, Jun-ichiro, E-mail: junkom@med.tohoku.ac.jp [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)] [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Ikehata, Hironobu [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)] [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan); Mori, Toshio [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan)] [Radioisotope Research Center, Nara Medical University, Kashihara, Nara 634-8521 (Japan); Ono, Tetsuya [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)] [Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)

2012-03-10

129

[Effect of Saccharomyces cerevisiae RAD54 mutation on gamma ray-induced reciprocal mitotic recombination].  

PubMed

The effect of gamma-irradiation on mitotic segregation and intergenic reciprocal mitotic recombination between the centromere and the ade2 locus of rad sensitive Saccharomyces mutant has been studied in comparison with the wild type RAD. These strains homozygous for either RAD or rad54 gene, showed gamma-rays induced mitotic segregation and reciprocal mitotic recombination. Within a dose range resulting in an equal survival, fraction induced mitotic segregation and intergenic reciprocal recombination was greater for the RAD strain. Rad54 mutation increased the spontaneous mitotic segregation and mitotic reciprocal recombination in comparison with the rad strain. PMID:7007162

Kasinova, G V

1980-01-01

130

Aurora B Regulates MCAK at the Mitotic Centromere  

Microsoft Academic Search

Chromosome orientation and alignment within the mitotic spindle requires the Aurora B protein kinase and the mitotic centromere-associated kinesin (MCAK). Here, we report the regulation of MCAK by Aurora B. Aurora B inhibited MCAK's microtubule depolymerizing activity in vitro, and phospho-mimic (S\\/E) mutants of MCAK inhibited depolymerization in vivo. Expression of either MCAK (S\\/E) or MCAK (S\\/A) mutants increased the

Paul D Andrews; Yulia Ovechkina; Nick Morrice; Michael Wagenbach; Karen Duncan; Linda Wordeman; Jason R Swedlow

2004-01-01

131

Loss of heterozygosity and mitotic linkage maps in the mouse.  

PubMed Central

Loss of heterozygosity is a significant oncogenetic mechanism and can involve a variety of mechanisms including chromosome loss, deletion, and homologous interchromosomal mitotic recombination. Analysis of H-2 antigen-loss variants from heterozygous murine cell lines provides an experimental system to estimate the relative contributions of different mechanisms for allele loss and to compare the chromosomal patterns of mitotic and meiotic recombination. Cytotoxic anti-H-2D antibodies and complement were used to isolate 161 independent target antigen-negative clones from H-2d/H-2b heterozygous cell lines; of these, 131 (84.5%) lost the allele encoding the target antigen. Allele-loss variants were typed and scored as either heterozygous or homozygous for six H-2D-proximal chromosome 17 markers and for one distal marker by restriction enzyme-site variations and Southern analysis. A single mitotic crossover could account for 50 clones (37%), with heterozygosity for at least one proximal marker and loss of heterozygosity for all markers distal to the putative recombination site. Eighty-two allele-loss variants (60%) were homozygous for all markers; the origin of these clones could be either chromosome loss or mitotic recombination between the centromere and the most proximal marker. Only 4 clones (3%) arose through more complex events such as multiple crossovers or deletion. A mitotic linkage map for mouse chromosome 17 was constructed, and the gene order deduced from somatic recombination was identical to that obtained by conventional transmission genetics. These results demonstrate that mitotic recombination is a common event leading to allele loss, in spite of the lack of evidence for frequent somatic pairing of homologous chromosomes. Mitotic mapping provides a defined system for comparison of mitotic and meiotic recombination and may lead to practical advances for elucidating somatic mechanisms of oncogenesis and for gene therapy in targeting mutations to specific sites through homologous recombination. Images PMID:1677769

Henson, V; Palmer, L; Banks, S; Nadeau, J H; Carlson, G A

1991-01-01

132

Feature extraction and normalization algorithms for high-density oligonucleotide gene expression array data  

Microsoft Academic Search

Algorithms for performing feature extraction and normalization on high-density oligonucleotide geneexpression arrays, have not been fully explored, and the impact these algorithms have on the downstream analysis is notwell understood. Advances in such low-level analysis methods are essential to increase the sensitivity and specificity ofdetecting whether genes are present and\\/or differentially expressed. We have developed and implemented a number ofalgorithms

Eric E. Schadt; Cheng Li; Byron Ellis; Wing H. Wong

2001-01-01

133

Systematic Phosphorylation Analysis of Human Mitotic Protein Complexes  

PubMed Central

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

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

2014-01-01

134

Systematic phosphorylation analysis of human mitotic protein complexes.  

PubMed

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 with the Aurora kinase B (AURKB) inhibitor Hesperadin and a new Polo-like 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 six proteins as direct candidate substrates of AURKB or PLK1. PMID:22067460

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

2011-01-01

135

High-order graph matching based feature selection for Alzheimer's disease identification.  

PubMed

One of the main limitations of l1-norm feature selection is that it focuses on estimating the target vector for each sample individually without considering relations with other samples. However, it's believed that the geometrical relation among target vectors in the training set may provide useful information, and it would be natural to expect that the predicted vectors have similar geometric relations as the target vectors. To overcome these limitations, we formulate this as a graph-matching feature selection problem between a predicted graph and a target graph. In the predicted graph a node is represented by predicted vector that may describe regional gray matter volume or cortical thickness features, and in the target graph a node is represented by target vector that include class label and clinical scores. In particular, we devise new regularization terms in sparse representation to impose high-order graph matching between the target vectors and the predicted ones. Finally, the selected regional gray matter volume and cortical thickness features are fused in kernel space for classification. Using the ADNI dataset, we evaluate the effectiveness of the proposed method and obtain the accuracies of 92.17% and 81.57% in AD and MCI classification, respectively. PMID:24579155

Liu, Feng; Suk, Heung-Il; Wee, Chong-Yaw; Chen, Huafu; Shen, Dinggang

2013-01-01

136

Distinctive Features of Novel Superconducting Transitions in Underdoped and Overdoped HIGH-Tc Cuprates  

NASA Astrophysics Data System (ADS)

It is argued that the new theory that combines the precursor BCS-like non-superconducting (SC) pairing and the Cooper-pair condensation into a superfluid Bose-liquid state is more plausible than the standard SC fluctuation approach in describing the distinctive features of the underdoped and overdoped high-Tc cuprates. We show that the scenarios for high-Tc superconductivity in these materials are quite different on the character of the Cooper-pair formation and SC phase transitions.

Dzhumanov, S.; Fan, J. D.

137

Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner.  

PubMed

Cell fate determination in the progeny of mammary epithelial stem/progenitor cells remains poorly understood. Here, we have examined the role of the mitotic kinase Aurora A (AURKA) in regulating the balance between basal and luminal mammary lineages. We find that AURKA is highly expressed in basal stem cells and, to a lesser extent, in luminal progenitors. Wild-type AURKA expression promoted luminal cell fate, but expression of an S155R mutant reduced proliferation, promoted basal fate, and inhibited serial transplantation. The mechanism involved regulation of mitotic spindle orientation by AURKA and the positioning of daughter cells after division. Remarkably, this was NOTCH dependent, as NOTCH inhibitor blocked the effect of wild-type AURKA expression on spindle orientation and instead mimicked the effect of the S155R mutant. These findings directly link AURKA, NOTCH signaling, and mitotic spindle orientation and suggest a mechanism for regulating the balance between luminal and basal lineages in the mammary gland. PMID:23810554

Regan, Joseph L; Sourisseau, Tony; Soady, Kelly; Kendrick, Howard; McCarthy, Afshan; Tang, Chan; Brennan, Keith; Linardopoulos, Spiros; White, Donald E; Smalley, Matthew J

2013-07-11

138

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

NASA Astrophysics Data System (ADS)

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

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

2013-12-01

139

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

.   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

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

140

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

NASA Astrophysics Data System (ADS)

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.

Sharghi, Elan

141

Plasma density features associated with strong convection in the winter high-latitude F region  

NASA Technical Reports Server (NTRS)

A single plasma convection model was combined with an ionospheric-atmospheric composition model to study plasma density features associated with string convection in the winter high-latitude F region. Time dependent, three-dimensional, ion density distributions for NO(+), O2(+), N2(+), O(+) and He(+) were produced, and the ionosphere above 42 deg N magnetic latitude was covered for 24 hours. The study found that for strong and weak convection, electron density exhibited a variation with altitude, latitude, longitude and universal time. Ionospheric features were evident for strong convection, but modified in comparison with those found for slow convection. Also found for strong convection was a more pronounced tongue of ionization, the appearance of a new polar hole in the polar cap, and a midlatitude electron density trough that was not as deep as found for a weak convection. In addition, good agreement was found between predictions and Atmosphere Explorer measurements of ion composition variation with latitude and local time.

Sojka, J. J.; Raitt, W. J.; Schunk, R. W.

1981-01-01

142

rough deal: a gene required for proper mitotic segregation in Drosophila  

PubMed Central

We describe a genetic locus rough deal (rod) in Drosophila melanogaster, identified by mutations that interfere with the faithful transmission of chromosomes to daughter cells during mitosis. Five mutant alleles were isolated, each associated with a similar set of mitotic abnormalities in the dividing neuroblasts of homozygous mutant larvae: high frequencies of aneuploid cells and abnormal anaphase figures, in which chromatids may lag, form bridges, or completely fail to separate. Surviving homozygous adults are sterile, and show cuticular defects associated with cell death, i.e., roughened eyes, sparse abdominal bristles, and notched wing margins. The morphological process of spermatogenesis is largely unaffected and motile sperm are produced, but meiocyte aneuploidy is common. The nature of the observed abnormalities in mitotic cells suggests that the reduced fidelity of chromosome transmission to the daughter cells is due to a failure in a mechanism involved in assuring the proper release of sister chromatids. PMID:2512302

1989-01-01

143

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

PubMed Central

Picropodophyllin (PPP) is an anticancer drug undergoing clinical development in NSCLC. PPP has been shown to suppress IGF-1R signaling and to induce a G2/M cell cycle phase arrest but the exact mechanisms remain to be elucidated. The present study identified an IGF-1-independent mechanism of PPP leading to pro-metaphase arrest. The mitotic block was induced in human cancer cell lines and in an A549 xenograft mouse but did not occur in normal hepatocytes/mouse tissues. Cell cycle arrest by PPP occurred in vitro and in vivo accompanied by prominent CDK1 activation, and was IGF-1R-independent since it occurred also in IGF-1R-depleted and null cells. The tumor cells were not arrested in G2/M but in mitosis. Centrosome separation was prevented during mitotic entry, resulting in a monopolar mitotic spindle with subsequent prometaphase-arrest, independent of Plk1/Aurora A or Eg5, and leading to cell features of mitotic catastrophe. PPP also increased soluble tubulin and decreased spindle-associated tubulin within minutes, indicating that it interfered with microtubule dynamics. These results provide a novel IGF-1R-independent mechanism of antitumor effects of PPP. PMID:25268741

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

2014-01-01

144

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

PubMed Central

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

Alawi, Faizan; Lin, Ping

2013-01-01

145

Viscous flow features on the surface of Mars: Observations from high-resolution Mars Orbiter Camera (MOC)  

E-print Network

Viscous flow features on the surface of Mars: Observations from high-resolution Mars Orbiter Camera-thick surface layer was identified in high-resolution (Mars Orbiter Camera (MOC) images. A global features. Slope angles derived from Mars Orbiter Laser Altimeter (MOLA) data, along with an experimentally

Head III, James William

146

The 'Double-Edged Sword' of high-feature products: an explorative study of the business impact  

Microsoft Academic Search

In high-technology consumer markets, manufacturers integrate a growing number of technologies and features to satisfy consumers' preference for high-feature products. At the same time, companies report an increasing number of consumer complaints and even product returns, not due to product faults but to usability problems and the product's inability to meet customer expectations. To investigate the potential business impact of

Jeroen Keijzers; Ouden den PH; Yuan Lu

2008-01-01

147

DESIGN SAFETY FEATURES OF THE BNL HIGH-TEMPERATURE COMBUSTION FACILITY  

SciTech Connect

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.

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

2000-06-11

148

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

USGS Publications Warehouse

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

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

1988-01-01

149

Robust mitotic entry is ensured by a latching switch  

PubMed Central

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

Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novak, Bela

2013-01-01

150

Robust mitotic entry is ensured by a latching switch.  

PubMed

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

Tuck, Chloe; Zhang, Tongli; Potapova, Tamara; Malumbres, Marcos; Novák, Béla

2013-01-01

151

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

PubMed

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

Bompard, Guillaume; Morin, Nathalie

2012-01-01

152

Automatic quantification of microtubule dynamics enables RNAi-screening of new mitotic spindle regulators.  

PubMed

The genetic integrity of every organism depends on the faithful partitioning of its genome between two daughter cells in mitosis. In all eukaryotes, chromosome segregation requires the assembly of the mitotic spindle, a bipolar array of dynamic microtubules. Perturbations in microtubule dynamics affect spindle assembly and maintenance and ultimately result in aberrant cell divisions. To identify new regulators of microtubule dynamics within the hundreds of mitotic hits, reported in RNAi screens performed in C. elegans, Drosophila and mammalian tissue culture cells [Sonnichsen et al., 2005; Goshima et al., 2007; Neumann et al., 2010], we established a fast and quantitative assay to measure microtubule dynamics in living cells. Here we present a fully automated workflow from RNAi transfection, via image acquisition and data processing, to the quantitative characterization of microtubule behaviour. Candidate genes are knocked down by solid-phase reverse transfection with siRNA oligos in HeLa cells stably expressing EB3-EGFP, a microtubule plus end marker. Mitotic cells are selected using an automatic classifier [Conrad et al., 2011] and imaged on a spinning disk confocal microscope at high temporal and spatial resolution. The time-lapse movies are analysed using a multiple particle tracking software, developed in-house, that automatically detects microtubule plus ends, tracks microtubule growth events over consecutive frames and calculates growth speeds, lengths and lifetimes of the tracked microtubules. The entire assay provides a powerful tool to analyse the effect of essential mitotic genes on microtubule dynamics in living cells and to dissect their contribution in spindle assembly and maintenance. PMID:21491614

Sironi, Lucia; Solon, Jérôme; Conrad, Christian; Mayer, Thomas U; Brunner, Damian; Ellenberg, Jan

2011-05-01

153

Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C.  

PubMed

Protein machines are multi-subunit protein complexes that orchestrate highly regulated biochemical tasks. An example is the anaphase-promoting complex/cyclosome (APC/C), a 13-subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome. Because blocking mitotic exit is an effective approach for inducing tumour cell death, the APC/C represents a potential novel target for cancer therapy. APC/C activation in mitosis requires binding of Cdc20 (ref. 5), which forms a co-receptor with the APC/C to recognize substrates containing a destruction box (D-box). Here we demonstrate that we can synergistically inhibit APC/C-dependent proteolysis and mitotic exit by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. We identify a small molecule, called apcin (APC inhibitor), which binds to Cdc20 and competitively inhibits the ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of apcin to block mitotic exit is synergistically amplified by co-addition of tosyl-l-arginine methyl ester, a small molecule that blocks the APC/C-Cdc20 interaction. This work suggests that simultaneous disruption of multiple, weak protein-protein interactions is an effective approach for inactivating a protein machine. PMID:25156254

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

2014-10-30

154

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

PubMed Central

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

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

2006-01-01

155

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

PubMed Central

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

Cote, G B; Gyftodimou, J

1991-01-01

156

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

PubMed Central

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

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

2000-01-01

157

Structural features of the behavior of a high-carbon pearlitic steel upon cyclic loading  

NASA Astrophysics Data System (ADS)

The structural evolution upon high-cycle fatigue (tension with the magnitude of stress in a cycle below the macroscopic yield stress) of the hypereutectoid steel U10 (1.03 wt % C), in which pearlite of different morphology (fine-lamellar, coarse-lamellar, and partially spheroidized pearlite) was formed, has been investigated by scanning and transmission electron microscopy. Based on the fractographic analysis, features of fracture of these structural states have been considered. At a significant distance (10 mm) from the fatigue fracture, features of structural transformations caused by cyclic loading have been revealed. It has been shown that upon high-cycle fatigue in the steel U10 with structures of lamellar and partially spheroidized pearlite, substantial structural changes occur, namely, fragmentation and partial dissolution of cementite plates, and in fine pearlite, additionally, spheroidizing of cementite and polygonization of the ferritic component are observed. A dependence of the character of fracture on the type of structure formed upon fatigue loading has been established. In the steel with a nonequilibrium structure of unannealed fine pearlite, an enhanced elasticity modulus, as compared to other more stable structures (coarse-lamellar, annealed fine, and spheroidized pearlite), and a reduction in the magnitude of the elasticity modulus under the action of cyclic loading have been found. It has been established that the structural changes in fine pearlite of laboratory specimens of the steel U10 upon cyclic tension are qualitatively similar to those in a railroad wheel of the steel 65G under the service conditions.

Makarov, A. V.; Savrai, R. A.; Schastlivtsev, V. M.; Tabatchikova, T. I.; Yakovleva, I. L.; Egorova, L. Yu.

2011-01-01

158

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

NASA Astrophysics Data System (ADS)

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

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

2010-04-01

159

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

NASA Astrophysics Data System (ADS)

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.

Li, Bangyu; Zhang, Hui; Xu, Fanjiang

2014-03-01

160

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

PubMed

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

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

2014-01-01

161

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

PubMed Central

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

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

162

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

PubMed Central

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

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

2014-01-01

163

Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae  

PubMed Central

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

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

2014-01-01

164

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

SciTech Connect

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.

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

165

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

166

Force and the spindle: Mechanical cues in mitotic spindle orientation  

PubMed Central

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

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

2014-01-01

167

The crystal structure of archaeal serine hydroxymethyltransferase reveals idiosyncratic features likely required to withstand high temperatures.  

PubMed

Serine hydroxymethyltransferases (SHMTs) play an essential role in one-carbon unit metabolism and are used in biomimetic reactions. We determined the crystal structure of free (apo) and pyridoxal-5'-phosphate-bound (holo) SHMT from Methanocaldococcus jannaschii, the first from a hyperthermophile, from the archaea domain of life and that uses H4 MPT as a cofactor, at 2.83 and 3.0 Å resolution, respectively. Idiosyncratic features were observed that are likely to contribute to structure stabilization. At the dimer interface, the C-terminal region folds in a unique fashion with respect to SHMTs from eubacteria and eukarya. At the active site, the conserved tyrosine does not make a cation-? interaction with an arginine like that observed in all other SHMT structures, but establishes an amide-aromatic interaction with Asn257, at a different sequence position. This asparagine residue is conserved and occurs almost exclusively in (hyper)thermophile SHMTs. This led us to formulate the hypothesis that removal of frustrated interactions (such as the Arg-Tyr cation-? interaction occurring in mesophile SHMTs) is an additional strategy of adaptation to high temperature. Both peculiar features may be tested by designing enzyme variants potentially endowed with improved stability for applications in biomimetic processes. Proteins 2014; 82:3437-3449. © 2014 Wiley Periodicals, Inc. PMID:25257552

Angelucci, Francesco; Morea, Veronica; Angelaccio, Sebastiana; Saccoccia, Fulvio; Contestabile, Roberto; Ilari, Andrea

2014-12-01

168

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

NASA Astrophysics Data System (ADS)

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

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

2014-01-01

169

Can High Performance Software DSM Systems Designed With InfiniBand Features Benefit from PCI-Express?  

E-print Network

Can High Performance Software DSM Systems Designed With InfiniBand Features Benefit from PCI and atomic op- erations have been used to implement some portions of the software DSM protocols directly-Express, on the perfor- mance of software DSM protocols which use the network features of InfiniBand. We can see

Panda, Dhabaleswar K.

170

Ion-neutral momentum coupling near discrete high-latitude ionospheric features  

NASA Technical Reports Server (NTRS)

A two-dimensional numerical model is developed to study the momentum coupling between the ionosphere and neutral atmosphere in the vicinity of discrete high-latitude features, such as convection channels and plasma density troughs. Based on generalized magnetohydrodynamic equations the model takes account of global pressure gradients, viscous dissipation, ion drag, the Coriolis force, and electrodynamic drifts. Among the findings of an initial steady state investigation are the following: (1) in convection channels, significant shears and rotations of the thermospheric flow can occur below 200 km if a minimum in the electron density profile is present between the E and F regions; (2) in convection channels, the thermospheric wind decreases with height in the F region owing to the effects of horizontal viscosity; and (3) at low altitudes, the boundaries of convection channels may produce Ekman spirals.

St-Maurice, J.-P.; Schunk, R. W.

1981-01-01

171

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

NASA Technical Reports Server (NTRS)

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.

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

172

A simple feature of yielding behavior of highly dense suspensions of soft micro-hydrogel particles.  

PubMed

The highly dense suspensions of soft micro-hydrogels with a narrow size distribution (typically ?eff > 0.9 where ?eff is the apparent volume fraction of the particle), which form a regular lattice structure, exhibit a simple feature in the yielding behavior: the yield strain ?c [ca. 2.5% and ca. 4.8% for poly(N-isopropylmethacrylamide) (PNIPMA) and poly(N-isopropylacrylamide) (PNIPA) hydrogel particles, respectively] is nearly insensitive to the cross-link concentration (cx), particle diameter (Dh), and particle concentration (c) in the limited c range examined here, and ?c is almost constant in a wide range of equilibrium shear moduli over two orders of magnitude. In addition, no appreciable difference in ?c is observed in the dense pastes with crystalline and glassy structures which are formed by mono- and bidisperse microgels, respectively. This is in contrast to a finite difference in ?c for the crystal and glass formed by the hard sphere reported by Koumakis et al. [Soft Matter, 4, 2008 (2008)]. Furthermore, the highly dense suspensions of NIPA core-NIPMA shell microgels are similar in ?c to those of NIPMA microgels. These results indicate that ?c for the highly dense suspensions of soft micro-hydrogels depends primarily on the kind of constituent polymer near the particle surface. The yield strain ?c is expected to be governed by short-range interactions such as adhesion and friction. PMID:25346296

Urayama, Kenji; Saeki, Taku; Cong, Shen; Uratani, Shota; Takigawa, Toshikazu; Murai, Masaki; Suzuki, Daisuke

2014-12-21

173

NuMA is required for the organization of microtubules into aster-like mitotic arrays  

Microsoft Academic Search

NuMA (Nuclear protein that associates with the Mitotic ~paratus) is a 235-kD intranuclear protein that accumulates at the pericentrosomal region of the mitotic spindle in vertebrate cells. To determine if NuMA plays an active role in organizing the microtu- bules at the polar region of the mitotic spindle, we have developed a cell free system for the assembly of mitotic

Tirso Gaglio; Alejandro Saredi; Duane A. Compton

1995-01-01

174

Bhlhb5 Regulates the Post-Mitotic Acquisition of Area Identities in Layers II-V of the Developing Neocortex  

PubMed Central

SUMMARY While progenitor-restricted factors broadly specify area identities in developing neocortex, the downstream regulatory elements involved in acquisition of those identities in post-mitotic neurons are largely unknown. Here, we identify Bhlhb5, a transcription factor expressed in layers II–V, as a post-mitotic regulator of area identity. Bhlhb5 is initially expressed in a high caudomedial to low rostrolateral gradient that transforms into a sharp border between sensory and rostral motor cortices. Bhlhb5-null mice exhibit aberrant expression of area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, Bhlhb5-null mice display post-synaptic disorganization of vibrissal barrels. In caudal motor cortex, Bhlhb5-null mice exhibit anomalous differentiation of corticospinal motor neurons, accompanied by failure of corticospinal tract formation. Together, these results demonstrate Bhlhb5’s function as an area-specific transcription factor that regulates the post-mitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and post-mitotic neurons driving neocortical arealization. PMID:18957218

Joshi, Pushkar S.; Molyneaux, Bradley J.; Feng, Liang; Xie, Xiaoling; Macklis, Jeffrey D.; Gan, Lin

2008-01-01

175

Mitotic lamin disassembly is triggered by lipid-mediated signaling  

PubMed Central

Disassembly of the nuclear lamina is a key step during open mitosis in higher eukaryotes. The activity of several kinases, including CDK1 (cyclin-dependent kinase 1) and protein kinase C (PKC), has been shown to trigger mitotic lamin disassembly, yet their precise contributions are unclear. In this study, we develop a quantitative imaging assay to study mitotic lamin B1 disassembly in living cells. We find that CDK1 and PKC act in concert to mediate phosphorylation-dependent lamin B1 disassembly during mitosis. Using ribonucleic acid interference (RNAi), we showed that diacylglycerol (DAG)-dependent PKCs triggered rate-limiting steps of lamin disassembly. RNAi-mediated depletion or chemical inhibition of lipins, enzymes that produce DAG, delayed lamin disassembly to a similar extent as does PKC inhibition/depletion. Furthermore, the delay of lamin B1 disassembly after lipin depletion could be rescued by the addition of DAG. These findings suggest that lipins activate a PKC-dependent pathway during mitotic lamin disassembly and provide evidence for a lipid-mediated mitotic signaling event. PMID:22986494

Mall, Moritz; Walter, Thomas; Gorjanacz, Matyas; Davidson, Iain F.; Nga Ly-Hartig, Thi Bach; Ellenberg, Jan

2012-01-01

176

A roller coaster ride with the mitotic cyclins  

Microsoft Academic Search

Cyclins are discovered as proteins that accumulate progressively through interphase and disappear abruptly at mitosis during each cell cycle. In mammalian cells, cyclin A accumulates from late G1 phase and is destroyed before metaphase, and cyclin B is destroyed slightly later at anaphase. The abundance of the mitotic cyclins is mainly regulated at the levels of transcription and proteolysis. Transcription

Tsz Kan Fung; Randy Y. C. Poon

2005-01-01

177

Parameters of mitotic recombination in minute mutants of Drosophila melanogaster  

Microsoft Academic Search

A sample of 16 Minutes, representing 12 loci distributed over all the chromo- some arms and including 3 pairs of alleles and 4 deficiencies, has been studied with respect to several developmental and recombinational parameters. Cell marker mutants located in most of the chromosome arms were used to assess (1) spontaneous and X-ray-induced mitotic recombination fiequencies of each Minute, and

A. FERRUS

1975-01-01

178

Occludin Localizes to Centrosomes and Modifies Mitotic Entry*  

PubMed Central

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

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

2011-01-01

179

Caspase3-mediated degradation of condensin Cap-H regulates mitotic cell death  

Microsoft Academic Search

Mitotic death is a major form of cell death in cancer cells that have been treated with chemotherapeutic drugs. However, the mechanisms underlying this form of cell death is poorly understood. Here, we report that the loss of chromosome integrity is an important determinant of mitotic death. During prolonged mitotic arrest, caspase-3 is activated and it cleaves Cap-H, a subunit

S-K Lai; C-H Wong; Y-P Lee; H-Y Li

2011-01-01

180

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

NASA Technical Reports Server (NTRS)

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.

