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Extragnathic odontogenic sinonasal myxoma with mitotic features  

PubMed Central

We present the first-ever documented evidence of mitotic figures in a case of sinonasal myxoma diagnosed in a 37 year-old gentleman. A 37 year-old gentleman was referred to the Otolaryngology clinic with left nasal discharge for six months. Preoperative images demonstrated obstruction of the left nasal airway with complete opacification of the left maxillary sinus, obscuration of the osteomeatal complex, as well as expansion and thinning of the medial wall of the maxillary antrum. The patient underwent diagnostic Funtional Endoscopic Sinus Surgery (FESS), therapeutic left Caldwell-Luc antrostomy, and revision FESS following recurrence. The patient was symptom-free at routine follow-up post-op. There has been much debate as to whether the absence of mitotic features in a specimen is absolutely necessary in order to confirm the diagnosis. We postulate that the presence of mitoses is an unusual diagnostic feature in extensive sinonasal myxoma. PMID:24960748

Onyekwelu, O; DeZoysa, O; Watts, S



Visualizing the high curvature regions of post-mitotic nascent nuclear envelope membrane.  


We previously reported that mitotic endoplasmic reticulum (ER) membrane cisternae or sheets directly assemble mammalian nuclear envelope (NE) at the end of mitosis. In this study, we investigated the dynamics of the high curvature regions of partially assembled nuclear envelope membrane using reticulon4a as a probe. We found that, after sorting out reticulon4a from the nascent NE membrane sheets, reticulon4a is specifically localized to the leading edges. Our 3D time lapse images suggested that ER tubules could be incompetent in assembling the NE membrane. Our findings suggest a possible role of reticulons at the leading edges during the NE re-assembly and provide further evidences that the mitotic assembly of NE is by ER cisternae rather than tubules. PMID:22482003

Lu, Lei; Kirchhausen, Tomas



The human mitotic kinesin KIF18A binds protein phosphatase 1 (PP1) through a highly conserved docking motif.  


Protein phosphatase 1 (PP1), a serine/threonine protein phosphatase, controls diverse key cellular events. PP1 catalytic subunits form complexes with a variety of interacting proteins that control its ability to dephosphorylate substrates. Here we show that the human mitotic kinesin-8, KIF18A, directly interacts with PP1? through a conserved RVxF motif. Our phylogenetic analyses of the kinesins further uncovered the broad conservation of this interaction potential within the otherwise highly diverse motor-protein superfamily. This suggests an ancestral origin of PP1 recruitment to KIF18A and a strategic role in human mitotic cells. PMID:25281536

De Wever, Veerle; Nasa, Isha; Chamousset, Delphine; Lloyd, David; Nimick, Mhairi; Xu, Hui; Trinkle-Mulcahy, Laura; Moorhead, Greg B G



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.



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



The Drosophila Salivary Gland Chromocenter Contains Highly Polytenized Subdomains of Mitotic Heterochromatin  

PubMed Central

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

Zhang, P.; Spradling, A. C.



Induction of high mitotic index in Petunia suspension cultures by sequential treatment with aphidicolin and colchicine  

Microsoft Academic Search

Significantly higher than normal mitotic index (MI) values were induced in Petunia cell suspensions following treatments with colchicine, aphidicolin, drastic medium replacement, or a sequential application of aphidicolin and colchicine. This last treatment yielded the highest MI values: cells incubated with 30 µg\\/ml aphidicolin for 18 h, then cultured in drug-free medium for 8 h and finally exposed to 0.1%

Assaf Guri; Aaron Zelcer; Shamay Izhar



Temporal models for mitotic phase labelling.  


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

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



Condensin: Architect of mitotic chromosomes  

Microsoft Academic Search

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

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



Evidence of activity-specific, radial organization of mitotic chromosomes in Drosophila.  