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

2001-01-01

181

Detailed Hydrographic Feature Extraction from High-Resolution LiDAR Data  

SciTech Connect

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

Danny L. Anderson

2012-05-01

182

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

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

183

High-spectral resolution observations of the 3.29 micron emission feature: Comparison to QCC and PAHs  

NASA Technical Reports Server (NTRS)

Two of the most promising explanations for the origin of the interstellar emission features observed at 3.29, 3.4, 6.2, 7.7, 8.6, and 11.3 microns are: quenched carbonaceous composite (QCC) and polycyclic aromatic hydrocarbons (PAHs). High resolution spectra are given of the 3.29 micron emission feature which were taken with the Cooled Grating Array Spectrometer at the NASA Infrared Telescope Facility and previously published. These spectra show that the peak wavelength of the 3.29 micron feature is located at 3.295 + or - 0.005 micron and that it is coincident with the peak absorbance of QCC. The peak wavelength of the 3.29 micron feature appears to be the same in all of the sources observed thus far. However, the width of the feature in HD 44179 and Elias 1 is only 0.023 micron, which is smaller than the 0.043 micron width in NGC 7027, IRAS 21282+5050, the Orion nebula, and BD+30 deg 3639. Spectra of NGC 7027, QCC, and PAHs is shown. QCC matches the 3.29 micron interstellar emission feature very closely in the wavelength of the peak, and it produces a single feature. On the other hand, PAHs rarely match the peak of the interstellar emission feature, and characteristically produce multiple features.

Tokunaga, Alan T.; Sellgren, Kris; Sakata, Akira; Wada, S.; Onaka, Takashi; Nakada, Y.; Nagata, T.

1989-01-01

184

Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function  

PubMed Central

In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in leukemia and solid tumor-derived cells identified by their morphology, DNA content and mitotic marker analyses. Pharicin A-induced mitotic arrest is associated with unaligned chromosomes, aberrant BubR1 localization and deregulated spindle checkpoint activation. Pharicin A directly binds to BubR1 in vitro, which is correlated with premature sister chromatid separation in vivo. Pharicin A also induces mitotic arrest in paclitaxel-resistant Jurkat and U2OS cells. Combined, our study strongly suggests that pharicin A represents a novel class of small molecule compounds capable of perturbing mitotic progression and initiating mitotic catastrophe, which merits further preclinical and clinical investigations for cancer drug development. PMID:20603598

Huang, Ying; Wu, Ying-Li; Zhao, Yong; Xiao, Wei-Lie; Lin, Qi-Shan; Sun, Han-Dong

2010-01-01

185

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

PubMed

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

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

2014-03-01

186

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

PubMed Central

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

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

2014-01-01

187

Universal features in the photoemission spectroscopy of high-temperature superconductors  

PubMed Central

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

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

188

RHAMM Promotes Interphase Microtubule Instability and Mitotic Spindle Integrity through MEK1/ERK1/2 Activity*  

PubMed Central

An oncogenic form of RHAMM (receptor for hyaluronan-mediated motility, mouse, amino acids 163–794 termed RHAMM?163) is a cell surface hyaluronan receptor and mitotic spindle protein that is highly expressed in aggressive human cancers. Its regulation of mitotic spindle integrity is thought to contribute to tumor progression, but the molecular mechanisms underlying this function have not previously been defined. Here, we report that intracellular RHAMM?163 modifies the stability of interphase and mitotic spindle microtubules through ERK1/2 activity. RHAMM?/? mouse embryonic fibroblasts exhibit strongly acetylated interphase microtubules, multi-pole mitotic spindles, aberrant chromosome segregation, and inappropriate cytokinesis during mitosis. These defects are rescued by either expression of RHAMM or mutant active MEK1. Mutational analyses show that RHAMM?163 binds to ?- and ?-tubulin protein via a carboxyl-terminal leucine zipper, but in vitro analyses indicate this interaction does not directly contribute to tubulin polymerization/stability. Co-immunoprecipitation and pulldown assays reveal complexes of RHAMM?163, ERK1/2-MEK1, and ?- and ?-tubulin and demonstrate direct binding of RHAMM?163 to ERK1 via a D-site motif. In vitro kinase analyses, expression of mutant RHAMM?163 defective in ERK1 binding in mouse embryonic fibroblasts, and blocking MEK1 activity collectively confirm that the effect of RHAMM?163 on interphase and mitotic spindle microtubules is mediated by ERK1/2 activity. Our results suggest a model wherein intracellular RHAMM?163 functions as an adaptor protein to control microtubule polymerization during interphase and mitosis as a result of localizing ERK1/2-MEK1 complexes to their tubulin-associated substrates. PMID:20558733

Tolg, Cornelia; Hamilton, Sara R.; Morningstar, Lyndsey; Zhang, Jing; Zhang, S.; Esguerra, Kenneth V.; Telmer, Patrick G.; Luyt, Len G.; Harrison, Rene; McCarthy, James B.; Turley, Eva A.

2010-01-01

189

RHAMM promotes interphase microtubule instability and mitotic spindle integrity through MEK1/ERK1/2 activity.  

PubMed

An oncogenic form of RHAMM (receptor for hyaluronan-mediated motility, mouse, amino acids 163-794 termed RHAMM(Delta163)) is a cell surface hyaluronan receptor and mitotic spindle protein that is highly expressed in aggressive human cancers. Its regulation of mitotic spindle integrity is thought to contribute to tumor progression, but the molecular mechanisms underlying this function have not previously been defined. Here, we report that intracellular RHAMM(Delta163) modifies the stability of interphase and mitotic spindle microtubules through ERK1/2 activity. RHAMM(-/-) mouse embryonic fibroblasts exhibit strongly acetylated interphase microtubules, multi-pole mitotic spindles, aberrant chromosome segregation, and inappropriate cytokinesis during mitosis. These defects are rescued by either expression of RHAMM or mutant active MEK1. Mutational analyses show that RHAMM(Delta163) binds to alpha- and beta-tubulin protein via a carboxyl-terminal leucine zipper, but in vitro analyses indicate this interaction does not directly contribute to tubulin polymerization/stability. Co-immunoprecipitation and pulldown assays reveal complexes of RHAMM(Delta163), ERK1/2-MEK1, and alpha- and beta-tubulin and demonstrate direct binding of RHAMM(Delta163) to ERK1 via a D-site motif. In vitro kinase analyses, expression of mutant RHAMM(Delta163) defective in ERK1 binding in mouse embryonic fibroblasts, and blocking MEK1 activity collectively confirm that the effect of RHAMM(Delta163) on interphase and mitotic spindle microtubules is mediated by ERK1/2 activity. Our results suggest a model wherein intracellular RHAMM(Delta163) functions as an adaptor protein to control microtubule polymerization during interphase and mitosis as a result of localizing ERK1/2-MEK1 complexes to their tubulin-associated substrates. PMID:20558733

Tolg, Cornelia; Hamilton, Sara R; Morningstar, Lyndsey; Zhang, Jing; Zhang, S; Esguerra, Kenneth V; Telmer, Patrick G; Luyt, Len G; Harrison, Rene; McCarthy, James B; Turley, Eva A

2010-08-20

190

Binding of multiple features in memory by high-functioning adults with autism spectrum disorder.  

PubMed

Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) would be tested in a later memory test. In a second experiment, participants studied similar grids and were told that they would be tested on object-location or object-colour combinations. Recognition of combinations was significantly diminished in ASD, which survived covarying performance on the Color Trails Test (D'Elia et al. Color trails test. Professional manual. Psychological Assessment Resources, Lutz, 1996), a test of executive difficulties. The findings raise the possibility that medial temporal as well as frontal lobe processes are dysfunctional in ASD. PMID:24696375

Bowler, Dermot M; Gaigg, Sebastian B; Gardiner, John M

2014-09-01

191

High resolution seismic reflection profiles of Holocene volcanic and tectonic features, Mono Lake, California  

NASA Astrophysics Data System (ADS)

The Inyo-Mono Craters of Long Valley and Mono Basin, California are the youngest eruptive vents of the Great Basin, USA and the second youngest in California. They are one of two seismically active volcanic centers with geothermal power production in the Walker Lane, western Great Basin, the other being the Coso Volcanic Field to the south. High resolution seismic reflection data collected from the northern tip of the Mono Craters eruptive centers in Mono Lake delinates two structural zones proximal to the active volcanic centers in Mono Lake. A growth structure drapped by ~30 m or more of bedded sediment shows increasing deformation and offset of clastic deposits on the northwest margin of the basin. Coherent thin-bedded stratigraphic sections with strong reflectors to 30-100m depth are preserved on the western and northern margins of the basin. The southern and southeastern areas of the lake are generally seismically opaque, due to extensive ash and tephra deposits as well as widespread methane. Thin pockets of well-bedded, poorly consolidated sediment of probable Holocene and last glacial age are present within intrabasin depressions providing some local age constraints on surfaces adjacent to volcanic vents and volcanically modified features.

Jayko, A. S.; Hart, P. E.; Bursik, M. I.; McClain, J. S.; Moore, J. C.; Boyle, M.; Childs, J. R.; Novick, M.; Hill, D. P.; Mangan, M.; Roeske, S.

2009-12-01

192

Pores and Ridges: High-Resolution Fingerprint Matching Using Level 3 Features  

Microsoft Academic Search

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.

Anil K. Jain; Yi Chen; Meltem Demirkus

2007-01-01

193

Pores and Ridges: High-Resolution Fingerprint Matching Using Level 3 Features  

Microsoft Academic Search

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

Anil K. Jain; Yi Chen; Meltem Demirkus

2007-01-01

194

Molecular pathways regulating mitotic spindle orientation in animal cells.  

PubMed

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

Lu, Michelle S; Johnston, Christopher A

2013-05-01

195

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

NASA Astrophysics Data System (ADS)

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.

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

2005-05-01

196

Listeria bacteriophage peptidoglycan hydrolases feature high thermoresistance and reveal increased activity after divalent metal cation substitution.  

PubMed

The ability of the bacteriophage-encoded peptidoglycan hydrolases (endolysins) to destroy Gram-positive bacteria from without makes these enzymes promising antimicrobials. Recombinant endolysins from Listeria monocytogenes phages have been shown to rapidly lyse and kill the pathogen in all environments. To determine optimum conditions regarding application of recombinant Listeria phage endolysins in food or production equipments, properties of different Listeria endolysins were studied. Optimum NaCl concentration for the amidase HPL511 was 200 nM and 300 mM for the peptidases HPL118, HPL500, and HPLP35. Unlike most other peptidoglycan hydrolases, all four enzymes exhibited highest activity at elevated pH values at around pH 8-9. Lytic activity was abolished by EDTA and could be restored by supplementation with various divalent metal cations, indicating their role in catalytic function. While substitution of the native Zn(2+) by Ca(2+) or Mn(2+) was most effective in case of HPL118, HPL500, and HPLP35, supplementation with Co(2+) and Mn(2+) resulted in an approximately 5-fold increase in HPL511 activity. Interestingly, the glutamate peptidases feature a conserved SxHxxGxAxD zinc-binding motif, which is not present in the amidases, although they also require centrally located divalent metals for activity. The endolysins HPL118, HPL511, and HPLP35 revealed a surprisingly high thermostability, with up to 35% activity remaining after 30 min incubation at 90°C. The available data suggest that denaturation at elevated temperatures is reversible and may be followed by rapid refolding into a functional state. PMID:21720825

Schmelcher, Mathias; Waldherr, Florian; Loessner, Martin J

2012-01-01

197

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

PubMed Central

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

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

2014-01-01

198

Mitotic indexes as prognostic predictors in female breast cancer  

Microsoft Academic Search

Summary A series of 688 women with breast cancer were followed-up for a mean of 13 years. Tumour size, axillary lymph node status, histological grade, histological type and two mitotic indexes (M\\/V; MAI) were assessed and related to disease outcome. Primary tumour size (PPP=0.0001), and histological grade (P=0.0074) predicted axillary lymph node status. Recurrence as well as recurrence-free survival was

S. Aaltomaa; P. Lipponen; M. Eskelinen; V.-M. Kosma; S. Marin; E. Alhava; K. Syrjänen

1992-01-01

199

High resolution as a key feature to perform accurate ELISPOT measurements using Zeiss KS ELISPOT readers.  

PubMed

The enzyme-linked immunospot (ELISPOT) assay was originally developed for the detection of individual antibody secreting B-cells. Since then, the method has been improved, and ELISPOT is used for the determination of the production of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, or various interleukins (IL)-4, IL-5. ELISPOT measurements are performed in 96-well plates with nitrocellulose membranes either visually or by means of image analysis. Image analysis offers various procedures to overcome variable background intensity problems and separate true from false spots. ELISPOT readers offer a complete solution for precise and automatic evaluation of ELISPOT assays. Number, size, and intensity of each single spot can be determined, printed, or saved for further statistical evaluation. Cytokine spots are always round, but because of floating edges with the background, they have a nonsmooth borderline. Resolution is a key feature for a precise detection of ELISPOT. In standard applications shape and edge steepness are essential parameters in addition to size and color for an accurate spot recognition. These parameters need a minimum spot diameter of 6 pixels. Collecting one single image per well with a standard color camera with 750 x 560 pixels will result in a resolution much too low to get all of the spots in a specimen. IFN-gamma spots may have only 25 microm diameters, and TNF-alpha spots just 15 microm. A 750 x 560 pixel image of a 6-mm well has a pixel size of 12 microm, resulting in only 1 or 2 pixel for a spot. Using a precise microscope optic in combination with a high resolution (1300 x 1030 pixel) integrating digital color camera, and at least 2 x 2 images per well will result in a pixel size of 2.5 microm and, as a minimum, 6 pixel diameter per spot. New approaches try to detect two cytokines per cell at the same time (i.e., IFN-gamma and IL-5). Standard staining procedures produce brownish spots (horseradish peroxidase) and blue spots (alkaline phosphatase). Problems may occur with color overlaps from cells producing both cytokines, resulting in violet spots. The latest experiments therefore try to use fluorescence labels as a marker. Fluorescein isothiocyanate results in green spots and Rhodamine in red spots. Cells producing both cytokines appear yellow. These colors can be separated much easier than the violet, red, and blue, especially using a high resolution. PMID:15937349

Malkusch, Wolf

2005-01-01

200

Doublecortin induces mitotic microtubule catastrophe and inhibits glioma cell invasion  

PubMed Central

Doublecortin (DCX) is a microtubule binding protein that induces growth arrest at the G2-M phase of cell-cycle in glioma and suppresses tumor xenograft in immunocompromised hosts. DCX expression was found in neuronal cells, but lacking in glioma cells. We tested the hypothesis that DCX inhibits glioma U87 cell mitosis and invasion. Our data showed that DCX synthesizing U87 cells underwent mitotic microtubule spindle catastrophe in a neurabin II dependent pathway. Synthesis of both DCX and neurabin II were required to induce apoptosis in U87 and HEK 293T cells. In DCX expressing U87 cells, association of phosphorylated DCX (P-DCX) with protein phosphatase-1 (PP1) in the cytosol disrupted the interaction between kinesin-13 and PP1 in the nucleus and yielded spontaneously active kinesin-13. The activated kinesin-13 caused mitotic microtubule catastrophe in spindle checkpoint. P-DCX induced depolymerization of actin filaments in U87 cells, downregulated matrix metalloproteinase -2 (MMP-2) and MMP-9, and inhibited glioma U87 cell invasion in a neurabin II dependent pathway. Thus, localization of the DCX-neurabin II-PP1 complex in the cytosol of U87 tumor cells inhibited PP1 phosphatase activities leading to anti-glioma effects via 1) mitotic microtubule spindle catastrophe that blocks mitosis, and 2) depolymerization of actin that inhibits glioma cell invasion. PMID:19094064

Santra, Manoranjan; Santra, Sutapa; Roberts, Cindi; Zhang, Rui Lan; Chopp, Michael

2009-01-01

201

Pulling it together: The mitotic function of TACC3.  

PubMed

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

Hood, Fiona E; Royle, Stephen J

2011-05-01

202

Trichomonas vaginalis: chromatin and mitotic spindle during mitosis.  

PubMed

The mitotic phases and the changes that the chromatin and mitotic microtubules undergo during mitosis in the sexually transmitted parasite Trichomonas vaginalis are described. Parasites arrested in the gap 2 phase of the cell cycle by nutrient starvation were induced to mitosis by addition of fresh whole medium. [(3)H] Thymidine labeling of trichomonad parasites for 24 h showed that parasites have at least four synchronic duplications after mitosis induction. Fixed or live and acridine orange (AO)-stained trichomonads analyzed at different times during mitosis by epifluorescence microscopy showed that mitosis took about 45 min and is divided into five stages: prophase, metaphase, early and late anaphase, early and late telophase, and cytokinesis. The AO-stained nucleus of live trichomonads showed green (DNA) and orange (RNA) fluorescence, and the nucleic acid nature was confirmed by DNase and RNase treatment, respectively. The chromatin appeared partially condensed during interphase. At metaphase, it appeared as six condensed chromosomes, as recently reported, which decondensed at anaphase and migrated to the nuclear poles at telophase. In addition, small bundles of microtubules (as hemispindles) were detected only in metaphase with the polyclonal antibody anti-Entamoeba histolytica alpha-tubulin. This antibody showed that the hemispindle and an atractophore-like structure seem to duplicate and polarize during metaphase. In conclusion, T. vaginalis mitosis involves five mitotic phases in which the chromatin undergoes different degrees of condensation, from chromosomes to decondensed chromatin, and two hemispindles that are observed only in the metaphase stage. PMID:11162363

Gómez-Conde, E; Mena-López, R; Hernández-Jaúregui, P; González-Camacho, M; Arroyo, R

2000-11-01

203

SUMOylation inhibits FOXM1 activity and delays mitotic transition.  

PubMed

The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response. PMID:24362530

Myatt, S S; Kongsema, M; Man, C W-Y; Kelly, D J; Gomes, A R; Khongkow, P; Karunarathna, U; Zona, S; Langer, J K; Dunsby, C W; Coombes, R C; French, P M; Brosens, J J; Lam, E W-F

2014-08-21

204

The overlooked greatwall: a new perspective on mitotic control  

PubMed Central

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

Glover, David M.

2012-01-01

205

The overlooked greatwall: a new perspective on mitotic control.  

PubMed

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

Glover, David M

2012-03-01

206

Cloud field classification based upon high spatial resolution textural features. I - Gray level co-occurrence matrix approach  

NASA Technical Reports Server (NTRS)

Stratocumulus, cumulus, and cirrus clouds were identified on the basis of cloud textural features which were derived from a single high-resolution Landsat MSS NIR channel using a stepwise linear discriminant analysis. It is shown that, using this method, it is possible to distinguish high cirrus clouds from low clouds with high accuracy on the basis of spatial brightness patterns. The largest probability of misclassification is associated with confusion between the stratocumulus breakup regions and the fair-weather cumulus.

Welch, R. M.; Sengupta, S. K.; Chen, D. W.

1988-01-01

207

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

PubMed

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

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

2014-11-15

208

The ant colony algorithm for feature selection in high-dimension gene expression data for disease classification.  

PubMed

The use of gene expression data to diagnose complex diseases represents an exciting area of medicine; however, such data sets are often noisy, requiring the selection of feature subsets to obtain maximum classification accuracy. Due to the high dimensions of many expression data sets, filter-based methods are commonly used, but often yield inconsistent results. Optimization algorithms can outperform filter methods, but often require preselection of features to achieve good results. To address the problems of many commonly used feature selection methods, the ant colony algorithm (ACA) is proposed for use on data sets with large numbers of features. The ACA is an optimization algorithm capable of incorporating prior information, allowing it to search the sample space more efficiently than other optimization methods. When applied to several high-dimensional data sets, the ACA was able to identify small subsets of highly predictive and biologically relevant genes without the need for extensive preselection of features. Using the selected genes to train a latent variable model yielded substantial increases in prediction accuracy when compared to several rank-based methods and results obtained in previous studies. The superiority of the ACA algorithm was validated through simulation. PMID:18296718

Robbins, K R; Zhang, W; Bertrand, J K; Rekaya, R

2007-12-01

209

Fission yeast pkl1 is a kinesin-related protein involved in mitotic spindle function.  

PubMed Central

We have used anti-peptide antibodies raised against highly conserved regions of the kinesin motor domain to identify kinesin-related proteins in the fission yeast Schizosaccharomyces pombe. Here we report the identification of a new kinesin-related protein, which we have named pkl1. Sequence homology and domain organization place pkl1 in the Kar3/ncd subfamily of kinesin-related proteins. Bacterially expressed pkl1 fusion proteins display microtubule-stimulated ATPase activity, nucleotide-sensitive binding, and bundling of microtubules. Immunofluorescence studies with affinity-purified antibodies indicate that the pkl1 protein localizes to the nucleus and the mitotic spindle. Pkl1 null mutants are viable but have increased sensitivity to microtubule-disrupting drugs. Disruption of pkl1+ suppresses mutations in another kinesin-related protein, cut7, which is known to act in the spindle. Overexpression of pkl1 to very high levels causes a similar phenotype to that seen in cut7 mutants: V-shaped and star-shaped microtubule structures are observed, which we interpret to be spindles with unseparated spindle poles. These observations suggest that pkl1 and cut7 provide opposing forces in the spindle. We propose that pkl1 functions as a microtubule-dependent motor that is involved in microtubule organization in the mitotic spindle. Images PMID:8898367

Pidoux, A L; LeDizet, M; Cande, W Z

1996-01-01

210

The Spo12 protein of Saccharomyces cerevisiae: a regulator of mitotic exit whose cell cycle-dependent degradation is mediated by the anaphase-promoting complex.  

PubMed Central

The Spo12 protein plays a regulatory role in two of the most fundamental processes of biology, mitosis and meiosis, and yet its biochemical function remains elusive. In this study we concentrate on the genetic and biochemical analysis of its mitotic function. Since high-copy SPO12 is able to suppress a wide variety of mitotic exit mutants, all of which arrest with high Clb-Cdc28 activity, we speculated whether SPO12 is able to facilitate exit from mitosis when overexpressed by antagonizing mitotic kinase activity. We show, however, that Spo12 is not a potent regulator of Clb-Cdc28 activity and can function independently of either the cyclin-dependent kinase inhibitor (CDKi), Sic1, or the anaphase-promoting complex (APC) regulator, Hct1. Spo12 protein level is regulated by the APC and the protein is degraded in G1 by an Hct1-dependent mechanism. We also demonstrate that in addition to localizing to the nucleus Spo12 is a nucleolar protein. We propose a model where overexpression of Spo12 may lead to the delocalization of a small amount of Cdc14 from the nucleolus, resulting in a sufficient lowering of mitotic kinase levels to facilitate mitotic exit. Finally, site-directed mutagenesis of highly conserved residues in the Spo12 protein sequence abolishes both its mitotic suppressor activity as well as its meiotic function. This result is the first indication that Spo12 may carry out the same biochemical function in mitosis as it does in meiosis. PMID:11729145

Shah, R; Jensen, S; Frenz, L M; Johnson, A L; Johnston, L H

2001-01-01

211

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

PubMed

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

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

2011-02-28

212

High-resolution spectral features observed in the inner radiation belt trapped electron population  

SciTech Connect

Fine resolution measurements from the P78-1 satellite of 68- to 1120-keV electrons trapped at the lower L shell edge of the inner radiation belt have provided additional information on the previous discovery (Imhof and Smith, 1965) of the occurrences of peaks in the energy spectra. In some cases the data have yielded upper limits on the widths of the peaks as small as 26 keV. The energies of the peaks decrease slowly with increasing L value at a rate such that the calculated longitude drift periods remain nearly the same over the full L shell range for which they appear: often from approx.1.2 to approx.1.4 but occasionally up to L shells as high as approx.2.2. These peaks are frequently observed at approx.600-km altitude in the more durably trapped electron population having minimum drift altitudes of 100 km or greater and are to be contrasted with peaks in the quasi-trapped electrons precipitating from the inner belt at Lapprox. =(1.5-1.85) that decrease in energy much more rapidly with increasing L value (Imhof et al., 1974, 1978; Vampola and Kuck, 1978). The spectra at the lower edge of the inner belt often contain sharp features which are continually changing, perhaps as a result of new injections and/or redistributions and the rapid loss of trapped electrons due to atmospheric scattering. For the narrow peaks the observed small but significant changes in central energy with L value that maintain a constant longitude drift period are consistent with the previous interpretation of the nearly monoenergetic electrons trapped on a given L shell resulting from a redistribution of electrons trapped on somewhat higher L shells (Imhof et al., 1966; Cladis, 1966). In that hypothesis the energy selectivity was postulated to result from a quasi-resonance process whereby the electrons were accelerated as a result of the geomagnetic fluctuations that had periods comparable to the azimuthal drift periods of the electrons.

Imhof, W.L.; Gaines, E.E.; Reagan, J.B.

1981-04-01

213

Vandalism Detection in Wikipedia: A High-Performing, FeatureRich Model and its Reduction Through Lasso  

E-print Network

Vandalism Detection in Wikipedia: A High-Performing, Feature­Rich Model and its Reduction Through, such as Wikipedia, are so popular that they have become a favorite target of spammers and other vandals. In such popular sites, human vigilance is not enough to combat vandalism, and tools that detect possible vandalism

McDonald, David W.

214

Can High Performance Software DSM Systems Designed With InfiniBand Features Benefit from PCI-Express?  

E-print Network

Can High Performance Software DSM Systems Designed With InfiniBand Features Benefit from PCI;Presentation Outline · Introduction and Motivation · I/O Interconnection Technologies · DSM Protocols · Experimental Results · Conclusions and Future Work #12;Introduction · DSM Protocols ­ Communication intensive

Panda, Dhabaleswar K.

215

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

PubMed

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

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

2013-12-01

216

TPX2 regulates the localization and activity of Eg5 in the mammalian mitotic spindle  

PubMed Central

Mitotic spindle assembly requires the regulated activity of numerous spindle-associated proteins. In mammalian cells, the Kinesin-5 motor Eg5 interacts with the spindle assembly factor TPX2, but how this interaction contributes to spindle formation and function is not established. Using bacterial artificial chromosome technology, we generated cells expressing TPX2 lacking the Eg5 interaction domain. Spindles in these cells were highly disorganized with multiple spindle poles. The TPX2–Eg5 interaction was required for kinetochore fiber formation and contributed to Eg5 localization to spindle microtubules but not spindle poles. Microinjection of the Eg5-binding domain of TPX2 resulted in spindle elongation, indicating that the interaction of Eg5 with TPX2 reduces motor activity. Consistent with this possibility, we found that TPX2 reduced the velocity of Eg5-dependent microtubule gliding, inhibited microtubule sliding, and resulted in the accumulation of motor on microtubules. These results establish a novel function of TPX2 in regulating the location and activity of the mitotic motor Eg5. PMID:21969468

Ma, Nan; Titus, Janel; Gable, Alyssa; Ross, Jennifer L.

2011-01-01

217

Ectopic mitotic recombination in Drosophila probed with bacterial beta-galactosidase gene-based reporter transgenes.  

PubMed Central

Plasmids were constructed to investigate homologous mitotic recombination in Drosophila cells. Heteroalleles containing truncated but overlapping segments of the bacterial beta-galactosidase gene (lacZ) were positioned either on separate plasmids or as direct repeats on the same chromosome. Recombination reconstituted a functional lacZgene leading to expression of LacZ+activity detectable by histochemical staining. High extrachromosomal recombination (ECR) frequencies between unlinked heteroalleles were observed upon transient co-transfection into Drosophila melanogaster Schneider line 2 (S2) cells. Stably transfected cells containing the lacZ heteroalleles linked on a chromosome exhibited intrachromosomal recombination (ICR) frequencies two orders of magnitude lower than ECR frequencies. Recombination was inducible by exposing the cells to ethyl methanesulphonate or mitomycin C. Recombination products were characterized by multiplex PCR analysis and unequal sister chromatid recombination was found as the predominant mechanism reconstituting the lacZ gene. To investigate recombination in vivo imaginal disc cells from transgenic larvae carrying the reporter gene on the X chromosome were isolated and stained for LacZ+ activity. The presence of a few LacZ+ clones indicated that mitotic recombination events occurred at frequencies two orders of magnitude lower than the corresponding event in cultured cells and late during larval development. PMID:9380517

Bartsch, S; Ducker, K; Wurgler, F E; Sengstag, C

1997-01-01

218

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

SciTech Connect

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

Rubin, N.H.

1982-01-01

219

Feature extraction Feature extraction  

E-print Network

(hyperspectral sensors) Meteosat thermal IR channel hyperspectral "image cube" #12;Raw intensities · ProsFeature extraction #12;Feature extraction · Image interpretation: extract information from images · but the desired information may not be explicit in the raw observed pixel intensities · Transform image to make

Giger, Christine

220

Feature extraction Feature extraction  

E-print Network

(hyperspectral sensors) Meteosat thermal IR channel hyperspectral "image cube" #12;Raw intensities ! � ProsFeature extraction #12;Feature extraction ! � Image interpretation: extract information from images � but the desired information may not be explicit in the raw observed pixel intensities � Transform image to make

Giger, Christine

221

Abnormal crowd behavior detection using high-frequency and spatio-temporal features  

Microsoft Academic Search

Abnormal crowd behavior detection is an important research issue in computer vision. The traditional methods first extract\\u000a the local spatio-temporal cuboid from video. Then the cuboid is described by optical flow or gradient features, etc. Unfortunately,\\u000a because of the complex environmental conditions, such as severe occlusion, over-crowding, etc., the existing algorithms cannot\\u000a be efficiently applied. In this paper, we derive

Bo Wang; Mao Ye; Xue Li; Fengjuan Zhao; Jian Ding

222

Analysis and design of a high power factor, single-stage electronic ballast with dimming feature  

Microsoft Academic Search

The analysis, design and practical consideration of a single-stage electronic ballast with a dimming feature and unity power factor are presented in this paper. The proposed single-stage ballast is the combination of a boost power converter and a half-bridge series-resonant parallel-loaded inverter. The boost semi-stage, working in the discontinuous conduction mode, functions as a power factor corrector and the inverter

T.-F. Wu; M.-C. Chiang; E.-B. Chang

1997-01-01

223

Suppression of ser/thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death  

PubMed Central

Fostriecin is a natural product purified from Sterptomyces extracts with antitumor activity sufficient to warrant human clinical trials. Unfortunately, difficulties associated with supply and stable drug formulation stalled further development. At a molecular level, fostriecin is known to act as a catalytic inhibitor of four PPP-family-phosphatases, and reports describing the syntheses of designed molecules in the class suggest derivatives targeting enzymes within the fostriecin sensitive sub-family can be produced. However, it is not clear if the tumor selective cytotoxicity of fostriecin results from the inhibition of a specific phosphatase, multiple phosphatases, or a limited subset of fostriecin sensitive phosphatases. How the inhibition of sensitive phosphatases contributes to tumor selective cytotoxicity is also not clear. Here, high-content time-lapse imaging of live cells reveals novel insight into the cellular actions of fostriecin, showing that fostriecin induced apoptosis is not simply induced following a sustained mitotic arrest. Rather, apoptosis occurs in an apparent second interphase produced when tetraploid cells undergo mitotic slippage. Comparison of the actions of fostriecin and antisense-oligonucleotides specifically targeting human fostriecin-sensitive phosphatases revealed that the suppression PP4C alone is sufficient to mimic many actions of fostriecin. Importantly, antisense-oligonucleotides targeting PP4C induce apoptosis, with death occurring in tetraploid cells produced following mitotic slippage. This affect was not observed following the suppression of PP1C, PP2AC or PP5C. Although future studies are needed to clarify how the suppression of PP4C triggers mitotic slippage/apoptosis, our observations suggest further development of fostriecin class inhibitors should consider PP4C as a potentially important target. PMID:23671329

Theobald, Benjamin; Bonness, Kathy; Musiyenko, Alla; Andrews, Joel F.; Urban, Gudrun; Huang, Xizhong; Dean, Nicholas M.; Honkanen, Richard E.

2013-01-01

224

Working hard for recovery: mitotic kinases in the DNA damage checkpoint  

PubMed Central

Cell division in mitosis is tightly regulated via a group of protein kinases. Activation of these mitotic kinases is inhibited by the DNA damage checkpoint that arrests the cell cycle in interphase and prevents mitotic entry. Interestingly, it has been shown that the DNA damage checkpoint is feedback regulated by several mitotic kinases. These kinases are reactivated from checkpoint arrest to deactivate the checkpoint and restart cell cycle progression, thereby allowing the cell to recover from the DNA damage checkpoint. The emerging role of mitotic kinases in the DNA damage pathway provides important insights into cancer progression and treatment. PMID:23618492

2013-01-01

225

Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis  

PubMed Central

Mitotic homologous recombination promotes genome stability through the precise repair of DNA double-strand breaks and other lesions that are encountered during normal cellular metabolism and from exogenous insults. As a result, homologous recombination repair is essential during proliferative stages in development and during somatic cell renewal in adults to protect against cell death and mutagenic outcomes from DNA damage. Mutations in mammalian genes encoding homologous recombination proteins, including BRCA1, BRCA2 and PALB2, are associated with developmental abnormalities and tumorigenesis. Recent advances have provided a clearer understanding of the connections between these proteins and of the key steps of homologous recombination and DNA strand exchange. PMID:20177395

Moynahan, Mary Ellen; Jasin, Maria

2012-01-01

226

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

PubMed Central

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

1994-01-01

227

Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.  

PubMed Central

Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-inhibitory kinases that are required for preventing premature activation of the mitotic program. To identify Cdc2-inhibitory kinases in Drosophila, we screened for cDNA clones that rescue S. pombe wee1- mik1- mutants from lethal mitotic catastrophe. One of the genes identified in this screen, Drosophila wee1 (Dwee1), encodes a new Wee1 homologue. Dwee1 kinase is closely related to human and Xenopus Wee1 homologues, and can inhibit Cdc2 activity by phosphorylating a critical tyrosine residue. Dwee1 mRNA is maternally provided to embryos, and is zygotically expressed during the postblastoderm divisions of embryogenesis. Expression remains high in the proliferating cells of the central nervous system well after cells in the rest of the embryo have ceased dividing. The loss of zygotically expressed Dwee1 does not lead to mitotic catastrophe during postblastoderm cycles 14 to 16. This result may indicate that maternally provided Dwee1 is sufficient for regulating Cdc2 during embryogenesis, or it may reflect the presence of a redundant Cdc2 inhibitory kinase, as in fission yeast. Images PMID:8573790

Campbell, S D; Sprenger, F; Edgar, B A; O'Farrell, P H

1995-01-01

228

Endogenous localizome identifies 43 mitotic kinesins in a plant cell  

PubMed Central

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

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

2014-01-01

229

Endogenous localizome identifies 43 mitotic kinesins in a plant cell.  

PubMed

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

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

2014-03-18

230

Analysis and modeling of mitotic spindle orientations in three dimensions  

PubMed Central

The orientation of the mitotic spindle determines the relative size and position of the daughter cells and influences the asymmetric inheritance of localized cell fate determinants. The onset of mammalian neurogenesis, for example, coincides with changes in spindle orientation. To address the functional implications of this and related phenomena, precise methods for determining the orientation of the mitotic spindle in complex tissues are needed. Here, we present methodology for the analysis of spindle orientation in 3D. Our method allows statistical analysis and modeling of spindle orientation and involves two parameters for horizontal and vertical bias that can unambiguously describe the distribution of spindle orientations in an experimental sample. We find that 3D analysis leads to systematically different results from 2D analysis and, surprisingly, truly random spindle orientations do not result in equal numbers of horizontal and vertical orientations. We show that our method can describe the distribution of spindle orientation angles under different biological conditions. As an example of biological application we demonstrate that the adapter protein Inscuteable (mInsc) can actively promote vertical spindle orientation in apical progenitors during mouse neurogenesis. PMID:24381158

Juschke, Christoph; Xie, Yunli; Postiglione, Maria Pia; Knoblich, Juergen A.

2014-01-01

231

Bod1 regulates protein phosphatase 2A at mitotic kinetochores  

PubMed Central

Mitotic entry and progression require the activation of several mitotic kinases and the proper regulation and localization of several phosphatases. The activity and localization of each of these enzymes is tightly controlled through a series of specific activators, inhibitors and regulatory subunits. Two proteins, Ensa and Arpp-19, were recently identified as specific inhibitors of PP2A-B55 and are critical for allowing full activity of Cdk1/cyclin B and entry into mitosis. Here we show that Bod1, a protein required for proper chromosome alignment at mitosis, shares sequence similarity with Ensa and Arpp-19 and specifically inhibits the kinetochore-associated PP2A-B56 holoenzyme. PP2A-B56 regulates the stability of kinetochore-microtubule attachments by dephosphorylating several kinetochore proteins. Loss of Bod1 changes the balance of phosphorylation at kinetochores, causing defects in kinetochore function. Bod1, Ensa and Arpp-19 define a family of specific PP2A inhibitors that regulate specific PP2A holoenzymes at distinct locations and points in the cell cycle. PMID:24157919

Porter, Iain M.; Schleicher, Katharina; Porter, Michael; Swedlow, Jason R.

2013-01-01

232

A molecular mechanism of mitotic centrosome assembly in Drosophila  

PubMed Central

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

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

233

Callous-unemotional features, behavioral inhibition, and parenting: independent predictors of aggression in a high-risk preschool sample  

Microsoft Academic Search

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. Forty-nine preschoolers and their parents registering for Head Start programs were recruited for participation. Behavioral

Eva R. Kimonis; Paul J. Frick; Neil W. Boris; Anna T. Smyke; Amy H. Cornell; Jamie M. Farrell; Charles H. Zeanah

2006-01-01

234

A region-based high spatial resolution remotely sensed imagery classification algorithm based on multiscale fusion and feature weighting  

NASA Astrophysics Data System (ADS)

With the availability of high resolution multispectral imagery from sensors, it is possible to identify small-scale features in urban environment. Given attributes of image structure such as color, texture, have the character of highly scale dependency, a hierarchy segment fusion algorithm based on region deviation is proposed to extract more robust features and benefit single semantic level land cover classification. The fusion algorithm proposed is divided into in two successive sub-tasks: mean shift (MS) filtering based pre-segmentation and hierarchical segment optimization. Presegmentation is applied to get boundary- preserved and spectrally homogeneous initial regions, and then, a family of nested image partitions with ascending region areas is constructed by iteratively merging procedure. In every scale, regions of the corresponding critical size are evaluated according to potential region merge risk, which is measured by the region standard deviation change before and after a virtual merge. If a region measurement is larger than a specified change threshold, the region will be preserved to the next level and labeled as a candidate segment for following regionbased classification. Otherwise the segment will be merged to the next scale level. After fusing segments in different scales, a novel weighted minimum distance classifier is employed to get supervised classification result, in which every feature band's deviation is used to calculate its own weight. We show results for classification of a HR image over Washington DC Mall area taken by the HYDICE sensor. Different features combined with designed classifier have proved that fused segments provided a robust feature extraction and improve classification accuracy.

Wang, Leiguang; Mei, Tiancan; Qin, Qianqin

2009-10-01

235

High-order feature-based mixture models of classification learning predict individual learning curves and enable personalized teaching  

PubMed Central

Pattern classification learning tasks are commonly used to explore learning strategies in human subjects. The universal and individual traits of learning such tasks reflect our cognitive abilities and have been of interest both psychophysically and clinically. From a computational perspective, these tasks are hard, because the number of patterns and rules one could consider even in simple cases is exponentially large. Thus, when we learn to classify we must use simplifying assumptions and generalize. Studies of human behavior in probabilistic learning tasks have focused on rules in which pattern cues are independent, and also described individual behavior in terms of simple, single-cue, feature-based models. Here, we conducted psychophysical experiments in which people learned to classify binary sequences according to deterministic rules of different complexity, including high-order, multicue-dependent rules. We show that human performance on such tasks is very diverse, but that a class of reinforcement learning-like models that use a mixture of features captures individual learning behavior surprisingly well. These models reflect the important role of subjects’ priors, and their reliance on high-order features even when learning a low-order rule. Further, we show that these models predict future individual answers to a high degree of accuracy. We then use these models to build personally optimized teaching sessions and boost learning. PMID:23269833

Cohen, Yarden; Schneidman, Elad

2013-01-01

236

Speaker Verification Using Support Vector Machines and High-Level Features  

Microsoft Academic Search

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

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

2007-01-01

237

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

Microsoft Academic Search

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

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

2004-01-01

238

Small feature sizes and high aperture ratio organic light-emitting diodes by using laser-patterned polyimide shadow masks  

NASA Astrophysics Data System (ADS)

A shadow mask technique capable of realizing high resolution (>330 pixel-per-inch) and ˜100% aperture ratio Organic Light-Emitting Diode (OLED) full color displays is demonstrated. The technique utilizes polyimide contact shadow masks, patterned by laser ablation. Red, green, and blue OLEDs with very small feature sizes (<25 ?m) are fabricated side by side on one substrate. OLEDs fabricated via this technique have the same performance as those made by established technology. This technique has a strong potential to achieve high resolution OLED displays via standard vacuum deposition processes even on flexible substrates.

Kajiyama, Yoshitaka; Joseph, Kevin; Kajiyama, Koichi; Kudo, Shuji; Aziz, Hany

2014-02-01

239

Sub-population analysis based on temporal features of high content images  

E-print Network

Background: High content screening techniques are increasingly used to understand the regulation and progression of cell motility. The demand of new platforms, coupled with availability of terabytes of data has challenged ...

Rajapakse, Jagath

240

A Selective Overview of Variable Selection in High Dimensional Feature Space.  

PubMed

High dimensional statistical problems arise from diverse fields of scientific research and technological development. Variable selection plays a pivotal role in contemporary statistical learning and scientific discoveries. The traditional idea of best subset selection methods, which can be regarded as a specific form of penalized likelihood, is computationally too expensive for many modern statistical applications. Other forms of penalized likelihood methods have been successfully developed over the last decade to cope with high dimensionality. They have been widely applied for simultaneously selecting important variables and estimating their effects in high dimensional statistical inference. In this article, we present a brief account of the recent developments of theory, methods, and implementations for high dimensional variable selection. What limits of the dimensionality such methods can handle, what the role of penalty functions is, and what the statistical properties are rapidly drive the advances of the field. The properties of non-concave penalized likelihood and its roles in high dimensional statistical modeling are emphasized. We also review some recent advances in ultra-high dimensional variable selection, with emphasis on independence screening and two-scale methods. PMID:21572976

Fan, Jianqing; Lv, Jinchi

2010-01-01

241

A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization  

Microsoft Academic Search

Asymmetric cell division requires the orientation of mitotic spindles along the cell-polarity axis. In Drosophila neuroblasts, this involves the interaction of the proteins Inscuteable (Insc) and Partner of inscuteable (Pins). We report here that a human Pins-related protein, called LGN, is instead essential for the assembly and organization of the mitotic spindle. LGN is cytoplasmic in interphase cells, but associates

P. Todd Stukenberg; Ian G. Macara; Quansheng Du

2001-01-01

242

EFFECTS OF GIBBERELLIN, KINETIN, THIOUREA, AND PHOTOMORPHOGENIC RADIATION ON MITOTIC ACTIVITY IN DORMANT LETTUCE SEED  

Microsoft Academic Search

The effects of several germination-stimulating agents on mitotic ; activity in radicles of nongerminated lettuce seeds were studied using conditions ; near the upper limits of temperatures permitting germination. Under appropriate ; conditions where gibberellin, kinetin, thiourea, and red light could stimulate ; germination, only kinetin stimulated mitotic activity. Kinetin can be considered ; a true cell division factor in

A. H. Haber; H. J. Luippold

1960-01-01

243

MOVING MAGNETIC FEATURES AROUND AR 10930 FROM HIGH-RESOLUTION DATA OBSERVED BY HINODE/SOT  

SciTech Connect

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.

Li Xiaobo; Zhang Hongqi, E-mail: xiaobo_li_naoc@yahoo.com [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

2013-07-01

244

Diazonamide toxins reveal an unexpected function for ornithine ?-amino transferase in mitotic cell division  

PubMed Central

We have studied a naturally occurring small-molecule antimitotic called diazonamide A. Diazonamide A is highly effective at blocking spindle assembly in mammalian cell culture and does so through a unique mechanism. A biotinylated form of diazonamide A affinity purifies ornithine ?-amino transferase (OAT), a mitochondrial enzyme, from HeLa cell and Xenopus egg extracts. In the latter system, the interaction between diazonamide A and OAT is regulated by RanGTP. We find that specific OAT knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death, the effects largely phenocopying diazonamide A treatment in these cell lines. Our experiments reveal an unanticipated, paradoxical role for OAT in mitotic cell division and identify the protein as a target for chemotherapeutic drug development. PMID:17287350

Wang, Gelin; Shang, Libin; Burgett, Anthony W. G.; Harran, Patrick G.; Wang, Xiaodong

2007-01-01

245

Gene-specific factors determine mitotic expression and bookmarking via alternate regulatory elements  

PubMed Central

Transcriptional silencing during mitosis is caused by inactivation of critical transcriptional regulators and/or chromatin condensation. Inheritance of gene expression patterns through cell division involves various bookmarking mechanisms. In this report, we have examined the mitotic and post-mitotic expression of the DRA major histocompatibility class II (MHCII) gene in different cell types. During mitosis the constitutively MHCII-expressing B lymphoblastoid cells showed sustained occupancy of the proximal promoter by the cognate enhanceosome and general transcription factors. In contrast, although mitotic epithelial cells were depleted of these proteins irrespectively of their MHCII transcriptional activity, a distal enhancer selectively recruited the PP2A phosphatase via NFY and maintained chromatin accessibility. Based on our data, we propose a novel chromatin anti-condensation role for this element in mitotic bookmarking and timing of post-mitotic transcriptional reactivation. PMID:23303784

Arampatzi, Panagiota; Gialitakis, Manolis; Makatounakis, Takis; Papamatheakis, Joseph

2013-01-01

246

ETV6/RUNX1 abrogates mitotic checkpoint function and targets its key player MAD2L1  

PubMed Central

Approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia have an ETV6/RUNX1 (E/R) gene fusion that results from a t(12;21). This genetic subgroup of leukemia is associated with near-triploidy, near-tetraploidy, and trisomy 21 as rather specific types of secondary changes. Here, we show that, unlike various controls, E/R-expressing Ba/F3 clones acquire a tetraploid karyotype on prolonged culture, corroborating the assumption that E/R may attenuate the mitotic checkpoint (MC). Consistent with this notion, E/R-expressing diploid murine and human cell lines have decreased proportions of cells with 4N DNA content and a lower mitotic index when treated with spindle toxins. Moreover, both RUNX1 and E/R regulate mitotic arrest-deficient 2 L1 (MAD2L1), an essential MC component, by binding to promoter-inherent RUNX1 sites, which results in down-regulation of MAD2L1 mRNA and protein in E/R-expressing cells. Forced expression of E/R also abolishes RUNX1-induced reporter activation, whereas E/R with a mutant DNA-binding site leads to only minor effects. Our data link for the first time E/R, MC, and MAD2L1 and provide new insights into the function of the E/R fusion gene product. Although tetraploidy is an almost exclusive feature of E/R-positive leukemias, its rarity within this particular subgroup implies that further yet unknown factors are required for its manifestation. PMID:20190817

Krapf, G; Kaindl, U; Kilbey, A; Fuka, G; Inthal, A; Joas, R; Mann, G; Neil, JC; Haas, OA; Panzer-Grumayer, ER

2014-01-01

247

The Xenopus TACC homologue, maskin, functions in mitotic spindle assembly.  

PubMed

Maskin is the Xenopus homolog of the transforming acidic coiled coil (TACC)-family of microtubule and centrosome-interacting proteins. Members of this family share a approximately 200 amino acid coiled coil motif at their C-termini, but have only limited homology outside of this domain. In all species examined thus far, perturbations of TACC proteins lead to disruptions of cell cycle progression and/or embryonic lethality. In Drosophila, Caenorhabditis elegans, and humans, these disruptions have been attributed to mitotic spindle assembly defects, and the TACC proteins in these organisms are thought to function as structural components of the spindle. In contrast, cell division failure in early Xenopus embryo blastomeres has been attributed to a role of maskin in regulating the translation of, among others, cyclin B1 mRNA. In this study, we show that maskin, like other TACC proteins, plays a direct role in mitotic spindle assembly in Xenopus egg extracts and that this role is independent of cyclin B. Maskin immunodepletion and add-back experiments demonstrate that maskin, or a maskin-associated activity, is required for two distinct steps during spindle assembly in Xenopus egg extracts that can be distinguished by their response to "rescue" experiments. Defects in the "early" step, manifested by greatly reduced aster size during early time points in maskin-depleted extracts, can be rescued by readdition of purified full-length maskin. Moreover, defects in this step can also be rescued by addition of only the TACC-domain of maskin. In contrast, defects in the "late" step during spindle assembly, manifested by abnormal spindles at later time points, cannot be rescued by readdition of maskin. We show that maskin interacts with a number of proteins in egg extracts, including XMAP215, a known modulator of microtubule dynamics, and CPEB, a protein that is involved in translational regulation of important cell cycle regulators. Maskin depletion from egg extracts results in compromised microtubule asters and spindles and the mislocalization of XMAP215, but CPEB localization is unaffected. Together, these data suggest that in addition to its previously reported role as a translational regulator, maskin is also important for mitotic spindle assembly. PMID:15788567

O'Brien, Lori L; Albee, Alison J; Liu, Lingling; Tao, Wei; Dobrzyn, Pawel; Lizarraga, Sofia B; Wiese, Christiane

2005-06-01

248

Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder  

ERIC Educational Resources Information Center

Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

2014-01-01

249

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

Microsoft Academic Search

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

Peijun Li; Haiqing Xu; Jiancong Guo

2010-01-01

250

Investigation of Local Flow Features in Istanbul via High Resolution Atmospheric Simulations  

NASA Astrophysics Data System (ADS)

Three-dimensional non-hydrostatic meso-scale model, OMEGA (Operational Multi-scale Environment model with Grid Adaptivity), is utilized to investigate the thermally driven local flows and their interaction with each other in Istanbul. The city of Istanbul is located between two water bodies, Black Sea in the north and Sea of Marmara in the south. Two dates with still air and clear sky conditions, one in winter and the other in summer, are selected to determine the contribution of sea-land breezes and urban heat island circulation to the local flow over the city. The simulation results indicate that the model performance is reasonably well for both dates. In comparison with the atmospheric observations at the point where the rawinsonde measurements are taken in Istanbul, the root mean square errors in the simulated temperatures are usually found to be less than 2oC in both seasons. The simulations produce land and sea breeze circulations over the city in both winter and summer cases. Due to the sea-land-sea positioning of the city, two sea breezes form, one in the north (the Black Sea side) and the other in the south (the Marmara Sea side). Convergence takes place over the region as a result of the merge of the northerly and southerly sea breezes in both cases. The convergence occurs at about 15:00 p.m. in winter and about 11:00 a.m. in summer dates. Re-current circulations are observed above about 300 meters in the winter case and about 1000 meters in the summer case both in the west and east sides of the Bosphorus. Another important local flow feature is the channeling effect of the Bosphorus. Findings from the study further show that the urbanization in the southern coastal areas prevents much inland penetration of the southerly sea breeze. The large-scale wind direction also plays a significant role in the inland penetration of the sea breeze. Location of the sea breeze convergence differs in the simulations depending on the large-scale flow direction. KEYWORDS: sea-land breeze, urban heat circulation, channeling, meso-scale model, re-current flow.