The organization and the mechanisms of condensation of mitotic chromosomes remain unsolved despite many decades of efforts. The lack of resolution, tight compaction, and the absence of function-specific chromatin labels have been the key technical obstacles. The correlation between DNA sequence composition and its contribution to the chromosome-scale structure has been suggested before; it is unclear though if all DNA sequences equally participate in intra- or inter-chromatin or DNA-protein interactions that lead to formation of mitotic chromosomes and if their mitotic positions are reproduced radially. Using high-resolution fluorescence microscopy of live or minimally perturbed, fixed chromosomes in Drosophila embryonic cultures or tissues expressing MSL3-GFP fusion protein, we studied positioning of specific MSL3-binding sites. Actively transcribed, dosage compensated Drosophila genes are distributed along the euchromatic arm of the male X chromosome. Several novel features of mitotic chromosomes have been observed. MSL3-GFP is always found at the periphery of mitotic chromosomes, suggesting that active, dosage compensated genes are also found at the periphery of mitotic chromosomes. Furthermore, radial distribution of chromatin loci on mitotic chromosomes was found to be correlated with their functional activity as judged by core histone modifications. Histone modifications specific to active chromatin were found peripheral with respect to silent chromatin. MSL3-GFP-labeled chromatin loci become peripheral starting in late prophase. In early prophase, dosage compensated chromatin regions traverse the entire width of chromosomes. These findings suggest large-scale internal rearrangements within chromosomes during the prophase condensation step, arguing against consecutive coiling models. Our results suggest that the organization of mitotic chromosomes is reproducible not only longitudinally, as demonstrated by chromosome-specific banding patterns, but also radially. Specific MSL3-binding sites, the majority of which have been demonstrated earlier to be dosage compensated DNA sequences, located on the X chromosomes, and actively transcribed in interphase, are positioned at the periphery of mitotic chromosomes. This potentially describes a connection between the DNA/protein content of chromatin loci and their contribution to mitotic chromosome structure. Live high-resolution observations of consecutive condensation states in MSL3-GFP expressing cells could provide additional details regarding the condensation mechanisms. PMID:21264350

Strukov, Yuri G; Sural, Tûba H; Kuroda, Mitzi I; Sedat, John W



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



High mitotic activity of Polo-like kinase 1 is required for chromosome segregation and genomic integrity in human epithelial cells.  


Protein kinases play key roles in regulating human cell biology, but manifold substrates and functions make it difficult to understand mechanism. We tested whether we could dissect functions of a pleiotropic mitotic kinase, Polo-like kinase 1 (Plk1), via distinct thresholds of kinase activity. We accomplished this by titrating Plk1 activity in RPE1 human epithelial cells using chemical genetics and verifying results in additional lines. We found that distinct activity thresholds are required for known functions of Plk1 including (from low to high activity) bipolar spindle formation, timely mitotic entry, and formation of a cytokinesis cleavage furrow. Subtle losses in Plk1 activity impaired chromosome congression and produced severe anaphase dysfunction characterized by poor separation of chromosome masses. These two phenotypes were separable, suggesting that they stem from distinct phosphorylation events. Impaired chromosome segregation in anaphase was the most sensitive to modest loss in Plk1 activity. Mechanistically, it was associated with unpaired sister chromatids with stretched kinetochores, suggestive of merotelic attachments. The C-terminal Polo box domain of Plk1 was required for its anaphase function, although it was dispensable for forming a bipolar spindle. The ultimate effect of partial inhibition of Plk1 was the formation of micronuclei, an increase in tetraploid progeny, and senescence. These results demonstrate that different thresholds of Plk1 activity can elicit distinct phenotypes, illustrating a general method for separating pleiotropic functions of a protein kinase even when these are executed close in time. PMID:23105120

Lera, Robert F; Burkard, Mark E



Mitotic Functions of Kinesin-5  

PubMed Central

In all eukaryotic cells, molecular motor proteins play essential roles in spindle assembly and function. The homotetrameric kinesin-5 motors in particular generate outward forces that establish and maintain spindle bipolarity and contribute to microtubule flux. Cell cycle dependent phosphorylation of kinesin-5 motors regulates their localization to the mitotic spindle. Analysis of live cells further shows that kinesin-5 motors are highly dynamic in the spindle. Understanding the interactions of kinesin-5 motors with microtubules and other spindle proteins is likely to broaden the documented roles of kinesin-5 motors during cell division. PMID:20109572

Ferenz, Nick P.; Gable, Alyssa; Wadsworth, Pat



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.



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


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



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

PubMed Central

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

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



Isolation of human mitotic protein phosphatase complexes: identification of a complex between protein phosphatase 1 and the RNA helicase Ddx21.  


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

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




Microsoft Academic Search

The high quality level that high resolution satellite images have reached in the last years has proved that these images could be a useful data source for the production of orthophoto and different mapping products. To test the capabilities of high resolution imagery, a study has been implemented in Gölba?i near Ankara. 12 ground control points were revised and signalized

V. O. Ataka; M. O. Altan


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


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



The S. pombe “cytokinesis” NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment via Pom1/Wee1  

PubMed Central

Mitotic exit integrates the reversal of the phosphorylation events initiated by mitotic kinases with a controlled cytokinesis event that cleaves the cell in two. The Mitotic Exit Network (MEN) of budding yeast regulates both processes, while the fission yeast equivalent, the Septum Initiation Network (SIN), only controls the execution of cytokinesis. The components and architecture of the SIN and MEN are highly conserved1. It is currently assumed that the functions of the core SIN/MEN components are restricted to their characterised roles at the end of mitosis. We now show that the NDR kinase component of the fission yeast SIN, Sid2/Mob1, acts independently of the other known SIN components in G2 phase of the cell cycle to control the timing of mitotic commitment. Sid2/Mob1 promotes mitotic commitment by directly activating the NIMA related kinase Fin1. Fin1’s activation promotes its own destruction, thereby making Fin1 activation a transient feature of G2 phase. This spike of Fin1 activation modulates the activity of the Pom1/Cdr1/Cdr2 geometry network towards Wee1. PMID:22684255

Grallert, Agnes; Connolly, Yvonne; Smith, Duncan L.; Simanis, Viesturs; Hagan, Iain M.



High dimensional feature reduction via projection pursuit  

NASA Technical Reports Server (NTRS)

The recent development of more sophisticated remote sensing systems enables the measurement of radiation in many more spectral intervals than previously possible. An example of that technology is the AVIRIS system, which collects image data in 220 bands. As a result of this, new algorithms must be developed in order to analyze the more complex data effectively. Data in a high dimensional space presents a substantial challenge, since intuitive concepts valid in a 2-3 dimensional space to not necessarily apply in higher dimensional spaces. For example, high dimensional space is mostly empty. This results from the concentration of data in the corners of hypercubes. Other examples may be cited. Such observations suggest the need to project data to a subspace of a much lower dimension on a problem specific basis in such a manner that information is not lost. Projection Pursuit is a technique that will accomplish such a goal. Since it processes data in lower dimensions, it should avoid many of the difficulties of high dimensional spaces. In this paper, we begin the investigation of some of the properties of Projection Pursuit for this purpose.

Jimenez, Luis; Landgrebe, David



FE Features in Highly Obscured AGN  

NASA Technical Reports Server (NTRS)

This final report is a summary of the combined study of ASCA (Advanced Satellite for Cosmology and Astrophysics) observations of NGC 7582 with archival ROSAT HRI (High Resolution Imager) and PSPC (Position Sensitive Proportional Counter) data. These observations were important in that they established that X-ray emission in NGC 7582, the most narrow-line of NLXGs (narrow-line X-ray galaxies), is associated with an AGN (Active Galactic Nuclei). Thus implying that all NLXGs are obscured AGN, as has been hypothesized to explain the X-ray spectral background paradox.

Schachter, Jonathan F.



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



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 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


Microtubule dependency of p34cdc2 inactivation and mitotic exit in mammalian cells  

PubMed Central

The protein kinase inhibitor 2-aminopurine induces checkpoint override and mitotic exit in BHK cells which have been arrested in mitosis by inhibitors of microtubule function (Andreassen, P. R., and R. L. Margolis. 1991. J. Cell Sci. 100:299-310). Mitotic exit is monitored by loss of MPM-2 antigen, by the reformation of nuclei, and by the extinction of p34cdc2-dependent H1 kinase activity. 2-AP-induced inactivation of p34cdc2 and mitotic exit depend on the assembly state of microtubules. During mitotic arrest generated by the microtubule assembly inhibitor nocodazole, the rate of mitotic exit induced by 2-AP decreases proportionally with increasing nocodazole concentrations. At nocodazole concentrations of 0.12 microgram/ml or greater, 2-AP induces no apparent exit through 75 min of treatment. In contrast, 2-AP brings about a rapid exit (t1/2 = 20 min) from mitotic arrest by taxol, a drug which causes inappropriate overassembly of microtubules. In control mitotic cells, p34cdc2 localizes to kinetochores, centrosomes, and spindle microtubules. We find that efficient exit from mitosis occurs under conditions where p34cdc2 remains associated with centrosomal microtubules, suggesting it must be present on these microtubules in order to be inactivated. Mitotic slippage, the natural reentry of cells into G1 during prolonged mitotic block, is also microtubule dependent. At high nocodazole concentrations slippage is prevented and mitotic arrest approaches 100%. We conclude that essential components of the machinery for exit from mitosis are present on the mitotic spindle, and that normal mitotic exit thereby may be regulated by the microtubule assembly state. PMID:7962060



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.