Ezber, Y.; Boybeyi, Z.; Sen, O. L.; Karaca, M.

2012-04-01

251

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

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

1986-01-01

252

High-Resolution CT Features: Prognostic Significance in Peripheral Lung Adenocarcinoma with Bronchioloalveolar Carcinoma Components  

Microsoft Academic Search

Background: Based on Noguchi’s classification, adenocarcinomas with bronchioloalveolar carcinoma (BAC) components have a heterogeneous prognosis. However, until now, the prognostic factors in this tumor category have not been clarified. Objectives: We studied the prognostic significance of high-resolution CT (HRCT) findings in this tumor subtype. Materials and Methods: HRCT findings [lesion size, percentage of ground-glass opacity (GGO) areas in the lesion,

Shodayu Takashima; Yuichiro Maruyama; Minoru Hasegawa; Akitoshi Saito; Masayuki Haniuda; Masumi Kadoya

2003-01-01

253

Extraction of Features from High-resolution 3D LiDaR Point-cloud Data  

NASA Astrophysics Data System (ADS)

Airborne and tripod-based LiDaR scans are capable of producing new insight into geologic features by providing high-quality 3D measurements of the landscape. High-resolution LiDaR is a promising method for studying slip on faults, erosion, and other landscape-altering processes. LiDaR scans can produce up to several billion individual point returns associated with the reflection of a laser from natural and engineered surfaces; these point clouds are typically used to derive a high-resolution digital elevation model (DEM). Currently, there exist only few methods that can support the analysis of the data at full resolution and in the natural 3D perspective in which it was collected by working directly with the points. We are developing new algorithms for extracting features from LiDaR scans, and present method for determining the local curvature of a LiDaR data set, working directly with the individual point returns of a scan. Computing the curvature enables us to rapidly and automatically identify key features such as ridge-lines, stream beds, and edges of terraces. We fit polynomial surface patches via a moving least squares (MLS) approach to local point neighborhoods, determining curvature values for each point. The size of the local point neighborhood is defined by a user. Since both terrestrial and airborne LiDaR scans suffer from high noise, we apply additional pre- and post-processing smoothing steps to eliminate unwanted features. LiDaR data also captures objects like buildings and trees complicating greatly the task of extracting reliable curvature values. Hence, we use a stochastic approach to determine whether a point can be reliably used to estimate curvature or not. Additionally, we have developed a graph-based approach to establish connectivities among points that correspond to regions of high curvature. The result is an explicit description of ridge-lines, for example. We have applied our method to the raw point cloud data collected as part of the GeoEarthScope B-4 project on a section of the San Andreas Fault (Segment SA09). This section provides an excellent test site for our method as it exposes the fault clearly, contains few extraneous structures, and exhibits multiple dry stream-beds that have been off-set by motion on the fault.

Keller, P.; Kreylos, O.; Hamann, B.; Kellogg, L. H.; Cowgill, E. S.; Yikilmaz, M. B.; Hering-Bertram, M.; Hagen, H.

2008-12-01

254

Resurrecting remnants: The lives of post-mitotic midbodies  

PubMed Central

Around a century ago, the midbody was described as a structural assembly within the intercellular bridge during cytokinesis, which served to connect the two future daughter cells. The midbody has become the focus of intense investigation through the identification of a growing number of diverse cellular and molecular pathways that localize to the midbody and contribute to its cytokinetic functions ranging from selective vesicle trafficking, regulated microtubule, actin and ESCRT filament assembly and disassembly, and post-translational modification, such as ubiquitination. More recent studies revealed new and unexpected functions of midbodies that occur in post-mitotic cells. In this article, we provide a historical perspective, discuss exciting new roles for midbodies beyond their cytokinetic function and speculate on their potential contributions to pluripotency. PMID:23245592

Chen, Chun-Ting; Ettinger, Andreas W.; Huttner, Wieland B.; Doxsey, Stephen J.

2014-01-01

255

Mitotic Exit and Separation of Mother and Daughter Cells  

PubMed Central

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

Weiss, Eric L.

2012-01-01

256

A THERMODYNAMIC ANALYSIS OF MITOTIC SPINDLE EQUILIBRIUM AT ACTIVE METAPHASE  

PubMed Central

The mitotic apparatus of first-division metaphase eggs of the sea urchin Strongylocentrotus drobachiensis was observed by means of polarization microscopy under controlled temperature conditions. Eggs were fertilized and grown at two temperature extremes in order to produce two different sizes of available spindle pool. Slow division time allowed successive samples of such cells to be observed at the same point in metaphase but at different equilibrium temperatures, yielding curves of metaphase equilibrium birefringence vs. observational temperature. Using the plateau value of birefringence at higher temperatures as a measure of total available spindle pool and the observed birefringence at lower temperatures as a measure of polymerized material at equilibrium, the spindle protein association was evaluated according to the method of Inoué. Both pool conditions produced linear van't Hoff functions. Analysis of these functions yielded enthalpy and entropy changes of +55–65 kcal/mol and +197–233 entropy units (eu), respectively. These values for active mitotic metaphase are quite comparable to those obtained by Inoué and co-workers for arrested meiotic metaphase cells. When other equilibrium treatments were considered, the best fit to the experimental data was still that of Inoué, a treatment which theoretically involves first-order polymerization and dissociation kinetics. Treatment of metaphase cells with D2O by direct immersion drove the equilibrium to completion regardless of temperature, attaining or exceeding a birefringence value equal to the cell's characteristic pool size; perfusion with D2O appeared to erase the original temperature-determined pool size differences for the two growth conditions, attaining a maximum value characteristic of the larger pool condition. These data confirm Inoué's earlier contention that D2O treatment can modify the available spindle pool. PMID:4734864

Stephens, R. E.

1973-01-01

257

Effective multifractal features and l-variability diagrams of high-frequency price fluctuations time series  

E-print Network

In this manuscript we present a comprehensive study on the multifractal properties of high-frequency price fluctuations and instantaneous volatility of the equities that compose Dow Jones Industrial Average. The analysis consists about quantification of dependence and non-Gaussianity on the multifractal character of financial quantities. Our results point out an equivalent influence of dependence and non-Gaussianity on the multifractality of time series. Moreover, we analyse l-diagrams of price fluctuations. In the latter case, we show that the fractal dimension of these maps is basically independent of the lag between price fluctuations that we assume.

de Souza, Jeferson

2007-01-01

258

A small mission featuring an imaging x-ray polarimeter with high sensitivity  

NASA Astrophysics Data System (ADS)

We show that meaningful, highly sensitive x-ray polarimetry with imaging capability is possible with a small mission tailored to the NASA Explorer program. Such a mission—derived from the Imaging X-ray Polarimetry Explorer (IXPE) proposed to a previous NASA call—takes advantage of progress in light-weight x-ray optics and in gas pixel detectors to achieve sensitive time-resolved, spectrometric, imaging polarimetry. We outline the main characteristics and requirements of this mission and provide a realistic assessment of its scientific utility for modeling point-like and extended x-ray sources and for studying physical processes (including questions of fundamental physics).

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

2013-09-01

259

Some unique features of isentrophic flow of gas under high pressures  

NASA Astrophysics Data System (ADS)

A mathematical model of thermodynamic expansion is constructed for a real gas flowing under high pressure. The corresponding system of three Cauchy equations in virial form di - vdp = 0 bar-V/v = const vdp + bar-Vdbar-V (i - enthalpy, v - volume, p - pressure, bar-V - velocity, F - area of nozzle cross section) is reformulated with the total differentials di and dp expressed as functions of partial derivatives so that the process is redescribed by an equation for dT/dv (temperature-volume characteristic) and an equation for d bar-V/dv (velocity-volume characteristic). These equations are supplemented with the equation of state pv = zRT for a real gas (z expressed as a polynomial with empirical coefficients) and an equation for the specific heat at constant pressure C sub p = C sub v - v(T,v,z) (C sub v - specific heat at constant volume). This system of equations was solved numerically for determining the effects of intermolecular interaction forces and of departure from an ideal gas taking into account the distinct discharge and thrust characteristics of high-pressure nozzles.

Bebyakov, A. P.; Levin, V. Y.

1985-03-01

260

Experimental Investigation of Primary and Secondary Features in High-Mach-Number Shock-Bubble Interaction  

NASA Astrophysics Data System (ADS)

Experiments to study the compression and unstable evolution of an isolated soap-film bubble containing helium, subjected to a strong planar shock wave (M=2.95) in ambient nitrogen, have been performed in a vertical shock tube of square internal cross section using planar laser diagnostics. The early phase of the interaction process is dominated by the formation of a primary vortex ring due to the baroclinic source of vorticity deposited during the shock-bubble interaction, and the mass transfer from the body of the bubble to the vortex ring. The late time (long after shock interaction) study reveals the presence of a secondary baroclinic source of vorticity at high Mach number which is responsible for the formation of counterrotating secondary and tertiary vortex rings and the subsequent larger rate of elongation of the bubble.

Ranjan, Devesh; Niederhaus, John; Motl, Bradley; Anderson, Mark; Oakley, Jason; Bonazza, Riccardo

2007-01-01

261

Transmission electron microscopy specimen preparation perpendicular to the long axis of high aspect ratio features  

SciTech Connect

A new variation of transmission electron microscopy (TEM) specimen preparation is introduced. By thinning a tall high aspect ratio structure perpendicular to the long dimension (i.e., from the side) rather than from perpendicular to the short dimension (either the top or the bottom), it is possible to obtain a more uniformly thin TEM specimen over the entire long dimension of the structure. This article will describe the rational for this variation in specimen preparation. The necessary modifications of four different specimen preparation methods (in situ lift-out, traditional H-bar, ex situ lift-out, and tripod polishing) will be discussed and images of specimens obtained by both of these first two methods will be shown. Additional potential advantages and other applications of this specimen preparation method will be covered.

Irwin, R. B.; Anciso, A.; Jones, P. J.; Glenn, A. L.; Williams, B. L.; Sridhar, S.; Arshad, S. [TT-PEG PFA Laboratory, Texas Instruments, 13536 North Central Expressway, Mail Stop 947, Dallas, Texas 75243 (United States); MAKE Process Characterization Laboratory, Texas Instruments, 13121 TI Blvd., Mail Stop 347, Dallas, Texas 75243 (United States); Analog Technology Development, Texas Instruments, 13121 North Central Expressway, Mail Stop 364, Dallas, Texas 75243 (United States); DFAB Product Engineering, Texas Instruments, 13536 North Central Expressway, Mail Stop 947, Dallas, Texas 75243 (United States)

2009-11-15

262

Acinic cell carcinoma of minor salivary gland showing features of high-grade transformation  

PubMed Central

Introduction: Acinic cell carcinoma (AciCC) of salivary gland is a relatively infrequent tumor. Though known for its low-grade behavior, its unpredictable element of recurrence and malignancy should never be ignored. Case Report: A male patient with complaints of pain and swelling in the left jaw region since a year was operated based on the computed tomography (CT) and incisional biopsy report. Histopathology (routine staining, special staining, immunostaining and electron microscopy) of the excised specimen revealed it to be a variant of AciCC from minor salivary gland. Discussion: To the best of our knowledge, this is the first case of AciCC showing propensity for high-grade transformation (HGT), arising from minor salivary gland, being reported. The rarity of such variants and the importance of various investigative techniques in the diagnosis of such cases are discussed. PMID:24959046

Ilayaraja, Vadivel; Prasad, H; Anuthama, Krishnamurthy; Sruthi, Ranganath

2014-01-01

263

Centrifugation aided highly sensitive detection of nitrite with a dye-silica conjugate featuring cleavable linkages.  

PubMed

Rhodamine-silica nanocomposite bridged by a cleavable linker was used for highly sensitive nitrite detection via analyte triggered release of rhodamine from silica particles. Centrifugal removal of pristine nanoconjugate from the assay medium effectively decreased background signals in the supernatant whereas rhodamine unleashed from silica platform is retained in the supernatant, enabling facile detection of nitrite with an assay limit of 50nM which is 400 folds lower than legislated maximum contaminant levels of nitrite in drinking water. Assays based on small molecular chemosensors are often compromised by their intrinsic fluorescence signals and low aqueous compatibility. The performance of water compatible rhodamine-silica nanocomposite suggests broad analytical potentials of centrifugal nanoparticulate systems with dyes conjugated via appropriate cleavable linkers. PMID:25227716

Xu, Hehuan; Xue, Zhongwei; Han, Jiahuai; Su, Xinhui; Han, Shoufa

2014-10-15

264

DE/ISIS conjunction comparisons of high-latitude electron density features  

NASA Technical Reports Server (NTRS)

This paper presents a comparison between the ISIS-1 and -2 topside sounder measurements of electron number density, N(e), with the in situ ion and N(e) measurements by the Langmuir probe aboard the Dynamics Explorer 2 (DE 2) during four high-latitude ISIS/DE magnetic field-aligned conjunctions. The ISIS-derived N(e) values, even at the greatest distance from the sounder, were found to agree with the Langmuir probe measurements to within about 30 percent over a density range of more than two decades on three of the four comparisons; the fourth comparison which included data with strong N(e) irregularities, showed a difference of 60 percent.

Hoegy, Walter R.; Benson, Robert F.

1988-01-01

265

Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus  

PubMed Central

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.

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

266

The Structure, Water Budget, and Radiational Features of a High-Latitude Warm Front.  

NASA Astrophysics Data System (ADS)

On 30 September 1994 an Arctic low pressure system passed over the southern Beaufort Sea area of northern Canada and research aircraft observations were made within and around the warm front of the storm. This study is unique in that the warm front contained subzero centigrade temperatures across the entire frontal region. The overall structure of the warm front and surrounding region was similar to midlatitude storms; however, the precipitation rates, liquid water content magnitudes, horizontal and vertical winds, vertical wind shear, turbulence, and thermal advection were very weak. In addition, a low-level jet and cloud bands were aligned parallel to the warm front, near-neutral stability occurred within and around the front, and conditional symmetric instability was likely occurring. A steep frontal region resulted from strong Coriolis influences that in turn limited the amount of cloud and precipitation ahead of the system. The precipitation efficiency of the storm was high (60%) but is believed to be highly dependent on the stage of development. The mesoscale frontogenetic forcing was primarily controlled by the tilting of isentropic surfaces with confluence/convergence being the secondary influence. Sublimation contributions may have been large in the earlier stages of storm development. Satellite and aircraft radiometers underestimated cloud top heights by as much as 4 km and this was mostly due to the near transparency of the lofted ice layer in the upper portion of the storm. Maximum surface solar radiation deficits ranged between 91 W m2 and 187 W m2 at two surface observing sites. This common type of cloud system must have a major impact on the water and energy cycles of northern Canada in the autumn and therefore must be well accounted for within climate models.

Hanesiak, John M.; Stewart, Ronald E.; Szeto, Kit K.; Hudak, David R.; Leighton, Henry G.

1997-06-01

267

Features of highly structured equatorial plasma irregularities deduced from CHAMP observations  

NASA Astrophysics Data System (ADS)

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.

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

2012-08-01

268

The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint  

PubMed Central

M-phase checkpoints inhibit cell division when mitotic spindle function is perturbed. Here we show that the Saccharomyces cerevisiae MPS1 gene product, an essential protein kinase required for spindle pole body (SPB) duplication (Winey et al., 1991; Lauze et al., 1995), is also required for M-phase check-point function. In cdc31-2 and mps2-1 mutants, conditional failure of SPB duplication results in cell cycle arrest with high p34CDC28 kinase activity that depends on the presence of the wild-type MAD1 checkpoint gene, consistent with checkpoint arrest of mitosis. In contrast, mps1 mutant cells fail to duplicate their SPBs and do not arrest division at 37 degrees C, exhibiting a normal cycle of p34CDC28 kinase activity despite the presence of a monopolar spindle. Double mutant cdc31-2, mps1-1 cells also fail to arrest mitosis at 37 degrees C, despite having SPB structures similar to cdc31-2 single mutants as determined by EM analysis. Arrest of mitosis upon microtubule depolymerization by nocodazole is also conditionally absent in mps1 strains. This is observed in mps1 cells synchronized in S phase with hydroxyurea before exposure to nocodazole, indicating that failure of checkpoint function in mps1 cells is independent of SPB duplication failure. In contrast, hydroxyurea arrest and a number of other cdc mutant arrest phenotypes are unaffected by mps1 alleles. We propose that the essential MPS1 protein kinase functions both in SPB duplication and in a mitotic checkpoint monitoring spindle integrity. PMID:8567717

1996-01-01

269

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

PubMed Central

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

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

2013-01-01

270

Quark pair production in high energy pA collisions: General features  

E-print Network

A consistent treatment of both multiple scattering and small x quantum evolution effects on pair production in high energy pA collisions is feasible in the framework of the Color Glass Condensate (hep-ph/0402257). We first discuss the properties of quark pair production in the classical effective theory where only multiple scattering effects are included. Explicit results are given for pair production as a function of the invariant mass of pairs, the pair momenta, the atomic mass number A and the quark mass. We relate the logarithms that appear in our formulation of pair production to logarithms that appear in the limit of collinear factorization in QCD. Violations of kT factorization and medium modifications, as represented by the Cronin effect, are also investigated. We next consider how small x quantum evolution (shadowing) effects modify the results for pair production. In particular, we provide results for the rapidity distribution of pairs and the dependence of the Cronin effect on rapidity. We discuss the dependence of our results on the initial conditions for small x evolution and comment on its implications for pair production at RHIC and the LHC.

Hirotsugu Fujii; Francois Gelis; Raju Venugopalan

2006-03-14

271

Features charge states of heavy energetic particles for high number of events.  

NASA Astrophysics Data System (ADS)

The solar energetic particle (SEP) C, O and Fe ion charge states in 51 gradual events of solar cycle 23 were determined using an original method based on a modified form of the particle energy spectra, consisting of two power law spectra separated by a knee. The experimental data from the GOES satellites (protons) as well as from the ULEIS (all particles) and SIS instruments aboard the ACE satellite (ions He, C, O and Fe) were used to calculate the average charge states of C ions (5.88 ± 0.06; with standard deviation of the experimental data ?total=0.35), O ions (6.80 ± 0.07; ?total = 0.59) and Fe ions (14.44 ± 0.25; ?total = 1.61). We found that the charge states of high-energy heavy ions of the Sun do not depend on the size (capacity) of SEP events, on the particle energy (in the interval 0.3-30 MeV / nucleon), or on the variation of the relative composition of heavy ion fluxes.

Nymmik, Rikho

272

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

E-print Network

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...

Khusnutdinoff, Ramil M

2011-01-01

273

Cdk1 Inactivation Terminates Mitotic Checkpoint Surveillance and Stabilizes Kinetochore Attachments in Anaphase  

PubMed Central

Summary Two mechanisms safeguard the bipolar attachment of chromosomes in mitosis. A correction mechanism destabilizes erroneous attachments that do not generate tension across sister kinetochores [1]. In response to unattached kinetochores, the mitotic checkpoint delays anaphase onset by inhibiting the anaphase-promoting complex/cyclosome (APC/CCdc20) [2]. Upon satisfaction of both pathways, the APC/CCdc20 elicits the degradation of securin and cyclin B [3]. This liberates separase triggering sister chromatid disjunction and inactivates cyclin-dependent kinase 1 (Cdk1) causing mitotic exit. How eukaryotic cells avoid the engagement of attachment monitoring mechanisms when sister chromatids split and tension is lost at anaphase is poorly understood [4]. Here we show that Cdk1 inactivation disables mitotic checkpoint surveillance at anaphase onset in human cells. Preventing cyclin B1 proteolysis at the time of sister chromatid disjunction destabilizes kinetochore-microtubule attachments and triggers the engagement of the mitotic checkpoint. As a consequence, mitotic checkpoint proteins accumulate at anaphase kinetochores, the APC/CCdc20 is inhibited, and securin reaccumulates. Conversely, acute pharmacological inhibition of Cdk1 abrogates the engagement and maintenance of the mitotic checkpoint upon microtubule depolymerization. We propose that the simultaneous destruction of securin and cyclin B elicited by the APC/CCdc20 couples chromosome segregation to the dissolution of attachment monitoring mechanisms during mitotic exit. PMID:24583019

Vazquez-Novelle, Maria Dolores; Sansregret, Laurent; Dick, Amalie E.; Smith, Christopher A.; McAinsh, Andrew D.; Gerlich, Daniel W.; Petronczki, Mark

2014-01-01

274

High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients with Primary Immunodeficiencies  

PubMed Central

To estimate the susceptibility to enterovirus infection and the frequency of long-term poliovirus excreters in Tunisian patients with primary immunodeficiencies (PIDs), enteroviruses were assessed in stool specimens of 82 patients with humoral, combined, and other PIDs. Isolated viruses were typed and intratyped by standard molecular techniques, and the whole VP1 region of poliovirus isolates was sequenced. Polioviruses were detected in 6 patients; all isolates were vaccine related. Five patients rapidly stopped excretion; one excreted a poliovirus type 1 isolate for several months, and the isolate accumulated up to 14 mutations in the VP1 region. Nonpolio enteroviruses were identified in 6 patients; 4 of them kept excreting the same strain for more than 6 months. The rate of enterovirus infection was 13.4% of the PID patients and 20.7% of those with an IgG defect; it greatly exceeded the rates generally found in Tunisian supposed-immunocompetent individuals (4.1% during the study period; P = 0.001 and P < 0.0001, respectively). Interestingly, patients with combined immunodeficiencies were at a higher risk for enterovirus infection than those with an exclusively B cell defect. A major histocompatibility complex (MHC) class II antigen expression defect was found in 54% of enterovirus-positive patients and in the unique long-term poliovirus excreter. The study results also suggest that substitutive immunoglobulin therapy may help clearance of a poliovirus infection and that most PID patients have the ability to stop poliovirus excretion within a limited period. However, the high susceptibility of these patients to enterovirus infection reinforces the need for enhanced surveillance of these patients until the use of oral poliovirus vaccine (OPV) is stopped. PMID:22914367

Driss, Nadia; Ben-Mustapha, Imen; Mellouli, Fethi; Ben Yahia, Ahlem; Touzi, Henda; Bejaoui, Mohamed; Ben Ghorbel, Mohamed; Barbouche, Mohamed-Ridha

2012-01-01

275

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

NASA Astrophysics Data System (ADS)

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.

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

2011-12-01

276

Atmospheric-water absorption features near 2.2 micrometers and their importance in high spectral resolution remote sensing  

NASA Technical Reports Server (NTRS)

Selective absorption of electromagnetic radiation by atmospheric gases and water vapor is an accepted fact in terrestrial remote sensing. Until recently, only a general knowledge of atmospheric effects was required for analysis of remote sensing data; however, with the advent of high spectral resolution imaging devices, detailed knowledge of atmospheric absorption bands has become increasingly important for accurate analysis. Detailed study of high spectral resolution aircraft data at the U.S. Geological Survey has disclosed narrow absorption features centered at approximately 2.17 and 2.20 micrometers not caused by surface mineralogy. Published atmospheric transmission spectra and atmospheric spectra derived using the LOWTRAN-5 computer model indicate that these absorption features are probably water vapor. Spectral modeling indicates that the effects of atmospheric absorption in this region are most pronounced in spectrally flat materials with only weak absorption bands. Without correction and detailed knowledge of the atmospheric effects, accurate mapping of surface mineralogy (particularly at low mineral concentrations) is not possible.

Kruse, F. A.; Clark, R. N.

1986-01-01

277

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

SciTech Connect

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.

Olson, H.G.; Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

1981-10-01

278

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

SciTech Connect

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.

Olson, H.G. (Univ. of California, Irvine); Lyons, K.P.; Aronow, W.S.; Stinson, P.J.; Kuperus, J.; Waters, H.J.

1981-10-01

279

Distinctive features of collisionless gradient drift instabilities in a high-? plasma in a highly nonuniform magnetic field  

NASA Astrophysics Data System (ADS)

A set of Vlasov-Maxwell equations for collisionless electromagnetic drift instabilities of high-? plasma configurations with a nonuniform magnetic fields is solved. The effect of the transverse static magnetic field variation and magnetic field line curvature, as well as the plasma temperature and density gradients, is considered. It is shown that, in a nonuniform magnetic field, the behavior of the instabilities differs substantially from that in a uniform field. Electromagnetic modes propagating strictly transverse to the lines of the static magnetic field are analyzed in detail, and unstable solutions are obtained for both extraordinary and ordinary waves. Numerical results show that, in the latter case, instability occurs when the magnetic field decreases toward the periphery and the plasma temperature and density gradients are oppositely directed.

Chirkov, A. Yu.; Khvesyuk, V. I.

2011-05-01

280

Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo  

E-print Network

, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish....pone.0000979.g004 Ewsr1 in Mitosis PLoS ONE | www.plosone.org 4 October 2007 | Issue 10 | e979 Loss of mitotic integrity accompanied by mislocalization of Aurora B proteins in EWSR1 deficient Hela cells The Ewsr1 knockdown in zebrafish embryos induced mitotic...

Azuma, Mizuki; Embree, Lisa J.; Sabaawy, Hatem; Hickstein, Dennis D.

2007-10-03

281

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

PubMed

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

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

2012-06-01

282

Microscale Analysis of Surface Wind Variability by Resolving Small-Scale Terrain Features in High-Resolution Simulations  

NASA Astrophysics Data System (ADS)

The temporal and spatial variability of surface winds is a critical information in predicting the transport of atmospheric tracers and pollutants, operating wind energy power plants, and evaluating atmospheric environment in urban areas where deteriorating factors such as heat island phenomenta are significant. These surface wind analyses are required especially in areas with complex terrain and land-use characteristics. Although general meterological conditons can be evaluated by the current regional-scale simulations with a grid spacing of O(1 km) to O(10 km), the evaluation of surface winds that are sensitively affected by small-scale features of terrain and land use is relatively poor. In this study, we investigate the temporal and spatial variability of surface winds in the microscale by conducting high-resolution simulations with small-scale terrain features being well-resolved. A mesoscale meteorological model MM5 is used for the simulations in multi-nested mesoscale domains with a minimum grid spacing of 111 m in the finest-mesh domain. The area of interest is a Japanese peninsula whose size is about 30 km by 10 km projecting into the Pacific Ocean. A variety of simulations are conducted for a one-year period and the six-months periods of summer (JJA) and winter (DJF). In coarse-mesh (i.e., 1 km) runs examining the effects of boundary-layer mixing parameterizations, the sensitivity to stability is examined in different seasons and in different meteorological settings. With a best choice of the parameterization, 111-m mesh simulations are conducted and compared with the coarse-mesh results. Small-scale and short-term variabilities of surface winds are reproduced with the fine-mesh simulations. As the spatial variability of terrain elevations increases, the variability of wind speeds increases especially under weak-wind conditions. Resolving representative scales of terrain is important in predicting microscale features of surface winds.

Takemi, T.; Hatamura, S.

2007-12-01

283

Epidemiological features of hepatitis B and C infection in a high risk population: results of screening programs  

PubMed Central

Aim The aim of this study was to report the epidemiological features of HBV & HCV infection in an Iranian high risk population. Background Hepatitis B and hepatitis C infections are worldwide serious public health problems. Iran has an intermediate prevalence of infection and a screening program was started in 2010 among high risk individuals. Patients and methods This cross-sectional study was conducted on 4455 new patients during two past years. Demographic information, age, gender, occupational status, medical history, history of vaccination against HBV, high risk exposure and laboratory findings were collected for each patient. Then distribution of demographic and risk factors was evaluated in each type of hepatitis. Results The mean age of patients was 45.6±17.3 years. More than two-thirds of the diagnosed cases were infected with HBV. 74% of patients were carriers of hepatitis virus. 60% of patients had no symptoms at diagnosis. Illicit intravenous drug use was most common high risk exposure in patients under study (n=366, 8.2%). High risk behaviors including illicit intravenous drug use and unprotected sex were relatively higher in patients infected with hepatitis C compared to patients with hepatitis B infection. Conclusion Findings of this study suggest that illicit intravenous drug use, contact with an infected household member and unprotected sex are the most common high risk exposure in Iranian patients infected with viral hepatitis. Therefore, preventive strategies such as health education, vaccination and screening programs should be directed to these groups. The results also show that a majority of patients have no symptoms at the time of diagnosis, therefore periodic screening tests in high risk groups is required. PMID:24834260

Noori, Simin; Gol-Mohamadi, Ali; Sarbazi, Mohammad Reza; Farsar, Ahmad Reza

2013-01-01

284

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

SciTech Connect

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.

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

285

Industrial applications demanding low and high resolution features realized by soft UV-NIL and hot embossing  

NASA Astrophysics Data System (ADS)

There are several applications either currently in production or in late stage R&D, for UV-based Nanoimprint Lithography (UV-NIL) and Hot Embossing (HE) that require a full-field imprint technology in order to make these processes either feasible or costeffective. These applications cover a wide range of features sizes from the millimeter range down to sub-100 nm. Because of the total thickness variation (TTV) associated with the imprinted substrates, full-field imprinting requires fabrication of a "soft" or "working" stamp from a "hard" stamp usually made from materials such as nickel, quartz or silicon. Several materials and processes have previously been identified that allow for full-field imprinting, however, these materials all have drawbacks associated with them that hinder their movement into High Volume Manufacturing (HVM) environments. EV Group Inc (EVG) has, in cooperation with our NILCOMTM partners, identified a novel set of polymeric materials and stamp fabrication processes that allow for full-field imprinting solutions suitable for these HVM environments. These materials have proven effective for imprinting at both millimeter feature sizes all the way down to 50 nm - full field. These materials, and the processes associated with their fabrication into working/soft stamps, should allow for a superior cost-of-ownership benefit and facilitate the movement of imprint lithography into industrial applications.

Miller, R.; Glinsner, T.; Kreindl, G.; Lindner, P.; Wimplinger, M.

2009-03-01

286

High resolution transmission electron microscope Imaging and first-principles simulations of atomic-scale features in graphene membrane  

NASA Astrophysics Data System (ADS)

Ultra-thin membranes such as graphene[1] are of great importance for basic science and technology applications. Graphene sets the ultimate limit of thinness, demonstrating that a free-standing single atomic layer not only exists but can be extremely stable and strong [2--4]. However, both theory [5, 6] and experiments [3, 7] suggest that the existence of graphene relies on intrinsic ripples that suppress the long-wavelength thermal fluctuations which otherwise spontaneously destroy long range order in a two dimensional system. Here we show direct imaging of the atomic features in graphene including the ripples resolved using monochromatic aberration-corrected transmission electron microscopy (TEM). We compare the images observed in TEM with simulated images based on an accurate first-principles total potential. We show that these atomic scale features can be mapped through accurate first-principles simulations into high resolution TEM contrast. [1] Geim, A. K. & Novoselov, K. S. Nat. Mater. 6, 183-191, (2007). [2] Novoselov, K. S.et al. Science 306, 666-669, (2004). [3] Meyer, J. C. et al. Nature 446, 60-63, (2007). [4] Lee, C., Wei, X. D., Kysar, J. W. & Hone, J. Science 321, 385-388, (2008). [5] Nelson, D. R. & Peliti, L. J Phys-Paris 48, 1085-1092, (1987). [6] Fasolino, A., Los, J. H. & Katsnelson, M. I. Nat. Mater. 6, 858-861, (2007). [7] Meyer, J. C. et al. Solid State Commun. 143, 101-109, (2007).

Wang, Wei; Bhandari, Sagar; Yi, Wei; Bell, David; Westervelt, Robert; Kaxiras, Efthimios

2012-02-01

287

Spectral features of Mini-Neptunes and EGP orbiting different stars: exploring the effect of high stellar FUV radiation  

NASA Astrophysics Data System (ADS)

Motivated by the growing population of hot exoplanets, we calculated an atmospheric grid for hot mini-Neptune and giant planets, that links astrophysical observable parameters - orbital distance and stellar type - with the atmospheric features expected in transmission and emission spectra. We link a 1D code that calculates the atmospheric thermal structure with a photochemical model that includes disequilibrium chemistry for planets with temperature between 2700K and 700K and explore the effect of empirical model parameters like eddy diffusion coefficients on the results (Miguel & Kaltenegger, 2013). We then use a line by line radiative transfer code to generate the observable spectra. Our models explore the detectable atmospheric features for a wide range of stellar types from F to M for distances between 0.01AU and 0.1 AU. Many main sequence M stars present strong chromospheric activity that produces high-energy radiation. That strongly affects hot exoplanet atmospheres. We use our models to reproduce results for known planets (WASP-12b, CoRoT-2b, XO-1b and HD189733b), model a new planet (HD97658b) and produce a grid for observed planets as well as to inform future observations. Our grid can be applied to current and future observations to characterize exoplanet atmospheres and serves as a reference to interpret atmospheric retrieval analysis results.

Miguel, Y.; Kaltenegger, L.

2014-03-01

288

Volcanic Features  

NSDL National Science Digital Library

This interactive resource adapted from the National Park Service illustrates the variety of landforms and features created by volcanoes. Featured are calderas, craters, fumaroles and other geothermal features, igneous rocks, lava flows, lava tubes, and maars.

Foundation, Wgbh E.

2005-12-17

289

Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold  

E-print Network

Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold) chromosomes were studied by using micromechanical force measurement during nu- clease digestion. Micrococcal response of, and then to go on to completely disintegrate, single metaphase newt chromosomes

Poirier, Michael

290

Regulation and functions of Cdc14 in mitotic exit in Saccharomyces cerevisiae  

E-print Network

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 ...

Tomson, Brett N

2009-01-01

291

Inhibition of a Mitotic Motor Protein: Where, How, and Conformational Consequences  

SciTech Connect

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.

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

292

Modulation of mitotic progression and cell cycle checkpoints by phosphorylation-dependent protein-protein interactions  

E-print Network

Alteration of mitotic gene function has recently been discovered to play a key role in tumor formation and cancer progression through the induction of chromosomal aberrations and genomic instability. Polo-like-kinase-1 is ...

Lowery, Drew M

2007-01-01

293

Does delay in fixation affect the number of mitotic figures in processed tissue?  

PubMed Central

The effect of delay in fixation on the number of mitotic figures in tissues has received little attention, and previous studies have reached differing conclusions. The numbers of mitotic figures in the normal mucosa of six colectomy specimens were counted with delays in fixation of 30 minutes, one hour, two hours, three hours and six hours for samples from each specimen. The numbers of mitotic figures were counted in 50 whole crypts in each specimen by two observers. All phases of mitosis were counted. The number of observable mitotic figures declined by about 30% with a delay in fixation of two hours and by 50% with a delay of six hours. This observation has important implications for the handling of surgical specimens. PMID:2199539

Cross, S S; Start, R D; Smith, J H

1990-01-01

294

Spatial and temporal coordination of genome segregation with activation of the Mitotic Exit Network  

E-print Network

In budding yeast, an essential Hippo-like signal transduction cascade known as the Mitotic Exit Network (MEN) governs the final cell cycle transition, the mitosis to G1 transition. To ensure the accurate execution of ...

Rock, Jeremy M. (Jeremy Michael)

2012-01-01

295

Rhn1, a nuclear protein, is required for suppression of meiotic mRNAs in mitotically dividing fission yeast.  

PubMed

In the fission yeast Schizosaccharomyces pombe, many meiotic mRNAs are transcribed during mitosis and meiosis and selectively eliminated in mitotic cells. However, this pathway for mRNA decay, called the determinant of selective removal (DSR)-Mmi1 system, targets only some of the numerous meiotic mRNAs that are transcribed in mitotic cells. Here we describe Rhn1, a nuclear protein involved in meiotic mRNA suppression in vegetative fission yeast. Rhn1 is homologous to budding yeast Rtt103 and localizes to one or a few discrete nuclear dots in growing vegetative cells. Rhn1 colocalizes with a pre-mRNA 3'-end processing factor, Pcf11, and with the 5'-3' exoribonuclease, Dhp1; moreover, Rhn1 coimmunoprecipitates with Pcf11. Loss of rhn1 results in elevated sensitivity to high temperature, to thiabendazole (TBZ), and to UV. Interestingly, meiotic mRNAs--including moa1(+), mcp5(+), and mug96(+)--accumulate in mitotic rhn1? cells. Accumulation of meiotic mRNAs also occurs in strains lacking Lsk1, a kinase that phosphorylates serine 2 (Ser-2) in the C-terminal domain (CTD) of RNA polymerase II (Pol II), and in strains lacking Sen1, an ATP-dependent 5'-3' RNA/DNA helicase: notably, both Lsk1 and Sen1 have been implicated in termination of Pol II-dependent transcription. Furthermore, RNAi knockdown of cids-2, a Caenorhabditis elegans ortholog of rhn1(+), leads to elevated expression of a germline-specific gene, pgl-1, in somatic cells. These results indicate that Rhn1 contributes to the suppression of meiotic mRNAs in vegetative fission yeast and that the mechanism by which Rhn1 downregulates germline-specific transcripts may be conserved in unicellular and multicellular organisms. PMID:22912768

Sugiyama, Tomoyasu; Sugioka-Sugiyama, Rie; Hada, Kazumasa; Niwa, Ryusuke

2012-01-01

296

High-fat diet-induced changes in liver thioredoxin and thioredoxin reductase as a novel feature of insulin resistance  

PubMed Central

High-fat diet (HFD) can induce oxidative stress. Thioredoxin (Trx) and thioredoxin reductase (TrxR) are critical antioxidant proteins but how they are affected by HFD remains unclear. Using HFD-induced insulin-resistant mouse model, we show here that liver Trx and TrxR are significantly decreased, but, remarkably, the degree of their S-acylation is increased after consuming HFD. These HFD-induced changes in Trx/TrxR may reflect abnormalities of lipid metabolism and insulin signaling transduction. HFD-driven accumulation of 4-hydroxynonenal is another potential mechanism behind inactivation and decreased expression of Trx/TrxR. Thus, we propose HFD-induced impairment of liver Trx/TrxR as major contributor to oxidative stress and as a novel feature of insulin resistance.

Qin, Huijun; Zhang, Xiaolin; Ye, Fei; Zhong, Liangwei

2014-01-01

297

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

PubMed

The anterior pituitary is active mitotically and apoptotically under basal conditions and in response to a variety of physiological and pathophysiological stimuli. Hypothyroidism 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 pituitary following surgical thyroidectomy and subsequent thyroid hormone treatment and withdrawal using an extremely accurate system for quantifying directly identified mitotic and apoptotic events. Despite the expected increase in the number and/or proportion of immunohistochemically identifiable thyrotrophs three weeks after thyroidectomy, mitotic and apoptotic activity remained unchanged, as did pituitary wet weight, in comparison with sham-operated and intact controls. In contrast, mitotic but not apoptotic activity was enhanced by treatment of thyroidectomized animals with thyroid hormones (triiodothyronine (T3) and thyroxine (T4) 1.8 microg and 3.6 microg/100 g body weight per day respectively), and once again declined to levels seen in intact animals within 72 h of subsequent thyroid hormone withdrawal. Thyroid hormone-induced enhancement of mitotic activity was also seen in intact rats treated with similar doses of thyroid hormones for 7 days and in thyroidectomized rats treated for a similar period with very low dose thyroid hormone replacement at a level that had no effect on raised hypothalamic TRH- or pituitary TSHbeta-transcript prevalence (0.018 microg T3 plus 0.036 microg T4/100 g body weight per day). Thus changes in mitotic and apoptotic activity are unlikely to be the principle mechanism for the apparent increase in thyrotrophs up to 4 weeks after thyroidectomy. In contrast, the data indicate that thyroid hormones have a permissive effect on anterior pituitary mitotic activity in thyroidectomized male rats. Thyroid hormone-induced enhancement of mitotic activity in intact rats further suggests that in euthyroid rats, ambient thyroid hormone levels are a limiting factor for anterior pituitary mitotic activity. In summary, this time course study of young, male rats has shown for the first time that thyroidectomy, thyroid hormone replacement and subsequent withdrawal has no significant effect on anterior pituitary apoptotic activity. Secondly, it has shown that the anterior pituitary mitotic response to thyroidectomy is blocked by complete thyroid hormone deprivation, but can be restored by very low level thyroid hormone replacement, and thirdly that in intact animals thyroid hormone levels significantly limit anterior pituitary mitotic activity. PMID:14709142

Nolan, L A; Thomas, C K; Levy, A

2004-01-01

298

A dynamic, mitotic-like mechanism for bacterial chromosome segregation  

PubMed Central

The mechanisms that mediate chromosome segregation in bacteria are poorly understood. Despite evidence of dynamic movement of chromosome regions, to date, mitotic-like mechanisms that act on the bacterial chromosome have not been demonstrated. Here we provide evidence that the Vibrio cholerae ParAI and ParBI proteins are components of an apparatus that pulls the origin region of the large V. cholerae chromosome to the cell pole and anchors it there. ParBI interacts with a conserved origin-proximal, centromere-like site (parSI) that, following chromosome replication, segregates asymmetrically from one pole to the other. While segregating, parSI stretches far away from neighboring chromosomal loci. ParAI forms a dynamic band that extends from the pole to the segregating ParBI/parSI complex. Movement of ParBI/parSI across the cell occurs in concert with ParAI retraction. Deletion of parAI disrupts proper origin localization and segregation dynamics, and parSI no longer separates from nearby regions. These data suggest that ParAI forms a dynamic structure that pulls the ParBI-bound chromosome to the pole in a process analogous to anaphase of eukaryotic mitosis. PMID:17158745

Fogel, Michael A.; Waldor, Matthew K.

2006-01-01

299

A 3-D Biophysical Model of Mitotic Spindle Formation  

NASA Astrophysics Data System (ADS)

The mitotic spindle is the scaffolding on which plant and animal cell division occurs. It is known that under certain circumstances the spindle self-assembles, using only a few functional elements. We have been developing increasingly realistic biophysical models of spindle self-assembly. Our earlier 2-D model produced spindle patterns under certain conditions. Our more realistic 3-D model is defined by coupled Langevin equations that mimic the mechanical and thermal interactions between microtubules and molecular motors. Microtubules pivot on fixed kinesin motors and are drawn into poles by dynein motors. The distribution of pivot points form boundary conditions whose spherical asymmetry guides spindle formation. Unlike the 2-D model, the 3-D model correctly handles microtubule entanglement. Initial runs of the 3-D model show that spindle self-assembly is indeed possible under certain conditions. We are currently performing calculations to determine how parameter changes affect spindle formation and pattern morphology. In particular, we are varying dynein motor processivity, the degree of spherical asymmetry, and dynein motor concentrations.

Schaffner, Stuart

2005-03-01

300

Effects of polyamines and polyamine biosynthetic inhibitors on mitotic activity of Allium cepa root tips.  

PubMed

The genotoxic and cytotoxic effects of exogenous polyamines (PAs), putrescine (Put), spermidine (Spd), spermine (Spm) and PA biosynthetic inhibitors, alpha-difluoromethylornithine (DFMO), cyclohexilamine (CHA), methylglioxal bis-(guanylhydrazone) (MGBG) were investigated in the root meristems of Allium cepa L. The reduction of mitotic index and the induction of chromosomal aberrations such as bridges, stickiness, c-mitotic anaphases, micronuclei, endoredupliction by PAs and PA biosynthetic inhibitors were observed and these were used as evidence of genotoxicity and cytotoxicity. PMID:18401948

Unal, Meral; Palavan-Unsal, Narcin; Tufekci, M A

2008-03-01

301

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

PubMed Central

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

Walsh, Charles J.

2012-01-01

302

Manipulating Mitotic Recombination in the Zebrafish Embryo Through RecQ Helicases  

PubMed Central

RecQ DNA helicases resolve Rad-51-mediated recombination and suppress aberrant homologous recombination. RecQ gene loss is associated with cancer susceptibility and increased mitotic recombination. We have developed an in vivo assay based on a zebrafish pigment mutant for suppression of RecQ activity, and demonstrate that zebrafish RecQ genes have conserved function in suppressing mitotic recombination. PMID:17483412

Xie, Jing; Bessling, Seneca L.; Cooper, Timothy K.; Dietz, Harry C.; McCallion, Andrew S.; Fisher, Shannon

2007-01-01

303

Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization†  

PubMed Central

We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2. PMID:20936789

2010-01-01

304

Realizing one-dimensional quantum and high-frequency transport features in aligned single-walled carbon nanotube ropes  

NASA Astrophysics Data System (ADS)

The superiority of the electronic transport properties of single-walled carbon nanotube (SWNT) ropes over SWNT mats is verified from low temperature and frequency-dependent transport. The overall change of resistance versus in nanotube mats shows that 3D variable range hopping is the dominant conduction mechanism within the 2-300 K range. The magneto-resistance (MR) is found to be predominantly negative with a parabolic nature, which can also be described by the hopping model. Although the positive upturn of the MR at low temperatures establishes the contribution from quantum interference, the inherent quantum transport in individual tubes is suppressed at elevated temperatures. Therefore, to minimize multi-channel effects from inter-tube interactions and other defects, two-terminal devices were fabricated from aligned SWNT (extracted from a mat) for low temperature transport as well as high-frequency measurements. In contrast to the mat, the aligned ropes exhibit step-like features in the differential conductance within the 80-300 K temperature range. The effects of plasmon propagation, unique to one dimension, were identified in electronic transport as a non-universal power-law dependence of the differential conductance on temperature and source-drain voltage. The complex impedance showed high power transmission capabilities up to 65 GHz as well as oscillations in the frequency range up to 30 GHz. The measurements suggest that aligned SWNT ropes have a realistic potential for high-speed device applications.

Ncube, Siphephile; Chimowa, George; Chiguvare, Zivayi; Bhattacharyya, Somnath

2014-07-01

305

Spectral, temporal and temperature features of the nonlinear response of high-temperature superconductors in transient nonlinear spectroscopy  

SciTech Connect

It is shown that basic properties of the nonlinear response of high-temperature superconductors (HTSCs) observed in femtosecond and picosecond pump-probe experiments at high and low pump levels in various variants of the pump-probe spectroscopy, including one- and two-photon excited-state probing, can be interpreted by using two assumptions. The spectral and temperature properties of the HTSC response at low pump levels can be explained taking into account the contributions from interband electronic transitions to the dielectric constant. At the same time, drastic variations in the HTSC response kinetics (temporal features) observed at high pump levels (for a typical pump pulse energy of {approx}10{sup -7} J in a focal spot of diameter 150 {mu}m) can be explained by assuming the existence of a 'frozen' (metastable) energy gap in the electronic spectrum of a HTSC. In this case, all the conditions required for the interpretation of a drastic decrease in the relaxation rate of a nonlinear response (degeneracy) are realised due to the specific distribution of the electronic state density immediately after the formation of the energy gap in the electronic spectrum of the HTSC. (review)

Bobyrev, Yu V; Petnikova, V M; Rudenko, K V; Shuvalov, Vladimir V [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation)

2006-10-31

306

Kinesin-13 regulates flagellar, interphase, and mitotic microtubule dynamics in Giardia intestinalis.  

PubMed

Microtubule depolymerization dynamics in the spindle are regulated by kinesin-13, a nonprocessive kinesin motor protein that depolymerizes microtubules at the plus and minus ends. Here we show that a single kinesin-13 homolog regulates flagellar length dynamics, as well as other interphase and mitotic dynamics in Giardia intestinalis, a widespread parasitic diplomonad protist. Both green fluorescent protein-tagged kinesin-13 and EB1 (a plus-end tracking protein) localize to the plus ends of mitotic and interphase microtubules, including a novel localization to the eight flagellar tips, cytoplasmic anterior axonemes, and the median body. The ectopic expression of a kinesin-13 (S280N) rigor mutant construct caused significant elongation of the eight flagella with significant decreases in the median body volume and resulted in mitotic defects. Notably, drugs that disrupt normal interphase and mitotic microtubule dynamics also affected flagellar length in Giardia. Our study extends recent work on interphase and mitotic kinesin-13 functioning in metazoans to include a role in regulating flagellar length dynamics. We suggest that kinesin-13 universally regulates both mitotic and interphase microtubule dynamics in diverse microbial eukaryotes and propose that axonemal microtubules are subject to the same regulation of microtubule dynamics as other dynamic microtubule arrays. Finally, the present study represents the first use of a dominant-negative strategy to disrupt normal protein function in Giardia and provides important insights into giardial microtubule dynamics with relevance to the development of antigiardial compounds that target critical functions of kinesins in the giardial life cycle. PMID:17766466

Dawson, Scott C; Sagolla, Meredith S; Mancuso, Joel J; Woessner, David J; House, Susan A; Fritz-Laylin, Lillian; Cande, W Zacheus

2007-12-01

307

Inactivation of Mitotic Kinase Triggers Translocation of MEN Components to Mother-Daughter Neck in Yeast  

PubMed Central

Chromosome segregation, mitotic exit, and cytokinesis are executed in this order during mitosis. Although a scheme coordinating sister chromatid separation and initiation of mitotic exit has been proposed, the mechanism that temporally links the onset of cytokinesis to mitotic exit is not known. Exit from mitosis is regulated by the mitotic exit network (MEN), which includes a GTPase (Tem1) and various kinases (Cdc15, Cdc5, Dbf2, and Dbf20). Here, we show that Dbf2 and Dbf20 functions are necessary for the execution of cytokinesis. Relocalization of these proteins from spindle pole bodies to mother daughter neck seems to be necessary for this role because cdc15-2 mutant cells, though capable of exiting mitosis at semipermissive temperature, are unable to localize Dbf2 (and Dbf20) to the “neck” and fail to undergo cytokinesis. These cells can assemble and constrict the actomyosin ring normally but are incapable of forming a septum, suggesting that MEN components are critical for the initiation of septum formation. Interestingly, the spindle pole body to neck translocation of Dbf2 and Dbf20 is triggered by the inactivation of mitotic kinase. The requirement of kinase inactivation for translocation of MEN components to the division site thus provides a mechanism that renders mitotic exit a prerequisite for cytokinesis. PMID:12937277

Hwa Lim, Hong; Yeong, Foong May; Surana, Uttam

2003-01-01

308

An unusual DNA binding compound, S23906, induces mitotic catastrophe in cultured human cells.  

PubMed

The biochemical pathways that lead cells to mitotic catastrophe are not well understood. To identify these pathways, we have taken an approach of treating cells with a novel genotoxic compound and characterizing whether cells enter mitotic catastrophe or not. S23906 is a novel acronycine derivative that forms adducts with the N2 residue of guanine in the minor groove of the DNA helix and destabilizes base pairing to cause helix opening. We observed, in HeLa and HT-29 cells, that S23906 induced gamma-H2AX and activated checkpoint kinase 1, as did bleomycin, camptothecin, and cisplatin, when tested under equi-toxic conditions. S23906 also induced cyclin E1 protein, although this activity was not required for cytotoxicity because knock down of cyclin E1 by RNA interference did not affect the number of dead cells after treatment. Cyclin B1 levels first decreased and then increased after treatment with S23906. Cyclin B1 was associated with Cdk1 kinase activity, which correlated with an increase in the number of mitotic cells. By 32 h after treatment, at least 20% of the cells entered mitotic catastrophe as determined by microscopy. Suppression of the DNA checkpoint response by co-treatment with caffeine increased the number of cells in mitosis. These results suggest that mitotic catastrophe is one of the cellular responses to S23906 and that mitotic catastrophe may be a common cellular response to many different types of DNA damage. PMID:19758748

Cahuzac, Nathalie; Studény, Aurélie; Marshall, Kris; Versteege, Isabella; Wetenhall, Kate; Pfeiffer, Bruno; Léonce, Stéphane; Hickman, John A; Pierré, Alain; Golsteyn, Roy M

2010-03-28

309

MTBP plays a crucial role in mitotic progression and chromosome segregation  

PubMed Central

Murine double minute 2 (MDM2) binding protein (MTBP) has been implicated in tumor cell proliferation, but the underlying mechanisms remain unclear. The results of MTBP expression analysis during cell cycle progression demonstrated that MTBP protein was rapidly degraded during mitosis. Immunofluorescence studies revealed that a portion of MTBP was localized at the kinetochores during prometaphase. MTBP overexpression delayed mitotic progression from nuclear envelope breakdown (NEB) to anaphase onset and induced abnormal chromosome segregation such as lagging chromosomes, chromosome bridges, and multipolar chromosome segregation. Conversely, MTBP downmodulation caused an abbreviated metaphase and insufficient mitotic arrest, resulting in abnormal chromosome segregation, aneuploidy, decreased cell proliferation, senescence, and cell death, similar to that of Mad2 (mitotic arrest-deficient 2) downmodulation. Furthermore, MTBP downmodulation inhibited the accumulation of Mad1 and Mad2, but not BubR1 (budding uninhibited by benzimidazoles related 1), on the kinetochores, whereas MTBP overexpression inhibited the release of Mad2 from the metaphase kinetochores. These results may imply that MTBP has an important role in recruiting and/or retaining the Mad1/Mad2 complex at the kinetochores during prometaphase, but its degradation is required for silencing the mitotic checkpoint. Together, this study indicates that MTBP has a crucial role in proper mitotic progression and faithful chromosome segregation, providing new insights into regulation of the mitotic checkpoint. PMID:21274008

Agarwal, N; Tochigi, Y; Adhikari, A S; Cui, S; Cui, Y; Iwakuma, T

2011-01-01

310

Procedures used in the induction of mitotic recombination and mutation in the yeast Saccharomyces cerevisiae.  

PubMed

Techniques are described for the use of various yeast strains to detect the induction of (1) mitotic crossing-over, (2) mitotic gene conversion, (3) forward mutation and (4) reverse mutation. The technique for the detection of mitotic crossing over is based on a diploid that carries two different alleles of the gene locus ade2. These alleles differ in their extent of colony pigmentation engendered on low-adenine media, and they complement each other to the effect that the diploid is white. Mitotic crossing over results in the formation of twin-sectored colonies with a red and a pink sector. The technique for the detection of mitotic gene conversion is based on the use of a heteroallelic diploid carrying two non-complementing alleles that cause a nutritional requirement. Mitotic gene conversion leads to the restoration of intact and dominant wild-type alleles that alleviate the nutritional requirement so that convertant cells can be selected on a minimal medium. The forward mutation technique is based on the use of a haploid strain with a defect in the ade2-gene locus which causes the formation of red colonies. Induction of forward mutation in a number of other loci prevents the accumulation of this red pigment so that induction of mutation can be detected by the formation of pink and white colonies. The reverse mutation technique is based on the restoration or compensation of a mutational defect causing a growth requirement. Mutants can be selected for on a minimal medium. PMID:235086

Zimmermann, F K

1975-04-01

311

MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.  

PubMed

Greatwall (Gwl) was originally discovered in Drosophila as an essential kinase for correct chromosome condensation and mitotic progression. In Xenopus, Gwl may influence the positive-feedback loop that directs cyclin B1-Cdk1 activation and the mitotic state by inhibiting the phosphatase PP 2A. Here, we describe the human orthologue of Gwl called microtubule-associated serine/threonine kinase-like (MASTL). We found that MASTL localizes to the nucleus in interphase and re-localizes in part to centrosomes in mitosis, when it is active. Cells strongly depleted of MASTL by RNAi delay in G(2) phase and reveal slow chromosome condensation. MASTL RNAi cells that enter and progress through mitosis often fail to completely separate their sister chromatids in anaphase. This causes chromatin to be trapped in the cleavage furrow, which may lead to the formation of 4N G(1) cells by cytokinesis failure. Further, our experiments indicate that MASTL supports the phosphorylation state of mitotic phospho-proteins downstream of cyclin B1-Cdk1, including the APC/C. Cyclin B1 destruction is incomplete when mitotic cells that are strongly depleted of MASTL exit mitosis. We propose that MASTL enhances cyclin B1-Cdk1-dependent mitotic phosphorylation events, directing mitotic entry, anaphase and cytokinesis in human cells. PMID:20818157

Voets, Erik; Wolthuis, Rob M F

2010-09-01

312

The discovery and optimization of hexahydro-2 H-pyrano[3,2- c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5  

Microsoft Academic Search

Here we describe the discovery and optimization of hexahydro-2H-pyrano[3,2-c]quinolines (HHPQs) as potent and selective inhibitors of the mitotic kinesin-5 originally found during a high-throughput screening (HTS) campaign sampling our in-house compound collection. The compounds optimized subsequently and characterized herein were potently inhibiting the ATPase activity of Kinesin-5 and also exhibited consistent cellular activity, in that cells arrested in mitosis and

Kai Schiemann; Dirk Finsinger; Frank Zenke; Christiane Amendt; Thorsten Knöchel; David Bruge; Hans-Peter Buchstaller; Ulrich Emde; Wolfgang Stähle; Soheila Anzali

2010-01-01

313

Prevalence and clinical features of Thought-Perception-Sensitivity Symptoms: results from a community survey of Korean high school students.  

PubMed

Epidemiologic research indicates that psychosis and depression most frequently develop during adolescence. Hence, an efficient strategy for improving youth mental health would be to focus on detection of early-stage psychosis and depression in adolescence. In this study, 1461 high school students were surveyed using self-report scales. Students who scored equal to or above the cut-off value on any of the scales and who agreed to a further examination proceeded to a second assessment, using the Kiddie Schedule for Affective Disorders and Schizophrenia and Comprehensive Assessment of At-Risk Mental States along with self-reporting scales. The estimated prevalence of adolescents at ultra-high risk (UHR) for psychosis and of depression-spectrum disorders was 1.26 and 3.69% respectively. Compared with the normal group, experiences of bullying, suicidal ideation, and suicide attempts were significantly higher in these two groups; the subjects at UHR for psychosis were found to have significantly lower academic performance and lower ratings on SCRS; and submissive behavior was more prevalent in the depression-spectrum group. Our results reveal several clinical features of adolescents at UHR for psychosis and with depression-spectrum disorder and underscore the importance of accurate assessment of and early appropriate care for these adolescents. PMID:22475525

Kang, Nam-In; Park, Tae-Won; Yang, Jong-Chul; Oh, Keun-Young; Shim, Shi-Ha; Chung, Young-Chul

2012-08-15

314

Modification of the large-scale features of high Reynolds number wall turbulence by passive surface obtrusions  

NASA Astrophysics Data System (ADS)

A high Reynolds number boundary-layer wind-tunnel facility at New Mexico State University was fitted with a regularly distributed braille surface. The surface was such that braille dots were closely packed in the streamwise direction and sparsely spaced in the spanwise direction. This novel surface had an unexpected influence on the flow: the energy of the very large-scale features of wall turbulence (approximately six-times the boundary-layer thickness in length) became significantly attenuated, even into the logarithmic region. To the author's knowledge, this is the first experimental study to report a modification of `superstructures' in a rough-wall turbulent boundary layer. The result gives rise to the possibility that flow control through very small, passive surface roughness may be possible at high Reynolds numbers, without the prohibitive drag penalty anticipated heretofore. Evidence was also found for the uninhibited existence of the near-wall cycle, well known to smooth-wall-turbulence researchers, in the spanwise space between roughness elements.

Monty, J. P.; Allen, J. J.; Lien, K.; Chong, M. S.

2011-12-01

315

Design and operating features of the high-level waste vitrification system for the West Valley demonstration project  

SciTech Connect

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.

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

316

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

NASA Astrophysics Data System (ADS)

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.

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

2009-04-01

317

Genetic requirements for spontaneous and transcription-stimulated mitotic recombination in Saccharomyces cerevisiae.  

PubMed Central

The genetic requirements for spontaneous and transcription-stimulated mitotic recombination were determined using a recombination system that employs heterochromosomal lys2 substrates that can recombine only by crossover or only by gene conversion. The substrates were fused either to a constitutive low-level promoter (pLYS) or to a highly inducible promoter (pGAL). In the case of the "conversion-only" substrates the use of heterologous promoters allowed either the donor or the recipient allele to be highly transcribed. Transcription of the donor allele stimulated gene conversions in rad50, rad51, rad54, and rad59 mutants, but not in rad52, rad55, and rad57 mutants. In contrast, transcription of the recipient allele stimulated gene conversions in rad50, rad51, rad54, rad55, rad57, and rad59 mutants, but not in rad52 mutants. Finally, transcription stimulated crossovers in rad50, rad54, and rad59 mutants, but not in rad51, rad52, rad55, and rad57 mutants. These data are considered in relation to previously proposed molecular mechanisms of transcription-stimulated recombination and in relation to the roles of the recombination proteins. PMID:12242220

Freedman, Jennifer A; Jinks-Robertson, Sue

2002-01-01

318

The development of wing shape in Lepidoptera: mitotic density, not orientation, is the primary determinant of shape.  

PubMed

The wings of butterflies and moths develop from imaginal disks whose structure is always congruent with the final adult wing. It is therefore possible to map every point on the imaginal disk to a location on the adult wing throughout ontogeny. We studied the growth patterns of the wings of two distantly related species with very different adult wing shapes, Junonia coenia and Manduca sexta. The shape of the wing disks change throughout their growth phase in a species-specific pattern. We measured mitotic densities and mitotic orientation in successive stages of wing development approximately one cell division apart. Cell proliferation was spatially patterned, and the density of mitoses was highly correlated with local growth. Unlike other systems in which the direction of mitoses has been viewed as the primary determinant of directional growth, we found that in these two species the direction of growth was only weakly correlated with the orientation of mitoses. Directional growth appears to be imposed by a constantly changing spatial pattern of cell division coupled with a weak bias in the orientation of cell division. Because growth and cell division in imaginal disk require ecdysone and insulin signaling, the changing spatial pattern of cell division may due to a changing pattern of expression of receptors or downstream elements in the signaling pathways for one or both of these hormones. Evolution of wing shape comes about by changes in the progression of spatial patterns of cell division. PMID:24617986

Nijhout, H Frederik; Cinderella, Margaret; Grunert, Laura W

2014-03-01

319

Clinical Factors Associated With High-Risk Carotid Plaque Features as Assessed by Magnetic Resonance Imaging in Patients With Established Vascular Disease (from the AIM-HIGH Study).  

PubMed

Association between clinical factors and high-risk plaque features, such as, thin or ruptured cap, intraplaque hemorrhage, presence of lipid-rich necrotic core (LRNC), and increased LRNC volume as assessed by magnetic resonance imaging (MRI), was examined in patients with established vascular disease in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides (AIM-HIGH) trial. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents, and MRI-modified American Heart Association lesion type by a core laboratory. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced American Heart Association type-VI lesions with possible surface defect, intraplaque hemorrhage, or mural thrombus. Type-VI lesions were associated with older age (odds ratio [OR] = 2.6 per 5 years increase, p <0.001). After adjusting for age, these lesions were associated with history of cerebrovascular disease (OR = 4.1, p = 0.01), higher levels of lipoprotein(a) (OR = 2.0 per 1 SD increase, p = 0.02), and larger percent wall volume (PWV [OR = 4.6 per 1 SD increase, p <0.001]) but, were negatively associated with metabolic syndrome (OR = 0.2, p = 0.02). Presence of LRNC was associated with the male gender (OR = 3.2, p = 0.02) and PWV (OR = 3.8 per 1 SD, p <0.001); however, it was negatively associated with diabetes (OR = 0.4, p = 0.02) and high-density lipoprotein cholesterol levels (OR = 0.7 per 1 SD, p = 0.02). Increased percent LRNC was associated with PWV (regression coefficient = 0.36, p <0.001) and negatively associated with ApoA1 levels (regression coefficient = -0.20, p = 0.03). In conclusion, older age, male gender, history of cerebrovascular disease, larger plaque burden, higher lipoprotein(a), and lower high-density lipoprotein cholesterol or ApoA1 level have statistically significant associations with high-risk plaque features. Metabolic syndrome and diabetes showed negative associations in this population. PMID:25245415

Zhao, Xue-Qiao; Hatsukami, Thomas S; Hippe, Daniel S; Sun, Jie; Balu, Niranjan; Isquith, Daniel A; Crouse, John R; Anderson, Todd; Huston, John; Polissar, Nayak; O'Brien, Kevin; Yuan, Chun

2014-11-01

320

EAM-based high-speed 100-km OFDM transmission featuring tolerant modulator operation enabled using SSII cancellation.  

PubMed

In this study, a technique was developed to compensate for nonlinear distortion through cancelling subcarrier-to-subcarrier intermixing interference (SSII) in an electroabsorption modulator (EAM)-based orthogonal frequency-division multiplexing (OFDM) transmission system. The nonlinear distortion to be compensated for is induced by both EAM nonlinearity and fiber dispersion. Because an OFDM signal features an inherently high peak-to-average power ratio, a trade-off exists between the optical modulation index (OMI) and modulator nonlinearity. Therefore, the nonlinear distortion limits the operational tolerance of the bias voltage and the driving power to a small region. After applying the proposed SSII cancellation, the OMI of an OFDM signal was increased yielding only a small increment of nonlinear distortion, and the tolerance region of the operational conditions was also increased. By employing the proposed scheme, this study successfully demonstrates 50-Gbps OFDM transmission over 100-km dispersion-uncompensated single-mode fiber based on a single 10-GHz EAM. PMID:24977559

Chen, Hsing-Yu; Wei, Chia-Chien; Lu, I-Cheng; Chen, Yu-Chao; Chu, Hsuan-Hao; Chen, Jyehong

2014-06-16

321

Mitotically active proliferative nodule arising in a giant congenital melanocytic nevus: a diagnostic pitfall.  

PubMed

Proliferative (cellular) nodules (PN) which mimic malignant melanoma clinically and histologically are described in congenital melanocytic nevi (CMN) and may pose significant diagnostic challenges. We report the case of a 10-day-old male with a giant congenital nevus involving the neck, upper chest, back, and left shoulder containing several nodular lesions, some crusted. Biopsy of a nodule revealed densely packed nevus cells with hyperchromatic round to oval and occasionally irregularly shaped nuclei. There was no necrosis or pushing border, and the nodule blended with the adjacent nevus; however, the lesion demonstrated a significant number of mitoses (27 per mm2) and a 60% labeling index with Ki-67. Further analysis by fluorescence in situ hybridization (FISH) with a 4-color probe set targeting 6p25, 6q23, 11q13, and centromere 6 revealed increased chromosomal copy numbers of all 4 probes, which was interpreted as evidence of polyploidy. In addition, analysis of DNA copy number changes using a single nucleotide polymorphism microarray (Affymetrix, Santa Clara, CA) showed no chromosomal aberrations. The diagnosis of PN in a giant congenital nevus was eventually rendered. At 13-month follow-up, the nodules showed no evidence of growth. Our case illustrates that PNs in the neonatal period might demonstrate extreme mitotic activity. This feature is worrisome when encountered in melanocytic lesions; however, it should not trigger by itself a diagnosis of melanoma in the absence of other histologic criteria of malignancy. In addition, we document polyploidy by FISH in PN, which can potentially be misinterpreted as a FISH-positive result. PMID:23348144

Nguyen, Thuy L T; Theos, Amy; Kelly, David R; Busam, Klaus; Andea, Aleodor A

2013-02-01

322

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

SciTech Connect

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.

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

323

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

PubMed Central

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

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

2012-01-01

324

Computer simulations predict that chromosome movements and rotations accelerate mitotic spindle assembly without compromising accuracy  

PubMed Central

The mitotic spindle self-assembles in prometaphase by a combination of centrosomal pathway, in which dynamically unstable microtubules search in space until chromosomes are captured, and a chromosomal pathway, in which microtubules grow from chromosomes and focus to the spindle poles. Quantitative mechanistic understanding of how spindle assembly can be both fast and accurate is lacking. Specifically, it is unclear how, if at all, chromosome movements and combining the centrosomal and chromosomal pathways affect the assembly speed and accuracy. We used computer simulations and high-resolution microscopy to test plausible pathways of spindle assembly in realistic geometry. Our results suggest that an optimal combination of centrosomal and chromosomal pathways, spatially biased microtubule growth, and chromosome movements and rotations is needed to complete prometaphase in 10–20 min while keeping erroneous merotelic attachments down to a few percent. The simulations also provide kinetic constraints for alternative error correction mechanisms, shed light on the dual role of chromosome arm volume, and compare well with experimental data for bipolar and multipolar HT-29 colorectal cancer cells. PMID:19717443

Paul, Raja; Wollman, Roy; Silkworth, William T.; Nardi, Isaac K.; Cimini, Daniela; Mogilner, Alex

2009-01-01

325

Starvation induces FoxO-dependent mitotic-to-endocycle switch pausing during Drosophila oogenesis.  

PubMed

When exposed to nutrient challenge, organisms have to adapt their physiology in order to balance reproduction with adult fitness. In mammals, ovarian follicles enter a massive growth phase during which they become highly dependent on gonadotrophic factors and nutrients. Somatic tissues play a crucial role in integrating these signals, controlling ovarian follicle atresia and eventually leading to the selection of a single follicle for ovulation. We used Drosophila follicles as a model to study the effect of starvation on follicle maturation. Upon starvation, Drosophila vitellogenic follicles adopt an 'atresia-like' behavior, in which some slow down their development whereas others enter degeneration. The mitotic-to-endocycle (M/E) transition is a critical step during Drosophila oogenesis, allowing the entry of egg chambers into vitellogenesis. Here, we describe a specific and transient phase during M/E switching that is paused upon starvation. The Insulin pathway induces the pausing of the M/E switch, blocking the entry of egg chambers into vitellogenesis. Pausing of the M/E switch involves a previously unknown crosstalk between FoxO, Cut and Notch that ensures full reversion of the process and rapid resumption of oogenesis upon refeeding. Our work reveals a novel genetic mechanism controlling the extent of the M/E switch upon starvation, thus integrating metabolic cues with development, growth and reproduction. PMID:24993942

Jouandin, Patrick; Ghiglione, Christian; Noselli, Stéphane

2014-08-01

326

Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo  

PubMed Central

Background The Ewing sarcoma breakpoint region 1 gene (EWSR1), also known as EWS, is fused to a number of different partner genes as a result of chromosomal translocation in diverse sarcomas. Despite the involvement of EWSR1 in these diverse sarcomas, the in vivo function of wild type EWSR1 remains unclear. Principal Findings We identified two zebrafish EWSR1 orthologues, ewsr1a and ewsr1b, and demonstrate that both genes are expressed maternally, and are expressed ubiquitously throughout zebrafish embryonic development. Morpholino induced knockdown of both zebrafish ewsr1 genes led to mitotic defects with multipolar or otherwise abnormal mitotic spindles starting from the bud stage (10 hour post-fertilization (hpf)). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish and human. Conclusions Ewsr1 maintains mitotic integrity and proneural cell survival in early zebrafish development. PMID:17912356

Azuma, Mizuki; Embree, Lisa J.; Sabaawy, Hatem; Hickstein, Dennis D.

2007-01-01

327

Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21Cip1  

PubMed Central

Aurora kinase B is a critical component of the chromosomal passenger complex, which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis. By using conditional knockout cells and chemical inhibition, we show here that inactivation of Aurora B results in delayed G1/S transition and premature mitotic exit. Aurora B deficiency results in delayed DNA replication in cultured fibroblasts as well as liver cells after hepatectomy. This is accompanied by increased transcription of the cell cycle inhibitor p21Cip1. Lack of Aurora B does not prevent mitotic entry but results in a premature exit from prometaphase in the presence of increased p21Cip1-Cdk1 inactive complexes. Aurora B-null cells display reduced degradation of cyclin B1, suggesting the presence of phenomenon known as adaptation to the mitotic checkpoint, previously described in yeast. Elimination of p21Cip1 rescues Cdk1 activity and prevents premature mitotic exit in Aurora B-deficient cells. These results suggest that Aurora B represses p21Cip1, preventing delayed DNA replication, Cdk inhibition and premature mitotic exit. The upregulation of p21Cip1 observed after inhibition of Aurora B may have important implications in cell cycle progression, tetraploidy, senescence or cancer therapy. PMID:23428904

Trakala, Marianna; Fernández-Miranda, Gonzalo; Pérez de Castro, Ignacio; Heeschen, Christopher; Malumbres, Marcos

2013-01-01

328

The KASH protein Kms2 coordinates mitotic remodeling of the spindle pole body.  

PubMed

Defects in the biogenesis of the spindle pole body (SPB), the yeast centrosome equivalent, can lead to monopolar spindles and mitotic catastrophe. The KASH domain protein Kms2 and the SUN domain protein Sad1 colocalize within the nuclear envelope at the site of SPB attachment during interphase and at the spindle poles during mitosis in Schizosaccharomyces pombe. We show that Kms2 interacts with the essential SPB components Cut12 and Pcp1 and the Polo kinase Plo1. Depletion of Kms2 delays mitotic entry and leads to defects in the insertion of the SPB into the nuclear envelope, disrupting stable bipolar spindle formation. These effects are mediated in part by a delay in the recruitment of Plo1 to the SPB at mitotic entry. Plo1 activity supports mitotic SPB remodeling by driving a burst of incorporation of Cut12 and Pcp1. Thus, a fission yeast SUN-KASH complex plays an important role in supporting the remodeling of the SPB at mitotic entry. PMID:24963130

Wälde, Sarah; King, Megan C

2014-08-15

329

Systematic Deletion and Mitotic Localization of the Nuclear Pore Complex Proteins of Aspergillus nidulans  

PubMed Central

To define the extent of the modification of the nuclear pore complex (NPC) during Aspergillus nidulans closed mitosis, a systematic analysis of nuclear transport genes has been completed. Thirty genes have been deleted defining 12 nonessential and 18 essential genes. Several of the nonessential deletions caused conditional phenotypes and self-sterility, whereas deletion of some essential genes caused defects in nuclear structure. Live cell imaging of endogenously tagged NPC proteins (Nups) revealed that during mitosis 14 predicted peripheral Nups, including all FG repeat Nups, disperse throughout the cell. A core mitotic NPC structure consisting of membrane Nups, all components of the An-Nup84 subcomplex, An-Nup170, and surprisingly, An-Gle1 remained throughout mitosis. We propose this minimal mitotic NPC core provides a conduit across the nuclear envelope and acts as a scaffold to which dispersed Nups return during mitotic exit. Further, unlike other dispersed Nups, An-Nup2 locates exclusively to mitotic chromatin, suggesting it may have a novel mitotic role in addition to its nuclear transport functions. Importantly, its deletion causes lethality and defects in DNA segregation. This work defines the dramatic changes in NPC composition during A. nidulans mitosis and provides insight into how NPC disassembly may be integrated with mitosis. PMID:16987955

Osmani, Aysha H.; Davies, Jonathan; Liu, Hui-Lin; Nile, Aaron

2006-01-01

330

Cyclin B1 Overexpression Induces Cell Death Independent of Mitotic Arrest  

PubMed Central

Microtubule inhibitors are widely used in cancer chemotherapy. These drugs characteristically induce mitotic arrest and cell death but the mechanisms linking the two are not firmly established. One of the problems is that cancer cells vary widely in their sensitivity to these agents, and thus comparison of data from different systems is difficult. To alleviate this problem we sought to molecularly induce mitotic death and study its mechanisms, by expressing non-degradable cyclin B (R42A) in HeLa cells. However, this approach failed to induce significant mitotic arrest, Cdk1 activation, or phosphorylation of anti-apoptotic Bcl-2 proteins, all characteristics of cells treated with microtubule inhibitors. Furthermore, cyclin B1-R42A induced rapid cell death, and when expressed in synchronized cells, cell death occurred in G1 phase. Decreasing the plasmid concentration reduced transfection efficiency but restored mitotic arrest and eliminated non-specific death. These results show that inappropriate overexpression of cyclin B1 causes non-specific cell death and suggest caution in its use for the study of mitotic events. PMID:25415322

Eichhorn, Joshua M.; Kothari, Anisha; Chambers, Timothy C.

2014-01-01

331

Long-Tract Mitotic Gene Conversion in Yeast: Evidence for a Triparental Contribution during Spontaneous Recombination  

PubMed Central

In Saccharomyces cerevisiae, spontaneous mitotic gene conversion at one site is statistically correlated with recombination at other loci. In general, coincident conversion frequencies are highest for tightly linked markers and decline as a function of intermarker distance. Paradoxically, a significant fraction of mitotic gene convertants exhibits concomitant nonreciprocal segregation for multiple and widely spaced markers. We have undertaken a detailed genetic analysis of this class of mitotic recombinants. Our results indicate that mitotic gene conversion in yeast is frequently associated with nonreciprocal segregation of markers centromere-distal to the selected site of conversion. In addition, distal markers are often found to be mosaic within the product colonies. These observations, and others described here, suggest that a percentage of gene conversion in vegetative yeast cells is coupled to a chromosome break and repair mechanism. This hypothesis was further tested using a strain trisomic for chromosome VII which was specially marked to detect homolog-dependent repair events. An association between mitotic gene conversion events and the production of broken chromosomes which are repaired by a homologous-pairing-copy mechanism was supported. PMID:8070656

Bethke, B. D.; Golin, J.

1994-01-01

332

A computational model for the formation of lamin-B mitotic spindle envelope and matrix.  

PubMed

Recent reports show that, after nuclear envelope breakdown, lamin-B, a component of the nuclear lamina in interphase, localizes around the mitotic spindle as a membranous network. How this process occurs, however, and how it influences mitotic spindle morphogenesis is unclear. Here, we develop a computational model based on a continuum description to represent the abundance and location of various molecular species involved during mitosis, and use the model to test a number of hypotheses regarding the formation of the mitotic matrix. Our model illustrates that freely diffusible nuclear proteins can be captured and transported to the spindle poles by minus-end-directed microtubule (MT) motors. Moreover, simulations show that these proteins can be used to build a shell-like region that envelopes the mitotic spindle, which helps to improve the focusing of the mitotic spindle by spatially restricting MT polymerization and limiting the effective diffusion of the free MTs. Simulations also confirm that spatially dependent regulation of the spindle network through the Ran system improves spindle focusing and morphology. Our results agree with experimental observations that lamin-B reorganizes around the spindle and helps to maintain spindle morphology. PMID:24904732

Shi, Changji; Channels, Wilbur E; Zheng, Yixian; Iglesias, Pablo A

2014-06-01

333

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

PubMed

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

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

2014-01-01

334

Effect of tumor promoters on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae.  

PubMed

Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodoacetate, anthralin, and 12-O-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-O-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters. PMID:6992984

Kunz, B A; Hannan, M A; Haynes, R H

1980-07-01

335

CDK11p58 Is Required for Centriole Duplication and Plk4 Recruitment to Mitotic Centrosomes  

PubMed Central

Background CDK11p58 is a mitotic protein kinase, which has been shown to be required for different mitotic events such as centrosome maturation, chromatid cohesion and cytokinesis. Methodology/Principal Findings In addition to these previously described roles, our study shows that CDK11p58 inhibition induces a failure in the centriole duplication process in different human cell lines. We propose that this effect is mediated by the defective centrosomal recruitment of proteins at the onset of mitosis. Indeed, Plk4 protein kinase and the centrosomal protein Cep192, which are key components of the centriole duplication machinery, showed reduced levels at centrosomes of mitotic CDK11-depleted cells. CDK11p58, which accumulates only in the vicinity of mitotic centrosomes, directly interacts with the centriole-associated protein kinase Plk4 that regulates centriole number in cells. In addition, we show that centriole from CDK11 defective cells are not able to be over duplicated following Plk4 overexpression. Conclusion/Significance We thus propose that CDK11 is required for centriole duplication by two non-mutually-exclusive mechanisms. On one hand, the observed duplication defect could be caused indirectly by a failure of the centrosome to fully maturate during mitosis. On the other hand, CDK11p58 could also directly regulate key centriole components such as Plk4 during mitosis to trigger essential mitotic centriole modifications, required for centriole duplication during subsequent interphase. PMID:21297952

Rome, Pierre; Pascal, Aude; Cremet, Jean-Yves; Giet, Regis

2011-01-01

336

Plk1-Dependent Recruitment of ?-Tubulin Complexes to Mitotic Centrosomes Involves Multiple PCM Components  

PubMed Central

The nucleation of microtubules requires protein complexes containing ?-tubulin, which are present in the cytoplasm and associate with the centrosome and with the mitotic spindle. We have previously shown that these interactions require the ?-tubulin targeting factor GCP-WD/NEDD1, which has an essential role in spindle formation. The recruitment of additional ?-tubulin to the centrosomes occurs during centrosome maturation at the G2/M transition and is regulated by the mitotic kinase Plk1. However, the molecular details of this important pathway are unknown and a Plk1 substrate that controls ?-tubulin recruitment has not been identified. Here we show that Plk1 associates with GCP-WD in mitosis and Plk1 activity contributes to phosphorylation of GCP-WD. Plk1 depletion or inhibition prevents accumulation of GCP-WD at mitotic centrosomes, but GCP-WD mutants that are defective in Plk1-binding and -phosphorylation still accumulate at mitotic centrosomes and recruit ?-tubulin. Moreover, Plk1 also controls the recruitment of other PCM proteins implicated in centrosomal ?-tubulin attachment (Cep192/hSPD2, pericentrin, Cep215/Cdk5Rap2). Our results support a model in which Plk1-dependent recruitment of ?-tubulin to mitotic centrosomes is regulated upstream of GCP-WD, involves multiple PCM proteins and therefore potentially multiple Plk1 substrates. PMID:19543530

Haren, Laurence; Stearns, Tim; Luders, Jens

2009-01-01

337

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

PubMed

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

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

2014-01-01

338

In the near future, off-road mobile robots will feature high levels of autonomy which will render them useful for a vari-  

E-print Network

Page 1 Abstract In the near future, off-road mobile robots will feature high levels of autonomy applications have a special demand for robots to possess similar qualities to man-driven machines: high speed approaches that model the soil as a mass-spring system, where the soil granules are considered as point

Kelly, Alonzo

339

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

PubMed Central

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

Miyamoto, M; Tanaka, K; Okayama, H

1994-01-01

340

The Caenorhabditis elegans Aurora B Kinase AIR-2 Phosphorylates and Is Required for the Localization of a BimC Kinesin to Meiotic and Mitotic SpindlesD?  

PubMed Central

BimC kinesins are required for mitotic spindle assembly in a variety of organisms. These proteins are localized to centrosomes, spindle microtubules, and the spindle midzone. We have previously shown that the Caenorhabditis elegans Aurora B kinase AIR-2 is required for the localization of the ZEN-4 kinesin protein to midzone microtubules. To determine whether the association of BimC kinesins with spindle microtubules is also dependent on AIR-2, we examined the expression pattern of BMK-1, a C. elegans BimC kinesin, in wild-type and AIR-2–deficient embryos. BMK-1 is highly expressed in the hermaphrodite gonad and is localized to meiotic spindle microtubules in the newly fertilized embryo. In mitotic embryos, BMK-1 is associated with spindle microtubules from prophase through anaphase and is concentrated at the spindle midzone during anaphase and telophase. In the absence of AIR-2, BMK-1 localization to meiotic and mitotic spindles is greatly reduced. This is not a consequence of loss of ZEN-4 localization because BMK-1 is appropriately localized in ZEN-4–deficient embryos. Furthermore, AIR-2 and BMK-1 directly interact with one another and the C-terminal tail domain of BMK-1 is specifically phosphorylated by AIR-2 in vitro. Together with our previous data, these results suggest that at least one function of the Aurora B kinases is to recruit spindle-associated motor proteins to their sites of action. PMID:15548597

Bishop, John D.; Han, Zhenbo; Schumacher, Jill M.

2005-01-01

341

Anthropometric features and body composition of young athletes practicing karate at a high and medium competitive level.  

PubMed

The aim of the study was to examine the anthropometric features and body composition of athletes practising karate at a high and medium competitive level. Our study was carried out on a sample of 35 subjects practising karate and aged from 16.0 to 32.5 years. This sample was divided into two groups: group 1 ( n=14 elite athletes) and group 2 ( n=21 amateur athletes). Various anthropometric measurements were taken (weight, height both standing and sitting, diameters, circumferences and skinfold thickness) from which different anthropometric indices were calculated (body mass index, Scelic and Grant indices, arm muscle circumference and area), and the somatotype was then determined. The body composition of each subject was assessed using the skinfold technique and the Jackson-Pollock (J-P) and Sloan-Weir (S-W) equations. The two groups of athletes showed very similar measurements regarding anthropometric characteristics. Only the Scelix index presented a significantly different value in the two groups (49.6+/-1.3 for group 1 vs. 51.1+/-1.3 for group 2; p<0.01). Group 1 showed a mesomorphic-ectomorphic somatotype, while the amateur athletes presented a balanced mesomorphic type. Moreover, a lower percentage of fat mass was more frequent in the first group (J-P=8.1+/-2.4%; S-W=8.9+/-3.3%) than in the second one (J-P=9.8+/-1.6%; S-W=11.2+/-3.7%), although the differences between the two groups were not significant. We conclude that group 1 is characterized by a slightly prominent vertical development of the skeletal frame. This could be an anthropometric characteristic that is best suited to meet the specific functional requirements of this sport. Moreover, both groups of athletes are characterized by a low percentage of fat mass, particularly the elite group. PMID:14618456

Giampietro, M; Pujia, A; Bertini, I

2003-10-01

342

Low-temperature plasma etching of high aspect-ratio densely packed 15 to sub-10 nm silicon features derived from PS-PDMS block copolymer patterns  

NASA Astrophysics Data System (ADS)

The combination of block copolymer (BCP) lithography and plasma etching offers a gateway to densely packed sub-10 nm features for advanced nanotechnology. Despite the advances in BCP lithography, plasma pattern transfer remains a major challenge. We use controlled and low substrate temperatures during plasma etching of a chromium hard mask and then the underlying substrate as a route to high aspect ratio sub-10 nm silicon features derived from BCP lithography. Siloxane masks were fabricated using poly(styrene-b-siloxane) (PS-PDMS) BCP to create either line-type masks or, with the addition of low molecular weight PS-OH homopolymer, dot-type masks. Temperature control was essential for preventing mask migration and controlling the etched feature’s shape. Vertical silicon wire features (15 nm with feature-to-feature spacing of 26 nm) were etched with aspect ratios up to 17 : 1; higher aspect ratios were limited by the collapse of nanoscale silicon structures. Sub-10 nm fin structures were etched with aspect ratios greater than 10 : 1. Transmission electron microscopy images of the wires reveal a crystalline silicon core with an amorphous surface layer, just slightly thicker than a native oxide.

Liu, Zuwei; Gu, Xiaodan; Hwu, Justin; Sassolini, Simone; Olynick, Deirdre L.

2014-07-01

343

Anticipatory Attentional Suppression of Visual Features Indexed by Oscillatory Alpha-Band Power Increases: A High-Density Electrical Mapping Study  

PubMed Central

Retinotopically specific increases in alpha-band (~10 Hz) oscillatory power have been strongly implicated in the suppression of processing for irrelevant parts of the visual field during the deployment of visuospatial attention. Here, we asked whether this alpha suppression mechanism also plays a role in the nonspatial anticipatory biasing of feature-based attention. Visual word cues informed subjects what the task-relevant feature of an upcoming visual stimulus (S2) was, while high-density electroencephalographic recordings were acquired. We examined anticipatory oscillatory activity in the Cue-to-S2 interval (~2 s). Subjects were cued on a trial-by-trial basis to attend to either the color or direction of motion of an upcoming dot field array, and to respond when they detected that a subset of the dots differed from the majority along the target feature dimension. We used the features of color and motion, expressly because they have well known, spatially separated cortical processing areas, to distinguish shifts in alpha power over areas processing each feature. Alpha power from dorsal regions increased when motion was the irrelevant feature (i.e., color was cued), and alpha power from ventral regions increased when color was irrelevant. Thus, alpha-suppression mechanisms appear to operate during feature-based selection in much the same manner as has been shown for space-based attention. PMID:20237273

Snyder, Adam C.; Foxe, John J.

2010-01-01

344

Mitotic rate of the rat's thyroid gland during hypertrophy induced by an antithyroid agent (carbimazole).  

PubMed Central

Female rats (200 g body weight) were either untreated or given carbimazole (0.1 g/100 ml) in their drinking water for up to 12 weeks. The mitotic rate of the thyroid follicular cells was estimated using vincristine sulphate. Measurement of whole-body oxygen consumption showed that the rats were clearly hypothyroid after 1 week of treatment. The mitotic rate rose rapidly from the control value of 3.65% metaphases/day to about 25%/day after 4 days and was maintained at this level for at least 5 weeks of treatment. The changes in mitotic rate were apparently synchronous with the histological changes. The results of earlier studies are reviewed and discussed in relation to recent concepts of cell populations. PMID:721696

Redmond, O; Tuffery, A R

1978-01-01

345

Moscatilin Induces Apoptosis and Mitotic Catastrophe in Human Esophageal Cancer Cells  

PubMed Central

Abstract Moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii, has been shown to possess anticancer activity. We examined the effect of moscatilin on human esophageal cancer cells, including squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cells and its possible mechanisms. Moscatilin suppressed the growth of both the histological cell lines in a dose- and time-dependent manner. Morphological changes indicative of apoptosis and mitotic catastrophe were observed following moscatilin treatment. The population of cells in the sub-G1 phase and polyploidy phase significantly increased after treatment. Immunofluorescence revealed multipolar mitosis and subsequent multinucleation in moscatilin-treated cells, indicating the development of mitotic catastrophe. Western blot showed a marked increase in expressions of polo-like kinase 1 and cyclin B1 after exposure to moscatilin. In conclusion, moscatilin inhibits growth and induces apoptosis and mitotic catastrophe in human esophageal SCC- and ADC-derived cell lines, indicating that moscatilin has broad potential against esophageal cancer. PMID:24074296

Chen, Chien-An; Chen, Chien-Chih; Shen, Chien-Chang

2013-01-01

346

Moscatilin induces apoptosis and mitotic catastrophe in human esophageal cancer cells.  

PubMed

Moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii, has been shown to possess anticancer activity. We examined the effect of moscatilin on human esophageal cancer cells, including squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cells and its possible mechanisms. Moscatilin suppressed the growth of both the histological cell lines in a dose- and time-dependent manner. Morphological changes indicative of apoptosis and mitotic catastrophe were observed following moscatilin treatment. The population of cells in the sub-G1 phase and polyploidy phase significantly increased after treatment. Immunofluorescence revealed multipolar mitosis and subsequent multinucleation in moscatilin-treated cells, indicating the development of mitotic catastrophe. Western blot showed a marked increase in expressions of polo-like kinase 1 and cyclin B1 after exposure to moscatilin. In conclusion, moscatilin inhibits growth and induces apoptosis and mitotic catastrophe in human esophageal SCC- and ADC-derived cell lines, indicating that moscatilin has broad potential against esophageal cancer. PMID:24074296

Chen, Chien-An; Chen, Chien-Chih; Shen, Chien-Chang; Chang, Hen-Hong; Chen, Yu-Jen

2013-10-01

347

The post-mitotic state in neurons correlates with a stable nuclear higher-order structure.  

PubMed

Neurons become terminally differentiated (TD) post-mitotic cells very early during development yet they may remain alive and functional for decades. TD neurons preserve the molecular machinery necessary for DNA synthesis that may be reactivated by different stimuli but they never complete a successful mitosis. The non-reversible nature of the post-mitotic state in neurons suggests a non-genetic basis for it since no set of mutations has been able to revert it. Comparative studies of the nuclear higher-order structure in neurons and cells with proliferating potential suggest that the non-reversible nature of the post-mitotic state in neurons has a structural basis in the stability of the nuclear higher-order structure. PMID:22808316

Aranda-Anzaldo, Armando

2012-03-01

348

Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase II?.  

PubMed

Mitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic "X" shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, KIF4 and condensin were mutually dependent for their dynamic localization on the chromatid axes. Depletion of either caused sister chromatids to expand and compromised the "intrinsic structure" of the chromosomes (defined in an in vitro assay), with loss of condensin showing stronger effects. Simultaneous depletion of KIF4 and condensin caused complete loss of chromosome morphology. In these experiments, topoisomerase II? contributed to shaping mitotic chromosomes by promoting the shortening of the chromatid axes and apparently acting in opposition to the actions of KIF4 and condensins. These three proteins are major determinants in shaping the characteristic mitotic chromosome morphology. PMID:23166350

Samejima, Kumiko; Samejima, Itaru; Vagnarelli, Paola; Ogawa, Hiromi; Vargiu, Giulia; Kelly, David A; de Lima Alves, Flavia; Kerr, Alastair; Green, Lydia C; Hudson, Damien F; Ohta, Shinya; Cooke, Carol A; Farr, Christine J; Rappsilber, Juri; Earnshaw, William C

2012-11-26

349

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

PubMed

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

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

2014-11-01

350

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

PubMed Central

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

Castellano-Pozo, Maikel; Garcia-Muse, Tatiana; Aguilera, Andres

2012-01-01

351

[Mitotic cycle in cell cultures infected with oncogenic type-12 adenoviruses].  

PubMed

Oncogenic adenovirus of type 12 in the culture of rat embryo fibroblasts, in which it induces an abortive infection, and in HEp-2 culture, whereas it shows reproduction and causes lytic infection, in the early stationary phase causes shortening of the mitotic cycle and its separate periods. Reduction of the mitotic cycle duration occurs on account of shortening of the presynthetic stage and DNA synthesis stage. This property of the virus is in agreement with its capacity to stimulate proliferation of infected cells and is likely to be one of the necessary conditions for development of malignant transformation. PMID:1274264

Ageenko, A I; Kogan, I Ia

1976-01-01

352

HMBA depolymerizes microtubules, activates mitotic checkpoints and induces mitotic block in MCF7 cells by binding at the colchicine site in tubulin  

Microsoft Academic Search

10-[(3-Hydroxy-4-methoxybenzylidene)]-9(10H)-anthracenone (HMBA), a synthetic compound, has been reported to have a potent antitumor activity. In this study, we found that HMBA depolymerized microtubules in MCF-7 cells and produced aberrant spindles in the MCF-7 cells. It also reduced the distance between the centrosomes and activated the mitotic checkpoint proteins BubR1 and Mad2. Further, HMBA inhibited the progression of MCF-7 cells in

Biswa Prasun Chatterji; Mithu Banerjee; Parminder Singh; Dulal Panda

2010-01-01

353

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

SciTech Connect

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.

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

354

Some distinctive features in the behavior of small-scale artificial ionospheric irregularities at mid-and high latitudes  

NASA Astrophysics Data System (ADS)

We present the results of experimental studies of some features in the behavior of small-scale artificial irregularities (SSAIs) at mid-and high latitudes based on the “Sura” and EISCAT/HEATING HF facilities. Observations were performed by the method of aspect scattering using a network of diagnostic paths having a common reception point located near St. Petersburg. We found that an extremely long duration of the second (slow) stage of SSAI relaxation of up to 5 min occurs in the evening hours when the ionosphere above the “Sura” facility is illuminated by the Sun, but the solar terminator travels through the magnetically conjugated ionosphere. The conjecture is made that the processes initiated by the terminator are mostly responsible for secondary ionospheric turbulence maintaining the irregularities above “Sura.” A drastic increase in the Doppler spectra width of the scattered signals is revealed when the magnetically conjugate point of the ionosphere is located on the shade side of the terminator, but the ionosphere above the “Sura” facility is still lighted. It is assumed that the “ run away” of photoelectrons from the day to the night side could reduce the threshold of excitation of artificial irregularities, leading to an increase in their intensity. The presence of fairly intense scattered signals was detected from the “Sura” and EISCAT/HEATING experimental results both under conditions of pulsed HF heating after continuous heater-on periods and cycled HF heating by short pulses. In the case of pulsed heating by short pulses with duration ?p < 100 ms and average radiated power Pa below the threshold power Pthr of the SSAI generation cutoff the irregularities can be maintained due only to striction parametric instabilities. The excitation of irregularites under the cycled HF pumping with the pulse duration ?p = 384 ms for Pa comparable with Pthr was detected. The aspect-angle dependence, or the so-called magnetic zenith effect, was found in the SSAI intensity. The residual turbulence aftereffects played a significant role in the SSAI development.

Blagoveshchenskaya, N. F.; Borisova, T. D.; Kornienko, V. A.; Frolov, V. L.; Rietveld, M. T.; Brekke, A.

2007-08-01

355

Chromosome no. 1 of Crepis capillaris shows dened 3D-shapes in mitotic A. B. Houtsmuller1  

E-print Network

Chromosome no. 1 of Crepis capillaris shows de®ned 3D-shapes in mitotic prophase A. B. Houtsmuller1, plant chromosome, prophase chromosome shape Abstract The shape of mitotic prophase chromosomes has been studied in root tip nuclei by confocal microscopy and 3D- image analysis. Crepis capillaris chromosome no

Smeulders, Arnold

356

Induction of Cellular DNA Synthesis and Increased Mitotic Activity in Syrian Hamster Embryo Cells Abortively Infected with Human Cytomegalovirus  

Microsoft Academic Search

SUMMARY The effect of human cytomegalovirus (CMV) on cell DNA synthesis and mitotic activity in hamster embryo fibroblasts was examined. The results indicated that CMV infected cells had increased rates of cell DNA replication and mitotic activity. Detection of the effect of CMV on these two parameters necessitated arrest of cells prior to infection with low serum concentrations. This lowered

T. Albrecht; M. Nachtigal; S. C. St Jeor; F. Rapp

1976-01-01

357

Unsupervised Linear Feature-Extraction Methods and Their Effects in the Classification of High-Dimensional Data  

Microsoft Academic Search

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

Luis O. Jimenez-Rodriguez; Emmanuel Arzuaga-Cruz; Miguel Velez-Reyes

2007-01-01

358

High-speed, full 3D feature metrology for litho monitoring, matching, and model calibration with scatterometry  

NASA Astrophysics Data System (ADS)

We studied the potential of optical scatterometry to measure the full 3D profile of features representative to real circuit design topology. The features were selected and printed under conditions to improve the measurability of the features by scatterometry without any loss of information content for litho monitoring and control applications. The impact of the scatterometry recipe and settings was evaluated and optimal settings were determined. We have applied this strategy on a variety of structures and gathered results using the YieldStar angular reflection based scatterometer. The reported results show that we obtained effective decoupling of the measurement of the 3 dimensions of the features. The results match with predictions by calibrated lithographic simulations. As a verification we have successfully performed a scanner matching experiment using computational Pattern Matcher (cPM) in combination with YieldStar as a metrology tool to characterize the difference between the scanners and verify the matching. The results thus obtained were better than using CD-SEM for matching and verification.

Cramer, Hugo; Chen, Alek; Li, Fahong; Leray, Philippe; Charley, Anne-Laure; van Look, Lieve; Bekaert, Joost; Cheng, Shaunee

2012-03-01

359

Use of Salient Features for the Design of a Multistage Framework to Extract Roads From High-Resolution Multispectral Satellite Images  

Microsoft Academic Search

The process of road extraction from high-resolution satellite images is complex, and most researchers have shown results on a few selected set of images. Based on the satellite data acquisition sensor and geolocation of the region, the type of processing varies and users tune several heuristic parame- ters to achieve a reasonable degree of accuracy. We exploit two salient features

Sukhendu Das; T. T. Mirnalinee; Koshy Varghese

2011-01-01

360

Techno-economic analysis of a wind–solar hybrid renewable energy system with rainwater collection feature for urban high-rise application  

Microsoft Academic Search

The technical and economic feasibility study of an innovative wind–solar hybrid renewable energy generation system with rainwater collection feature for electrical energy generation is presented in this paper. The power generated would supply part of the energy requirements of the high-rise building where the system is installed. The system integrates and optimizes several green technologies; including urban wind turbine, solar

W. T. Chong; M. S. Naghavi; S. C. Poh; T. M. I. Mahlia; K. C. Pan

2011-01-01

361

Multi-Kinase Inhibitor C1 Triggers Mitotic Catastrophe of Glioma Stem Cells Mainly through MELK Kinase Inhibition  

PubMed Central

Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as a therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Previously, we identified that the mitotic kinase maternal embryonic leucine-zipper kinase (MELK) is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients. In addition, patient-derived GSCs depend on MELK for their survival and growth both in vitro and in vivo. Here, we demonstrate evidence that the role of MELK in the GSC survival is specifically dependent on its kinase activity. With in silico structure-based analysis for protein-compound interaction, we identified the small molecule Compound 1 (C1) is predicted to bind to the kinase-active site of MELK protein. Elimination of MELK kinase activity was confirmed by in vitro kinase assay in nano-molar concentrations. When patient-derived GSCs were treated with C1, they underwent mitotic arrest and subsequent cellular apoptosis in vitro, a phenotype identical to that observed with shRNA-mediated MELK knockdown. In addition, C1 treatment strongly induced tumor cell apoptosis in slice cultures of GBM surgical specimens and attenuated growth of mouse intracranial tumors derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes GSCs to radiation treatment. Collectively, these data indicate that targeting MELK kinase activity is a promising approach to attenuate GBM growth by eliminating GSCs in tumors. PMID:24739874

Joshi, Kaushal; Nakano-Okuno, Mariko; Hong, Christopher; Nguyen, Chi-Hung; Kornblum, Harley I.; Molla, Annie; Nakano, Ichiro

2014-01-01

362

Radiation-induced mitotic cell death and glioblastoma radioresistance: a new regulating pathway controlled by integrin-linked kinase, hypoxia-inducible factor 1 alpha and survivin in U87 cells.  

PubMed

We have previously shown that integrin-linked kinase (ILK) regulates U87 glioblastoma cell radioresistance by modulating the main radiation-induced cell death mechanism in solid tumours, the mitotic cell death. To decipher the biological pathways involved in these mechanisms, we constructed a U87 glioblastoma cell model expressing an inducible shRNA directed against ILK (U87shILK). We then demonstrated that silencing ILK enhanced radiation-induced centrosome overduplication, leading to radiation-induced mitotic cell death. In this model, ionising radiations induce hypoxia-inducible factor 1 alpha (HIF-1?) stabilisation which is inhibited by silencing ILK. Moreover, silencing HIF-1? in U87 cells reduced the surviving fraction after 2 Gy irradiation by increasing cell sensitivity to radiation-induced mitotic cell death and centrosome amplification. Because it is known that HIF-1? controls survivin expression, we then looked at the ILK silencing effect on survivin expression. We show that survivin expression is decreased in U87shILK cells. Furthermore, treating U87 cells with the specific survivin suppressor YM155 significantly increased the percentage of giant multinucleated cells, centrosomal overduplication and thus U87 cell radiosensitivity. In consequence, we decipher here a new pathway of glioma radioresistance via the regulation of radiation-induced centrosome duplication and therefore mitotic cell death by ILK, HIF-1? and survivin. This work identifies new targets in glioblastoma with the intention of radiosensitising these highly radioresistant tumours. PMID:23747271

Lanvin, Olivia; Monferran, Sylvie; Delmas, Caroline; Couderc, Bettina; Toulas, Christine; Cohen-Jonathan-Moyal, Elizabeth

2013-09-01

363

Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA).  

PubMed

Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis. PMID:24309115

Seo, Jae Sung; Kim, Ha Na; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Ki Sa; Yoon, Hyun-Joo; Yoo, Hae Yong; Choi, Cheol Yong

2014-01-01

364

RanGTP and CLASP1 cooperate to position the mitotic spindle.  

PubMed

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

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

2013-08-01

365

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

PubMed

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

Clark, M S; Parker, J S

1992-09-01

366

Mutations that increase the mitotic stability of minichromosomes in yeast: Characterization of RAR1  

Microsoft Academic Search

In an attempt to identify proteins involved in the initiation of DNA replication, we have isolated a series of Saccharomyces cerevisiae mutants in which the function of putative replication origins is affected. The phenotype of these Rar- (regulation of autonomous replication) mutants is to increase the mitotic stability of plasmids whose replication is dependent on weak ARS elements. These mutations

Stephen E. Kearsey; Jeanette Edwards

1987-01-01

367

Chlamydia trachomatis infection causes mitotic spindle pole defects independently from its effects on centrosome amplification  

PubMed Central

Chlamydiae are gram negative, obligate intracellular bacteria, and Chlamydia trachomatis is the etiologic agent of the most commonly reported sexually transmitted disease in the United States. Chlamydiae undergo a biphasic life cycle that takes place inside a parasitophorous vacuole termed an inclusion. Chlamydial infections have been epidemiologically linked to cervical cancer in patients previously infected by human papillomavirus (HPV). The inclusion associates very closely with host cell centrosomes, and this association is dependent upon the host motor protein dynein. We have previously reported that this interaction induces supernumerary centrosomes in infected cells, leading to multipolar mitotic spindles and inhibiting accurate chromosome segregation. Our findings demonstrate that chlamydial infection causes mitotic spindle defects independently of its effect on centrosome amplification. We show that chlamydial infection increases centrosome spread and inhibits the spindle assembly checkpoint delay to disrupt centrosome clustering. These data suggest chlamydial infection exacerbates the consequences of centrosome amplification by inhibiting the cells’ ability to suppress the effects of these defects on mitotic spindle organization. We hypothesize that these combined effects on mitotic spindle architecture identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation. PMID:21477082

Knowlton, Andrea E.; Brown, Heather M.; Richards, Theresa S.; Andreolas, Lauren A.; Patel, Rahul K.; Grieshaber, Scott S.

2011-01-01

368

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

E-print Network

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 ...

Coughlin, M.

369

Isolation of Human Mitotic Protein Phosphatase Complexes: Identification of a Complex between Protein  

E-print Network

Nimick1 , Laura Trinkle-Mulcahy2 , Robert Gourlay3 , Nick Morrice3¤ , Greg B. G. Moorhead1 * 1 Department Wever V, Lloyd DC, Nasa I, Nimick M, Trinkle-Mulcahy L, et al. (2012) Isolation of Human Mitotic Protein

Trinkle-Mulcahy, Laura

370

Dynamic Phosphorylation of HP1? Regulates Mitotic Progression in Human Cells  

PubMed Central

Heterochromatin protein 1? (HP1?), a key player in the establishment and maintenance of higher-order chromatin regulates key cellular processes, including metaphase chromatid cohesion and centromere organization. However, how HP1? controls these processes is not well understood. Here we demonstrate that post-translational modifications of HP1? dictate its mitotic functions. HP1? is constitutively phosphorylated within its N-terminus whereas phosphorylation within the hinge domain occurs preferentially at G2/M phase of the cell cycle. The hinge-phosphorylated form of HP1? specifically localizes to kinetochores during early mitosis and this phosphorylation mediated by NDR1 kinase is required for mitotic progression and for Sgo1 binding to mitotic centromeres. Cells lacking NDR kinase show loss of mitosis-specific phosphorylation of HP1? leading to prometaphase arrest. Our results reveal that NDR kinase catalyzes the hinge-specific phosphorylation of human HP1? during G2/M in vivo and this orchestrates accurate chromosome alignment and mitotic progression. PMID:24619172

Chakraborty, Arindam; Prasanth, Kannanganattu V.; Prasanth, Supriya G.

2014-01-01

371

Mediation of meiotic and early mitotic chromosome segregation in Drosophila by a protein related to kinesin  

Microsoft Academic Search

CONTRARY to the traditional view that microtubules pull chromosomes polewards during the anaphase stage of meiotic and mitotic cell divisions, new evidence suggests that the chromosome movements are driven by a motor located at the kinetochore1-3. The process of chromosome segregation involves proper arrangement of kinetochores for spindle attachment, followed by spindle attachment and chromosome movement. Mechanisms in Drosophila for

Sharyn A. Endow; Steven Henikoff; Linda Soler-Niedziela

1990-01-01

372

O-linked N-acetylglucosamine cycling regulates mitotic spindle organization.  

PubMed

Any defects in the correct formation of the mitotic spindle will lead to chromosomal segregation errors, mitotic arrest, or aneuploidy. We demonstrate that O-linked N-acetylglucosamine (O-GlcNAc), a post-translational modification of serine and threonine residues in nuclear and cytoplasmic proteins, regulates spindle function. In O-GlcNAc transferase or O-GlcNAcase gain of function cells, the mitotic spindle is incorrectly assembled. Chromosome condensation and centrosome assembly is impaired in these cells. The disruption in spindle architecture is due to a reduction in histone H3 phosphorylation by Aurora kinase B. However, gain of function cells treated with the O-GlcNAcase inhibitor Thiamet-G restored the assembly of the spindle and partially rescued histone phosphorylation. Together, these data suggest that the coordinated addition and removal of O-GlcNAc, termed O-GlcNAc cycling, regulates mitotic spindle organization and provides a potential new perspective on how O-GlcNAc regulates cellular events. PMID:23946484

Tan, Ee Phie; Caro, Sarah; Potnis, Anish; Lanza, Christopher; Slawson, Chad

2013-09-20

373

O-Linked N-Acetylglucosamine Cycling Regulates Mitotic Spindle Organization*  

PubMed Central

Any defects in the correct formation of the mitotic spindle will lead to chromosomal segregation errors, mitotic arrest, or aneuploidy. We demonstrate that O-linked N-acetylglucosamine (O-GlcNAc), a post-translational modification of serine and threonine residues in nuclear and cytoplasmic proteins, regulates spindle function. In O-GlcNAc transferase or O-GlcNAcase gain of function cells, the mitotic spindle is incorrectly assembled. Chromosome condensation and centrosome assembly is impaired in these cells. The disruption in spindle architecture is due to a reduction in histone H3 phosphorylation by Aurora kinase B. However, gain of function cells treated with the O-GlcNAcase inhibitor Thiamet-G restored the assembly of the spindle and partially rescued histone phosphorylation. Together, these data suggest that the coordinated addition and removal of O-GlcNAc, termed O-GlcNAc cycling, regulates mitotic spindle organization and provides a potential new perspective on how O-GlcNAc regulates cellular events. PMID:23946484

Tan, Ee Phie; Caro, Sarah; Potnis, Anish; Lanza, Christopher; Slawson, Chad

2013-01-01

374

Mitotic Histone H3 Phosphorylation by Vaccinia-Related Kinase 1 in Mammalian Cells? †  

PubMed Central

Mitotic chromatin condensation is essential for cell division in eukaryotes. Posttranslational modification of the N-terminal tail of histone proteins, particularly by phosphorylation by mitotic histone kinases, may facilitate this process. In mammals, aurora B is believed to be the mitotic histone H3 Ser10 kinase; however, it is not sufficient to phosphorylate H3 Ser10 with aurora B alone. We show that histone H3 is phosphorylated by vaccinia-related kinase 1 (VRK1). Direct phosphorylation of Thr3 and Ser10 in H3 by VRK1 both in vitro and in vivo was observed. Loss of VRK1 activity was associated with a marked decrease in H3 phosphorylation during mitosis. Phosphorylation of Ser10 by VRK1 is similar to that by aurora B. Moreover, expression and chromatin localization of VRK1 depended on the cell cycle phase. Overexpression of VRK1 resulted in a dramatic condensation of nuclei. Our findings collectively support a role of VRK1 as a novel mitotic histone H3 kinase in mammals. PMID:17938195

Kang, Tae-Hong; Park, Do-Young; Choi, Yoon Ha; Kim, Kyung-Jin; Yoon, Ho Sup; Kim, Kyong-Tai

2007-01-01

375

Regulation of mitotic cytoskeleton dynamics and cytokinesis by integrin-linked kinase in retinoblastoma cells.  

PubMed

During cell division integrin-linked kinase (ILK) has been shown to regulate microtubule dynamics and centrosome clustering, processes involved in cell cycle progression, and malignant transformation. In this study, we examine the effects of downregulating ILK on mitotic function in human retinoblastoma cell lines. These retinal cancer cells, caused by the loss of function of two gene alleles (Rb1) that encode the retinoblastoma tumour suppressor, have elevated expression of ILK. Here we show that inhibition of ILK activity results in a concentration-dependent increase in nuclear area and multinucleated cells. Moreover, inhibition of ILK activity and expression increased the accumulation of multinucleated cells over time. In these cells, aberrant cytokinesis and karyokinesis correlate with altered mitotic spindle organization, decreased levels of cortical F-actin and centrosome de-clustering. Centrosome de-clustering, induced by ILK siRNA, was rescued in FLAG-ILK expressing Y79 cells as compared to those expressing FLAG-tag alone. Inhibition of ILK increased the proportion of cells exhibiting mitotic spindles and caused a significant G2/M arrest as early as 24 hours after exposure to QLT-0267. Live cell analysis indicate ILK downregulation causes an increase in multipolar anaphases and failed cytokinesis (bipolar and multipolar) of viable cells. These studies extend those indicating a critical function for ILK in mitotic cytoskeletal organization and describe a novel role for ILK in cytokinesis of Rb deficient cells. PMID:24911651

Sikkema, William K A; Strikwerda, Arend; Sharma, Manju; Assi, Kiran; Salh, Baljinder; Cox, Michael E; Mills, Julia

2014-01-01

376

Karyotype and C-Banding Patterns of Mitotic Chromosomes in Diploid Bromegrass (Bromus riparius Rehm)  

E-print Network

that it could be a progenitor ofhomologous chromosomes were paired and assigned numbers I to the Bromus inermisKaryotype and C-Banding Patterns of Mitotic Chromosomes in Diploid Bromegrass (Bromus riparius Rehm of the genus Bromus L. were limited 1988; Tayyar et al., 1994; Falistocco et al., 1995). Theto chromosome

Gill, Kulvinder

377

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

E-print Network

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...

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

2005-12-01

378

WT1 interacts with MAD2 and regulates mitotic checkpoint function.  

PubMed

Tumour 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 tumour 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, RNA interference-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

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

2014-01-01

379

Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase , Satoru Inaba1  

E-print Network

Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1 Anu Gupta1 University, Stanford, CA 94305, USA The abnormal expression of breast cancer-specific gene 1 (BCSG1 that BCSG1 expression significantly stimulates proliferation, invasion, and metastasis of breast cancer

Fang, Guowei

380

Frequencies of mutagen-induced coincident mitotic recombination at unlinked loci in Saccharomyces cerevisiae.  

PubMed

Frequencies of coincident genetic events were measured in strain D7 of Saccharomyces cerevisiae. This diploid strain permits the detection of mitotic gene conversion involving the trp5-12 and trp5-27 alleles, mitotic crossing-over and gene conversion leading to the expression of the ade2-40 and ade2-119 alleles as red and pink colonies, and reversion of the ilv1-92 allele. The three genes are on different chromosomes, and one might expect that coincident (simultaneous) genetic alterations at two loci would occur at frequencies predicted by those of the single alterations acting as independent events. Contrary to this expectation, we observed that ade2 recombinants induced by bleomycin, beta-propiolactone, and ultraviolet radiation occur more frequently among trp5 convertants than among total colonies. This excess among trp5 recombinants indicates that double recombinants are more common than expected for independent events. No similar enrichment was found among Ilv(+) revertants. The possibility of an artifact in which haploid yeasts that mimic mitotic recombinants are generated by a low frequency of cryptic meiosis has been excluded. Several hypotheses that can explain the elevated incidence of coincident mitotic recombination have been evaluated, but the cause remains uncertain. Most evidence suggests that the excess is ascribable to a subset of the population being in a recombination-prone state. PMID:17156798

Freeman, Kathryn M; Hoffmann, George R

2007-03-01

381

Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals  

PubMed Central

Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B–Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB. PMID:24101512

Álvarez-Fernández, Mónica; Sánchez-Martínez, Ruth; Sanz-Castillo, Belén; Gan, Pei Pei; Sanz-Flores, María; Trakala, Marianna; Ruiz-Torres, Miguel; Lorca, Thierry; Castro, Anna; Malumbres, Marcos

2013-01-01

382

Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.  

PubMed

Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B-Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB. PMID:24101512

Álvarez-Fernández, Mónica; Sánchez-Martínez, Ruth; Sanz-Castillo, Belén; Gan, Pei Pei; Sanz-Flores, María; Trakala, Marianna; Ruiz-Torres, Miguel; Lorca, Thierry; Castro, Anna; Malumbres, Marcos

2013-10-22

383

Mitotic progression becomes irreversible in prometaphase and collapses when Wee1 and Cdc25 are inhibited  

PubMed Central

Mitosis requires precise coordination of multiple global reorganizations of the nucleus and cytoplasm. Cyclin-dependent kinase 1 (Cdk1) is the primary upstream kinase that directs mitotic progression by phosphorylation of a large number of substrate proteins. Cdk1 activation reaches the peak level due to positive feedback mechanisms. By inhibiting Cdk chemically, we showed that, in prometaphase, when Cdk1 substrates approach the peak of their phosphorylation, cells become capable of proper M-to-G1 transition. We interfered with the molecular components of the Cdk1-activating feedback system through use of chemical inhibitors of Wee1 and Myt1 kinases and Cdc25 phosphatases. Inhibition of Wee1 and Myt1 at the end of the S phase led to rapid Cdk1 activation and morphologically normal mitotic entry, even in the absence of G2. Dampening Cdc25 phosphatases simultaneously with Wee1 and Myt1 inhibition prevented Cdk1/cyclin B kinase activation and full substrate phosphorylation and induced a mitotic “collapse,” a terminal state characterized by the dephosphorylation of mitotic substrates without cyclin B proteolysis. This was blocked by the PP1/PP2A phosphatase inhibitor, okadaic acid. These findings suggest that the positive feedback in Cdk activation serves to overcome the activity of Cdk-opposing phosphatases and thus sustains forward progression in mitosis. PMID:21325631

Potapova, Tamara A.; Sivakumar, Sushama; Flynn, Jennifer N.; Li, Rong; Gorbsky, Gary J.

2011-01-01

384

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

Microsoft Academic Search

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

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

1988-01-01

385

Mediator can regulate mitotic entry and direct periodic transcription in fission yeast.  

PubMed

Cdk8 is required for correct timing of mitotic progression in fission yeast. How the activity of Cdk8 is regulated is unclear, since the kinase is not activated by T-loop phosphorylation and its partner, CycC, does not oscillate. Cdk8 is, however, a component of the multiprotein Mediator complex, a conserved coregulator of eukaryotic transcription that is connected to a number of intracellular signaling pathways. We demonstrate here that other Mediator components regulate the activity of Cdk8 in vivo and thereby direct the timing of mitotic entry. Deletion of Mediator components Med12 and Med13 leads to higher cellular Cdk8 protein levels, premature phosphorylation of the Cdk8 target Fkh2, and earlier entry into mitosis. We also demonstrate that Mediator is recruited to clusters of mitotic genes in a periodic fashion and that the complex is required for the transcription of these genes. We suggest that Mediator functions as a hub for coordinated regulation of mitotic progression and cell cycle-dependent transcription. The many signaling pathways and activator proteins shown to function via Mediator may influence the timing of these cell cycle events. PMID:25154415

Banyai, Gabor; Lopez, Marcela Davila; Szilagyi, Zsolt; Gustafsson, Claes M

2014-11-01

386

An evaluation of techniques for the extraction of mineral absorption features from high spectral resolution remote sensing data  

NASA Technical Reports Server (NTRS)

Airborne Visible/Infrared Imaging Spectrometer data covering the wavelength range between 2000 and 2400 nm are examined for their ability to display the diagnostic mineral absorption features of certain alteration minerals, employing various data processing techniques. The techniques may be separated into two broad categories: scene based techniques that use parameters derived from the data themselves, and correction techniques utilizing external information such as solar/atmospheric models. Results indicate that the data corrected utilizing the LOWTRAN 7 atmospheric transfer code constrained with local weather station data are the most effective at showing the diagnostic absorption features of the regions of known mineralogy and introduce the least number of artifacts into the data.

Rast, Michael; Hook, Simon J.; Alley, Ronald E.; Elvidge, Christopher D.

1991-01-01

387

A 90nm high volume manufacturing logic technology featuring novel 45nm gate length strained silicon CMOS transistors  

Microsoft Academic Search

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

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

388

P2P-R protein localizes to the nucleolus of interphase cells and the periphery of chromosomes in mitotic cells which show maximum P2P-R immunoreactivity.  

PubMed

P2P-R is a nuclear protein that can bind both p53 and Rb1. Its functions include roles in the control of RNA metabolism, apoptosis, and p53-dependent transcription. The expression of P2P-R also is repressed in G1 arrested terminally differentiated cells. The current studies therefore evaluated if P2P-R undergoes cell cycle-associated changes in its abundance and/or localization. Western blots show that relative to G0 quiescent cells, P2P-R protein levels are higher in populations of G2/M cells prepared by the physiological parasynchronization technique of serum deprivation followed by serum stimulation. More striking is the > 10-fold enrichment of P2P-R protein in specimens of highly purified mitotic cells prepared by the mitotic shake-select technique, or by synchrony with the mitotic spindle disruption agents nocodazole or vinblastine. These changes in P2P-R protein occur without a concomitant change in P2P-R mRNA expression suggesting that P2P-R immunoreactivity increases during mitosis. Confocal microscopy next established the localization of P2P-R to nucleoli in interphase cells and at the periphery of chromosomes in mitotic cells that lack nucleoli. The high levels of P2P-R localized to the periphery of chromosomes in mitotic cells suggest that P2P-R shares characteristics with other nucleolar proteins that associate with the periphery of chromosomes during mitosis. These include: nucleolin, B23, Ki67, and fibrillarin. PMID:12064457

Gao, Sizhi; Witte, Michael M; Scott, Robert E

2002-05-01

389

Saccharomyces cerevisiae mutants with enhanced induced mutation and altered mitotic gene conversion.  

PubMed

We have developed a method to isolate yeast (Saccharomyces cerevisiae) mutants with enhanced induced mutagenesis based on nitrous acid-induced reversion of the ade2-42 allele. Six mutants have been isolated and designated him (high induced mutagenesis), and 4 of them were studied in more detail. The him mutants displayed enhanced reversion of the ade2-42 allele, either spontaneous or induced by nitrous acid, UV light, and the base analog 6-N-hydroxylaminopurine, but not by gamma-irradiation. It is worth noting that the him mutants turned out not to be sensitive to the lethal effects of the mutagens used. The enhancement in mutation induced by nitrous acid, UV light, and 6-N-hydroxylaminopurine has been confirmed in a forward-mutation assay (induction of mutations in the ADE1, ADE2 genes). The latter agent revealed the most apparent differences between the him mutants and the wild-type strain and was, therefore, chosen for the genetic analysis of mutants, him mutations analyzed behaved as a single Mendelian trait; complementation tests indicated 3 complementation groups (HIM1, HIM2, and HIM3), each containing 1 mutant allele. Uracil-DNA glycosylase activity was determined in crude cell extracts, and no significant differences between the wild-type and him strains were detected. Spontaneous mitotic gene conversion at the ADE2 locus is altered in him1 strains, either increased or decreased, depending on the particular heteroallelic combination. Genetic evidence strongly suggests him mutations to be involved in a process of mismatch correction of molecular heteroduplexes. PMID:2668746

Ivanov, E L; Kovaltzova, S V; Korolev, V G

1989-08-01

390

Mutation of the retinoblastoma tumor suppressor gene sensitizes cancers to mitotic inhibitor induced cell death  

PubMed Central

The retinoblastoma gene Rb is a prototype tumor suppressor, which encodes a protein that is inactivated in a broad range of human cancers through different mechanisms. Rb functions to regulate cell proliferation, differentiation, as well as cell death. Therefore, even though Rb inactivation promotes cancer development, this may also open up certain vulnerabilities of cancers that can potentially be targeted with drug intervention. Based on the assumption that cancers that have mutation, deletion, or rearrangement in the Rb locus represent strong loss of Rb function while cancers with WT Rb on average retain some Rb function, we searched Genomics of Drug Sensitivity in Cancer database to identify cancer drugs that are particularly effective to cancers with Rb genomic alterations. Three mitotic inhibitors were identified from this analysis. We further tested the effects of two mitotic inhibitors, Taxol and STLC, on prostate and breast cancer cells. We demonstrate that the Rb status affects cancer cell sensitivity to these mitotic drugs and that the sensitizing effects of Rb are mediated in part by its regulation of the cell cycle checkpoint protein Mad2. Since the mitotic inhibitors identified in our analysis inhibit mitosis through distinct targets, it is possible that the Rb functional status may serve as a general biomarker for cancer sensitivity to mitotic inhibitors. Because the Rb pathway is inactivated in a large number of human cancers, identification of agents that are particularly effective or ineffective based on the Rb status in cancers can potentially be used generally to matching patients with appropriate treatments to achieve better therapeutic outcome. PMID:24482737

Zhao, Jiong; Zhang, Zhenyu; Liao, Yang; Du, Wei

2014-01-01

391

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

NASA Technical Reports Server (NTRS)

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.

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

2002-01-01

392

Solitary fibrous tumors and hemangiopericytomas of the meninges: overlapping pathological features and common prognostic factors suggest the same spectrum of tumors.  

PubMed

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well-defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high-power fields, vasculo-nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features between SFT and HPC. The most relevant histological prognostic factors in the whole cohort for both progression-free survival (PFS) and overall survival (OS) in univariate analysis were hypercellularity, high mitotic count (>5 per 10 high-power fields) and necrosis. On the basis of these results, we propose a new grading scheme for these tumors which was of pronostic value for both PFS and OS in uni- and multivariate analysis. As extent of surgery was also a prognostic factor for both PFS and OS in univariate analysis, we propose that management of SFT/HPC might be based both on quality of removal and histological grade. PMID:22082190

Bouvier, Corinne; Métellus, Philippe; de Paula, André Maues; Vasiljevic, Alexandre; Jouvet, Anne; Guyotat, Jacques; Mokhtari, Karima; Varlet, Pascale; Dufour, Henry; Figarella-Branger, Dominique

2012-07-01

393

Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma  

PubMed Central

Background Medulloblastoma is the most common type of malignant brain tumor that afflicts children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients do poorly with significant morbidity. Methods To identify new molecular targets, we performed an integrated genomic analysis using structural and functional methods. Gene expression profiling in 16 medulloblastoma patient samples and subsequent gene set enrichment analysis indicated that cell cycle-related kinases were associated with disease development. In addition a kinome-wide small interfering RNA (siRNA) screen was performed to identify kinases that, when inhibited, could prevent cell proliferation. The two genome-scale analyses were combined to identify key vulnerabilities in medulloblastoma. The inhibition of one of the identified targets was further investigated using RNAi and a small molecule inhibitor. Results Combining the two analyses revealed that mitosis-related kinases were critical determinants of medulloblastoma cell proliferation. RNA interference (RNAi)-mediated knockdown of WEE1 kinase and other mitotic kinases was sufficient to reduce medulloblastoma cell proliferation. These data prompted us to examine the effects of inhibiting WEE1 by RNAi and by a small molecule inhibitor of WEE1, MK-1775, in medulloblastoma cell lines. MK-1775 inhibited the growth of medulloblastoma cell lines, induced apoptosis and increased DNA damage at nanomolar concentrations. Further, MK-1775 was synergistic with cisplatin in reducing medulloblastoma cell proliferation and resulted in an associated increase in cell death. In vivo MK-1775 suppressed medulloblastoma tumor growth as a single agent. Conclusions Taken together, these findings highlight mitotic kinases and, in particular, WEE1 as a rational therapeutic target for medulloblastoma. PMID:24661910

2014-01-01

394

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)

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 measuremen