Mitotic trafficking of silicon microparticles†  

PubMed Central

Multistage carriers were recently introduced by our laboratory, with the concurrent objectives of co-localized delivery of multiple therapeutic agents, the “theranostic” integration of bioactive moieties with imaging contrast, and the selective, potentially personalized bypassing of the multiplicity of biological barriers that adversely impact biodistribution of vascularly injected particulates. Mesoporous (“nanoporous”) silicon microparticles were selected as primary carriers in multi-stage devices, with targets including vascular endothelia at pathological lesions. The objective of this study was to evaluate biocompatibility of mesoporous silicon microparticles with endothelial cells using in vitro assays with an emphasis on microparticle compatibility with mitotic events. We observed that vascular endothelial cells, following internalization of silicon microparticles, maintain cellular integrity, as demonstrated by cellular morphology, viability and intact mitotic trafficking of vesicles bearing silicon microparticles. The presence of gold or iron oxide nanoparticles within the porous matrix did not alter the cellular uptake of particles or the viability of endothelial cells subsequent to engulfment of microparticles. Endothelial cells maintained basal levels of IL-6 and IL-8 release in the presence of silicon microparticles. This is the first study that demonstrates polarized, ordered partitioning of endosomes based on tracking microparticles. The finding that mitotic sorting of endosomes is unencumbered by the presence of nanoporous silicon microparticles advocates the use of silicon microparticles for biomedical applications. PMID:20644846

Serda, Rita E.; Ferrati, Silvia; Godin, Biana; Tasciotti, Ennio; Liu, XueWu



Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum.  


The endocycle is a modified cell cycle that lacks M phase. Endocycles are well known for enabling continued growth of post-mitotic tissues. By contrast, we discovered pre-mitotic endocycles in precursors of Drosophila rectal papillae (papillar cells). Unlike all known proliferative Drosophila adult precursors, papillar cells endocycle before dividing. Furthermore, unlike diploid mitotic divisions, these polyploid papillar divisions are frequently error prone, suggesting papillar structures may accumulate long-term aneuploidy. Here, we demonstrate an indispensable requirement for pre-mitotic endocycles during papillar development and also demonstrate that such cycles seed papillar aneuploidy. We find blocking pre-mitotic endocycles disrupts papillar morphogenesis and causes organismal lethality under high-salt dietary stress. We further show that pre-mitotic endocycles differ from post-mitotic endocycles, as we find only the M-phase-capable polyploid cells of the papillae and female germline can retain centrioles. In papillae, this centriole retention contributes to aneuploidy, as centrioles amplify during papillar endocycles, causing multipolar anaphase. Such aneuploidy is well tolerated in papillae, as it does not significantly impair cell viability, organ formation or organ function. Together, our results demonstrate that pre-mitotic endocycles can enable specific organ construction and are a mechanism that promotes highly tolerated aneuploidy. PMID:25142462

Schoenfelder, Kevin P; Montague, Ruth A; Paramore, Sarah V; Lennox, Ashley L; Mahowald, Anthony P; Fox, Donald T



How to be a mitotic chromosome  

Microsoft Academic Search

Proper mitotic chromosome structure is essential for faithful chromosome segregation. Mounting evidence suggests that mitotic\\u000a chromosome assembly is a progressive, dynamic process that requires topoisomerase II, condensins and cohesin and the activity\\u000a of several signalling molecules. Current results suggest how these different activities might interact to achieve the familiar\\u000a form of the mitotic chromosome.

Sandra C. Moser; Jason R. Swedlow



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.



Spectral feature design in high dimensional multispectral data  

NASA Technical Reports Server (NTRS)

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

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



The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly.  


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 copurifying 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 antimitotic 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



On generating cell exemplars for detection of mitotic cells in breast cancer histopathology images.  


Mitotic activity is one of the main criteria that pathologists use to decide the grade of the cancer. Computerised mitotic cell detection promises to bring efficiency and accuracy into the grading process. However, detection and classification of mitotic cells in breast cancer histopathology images is a challenging task because of the large intra-class variation in the visual appearance of mitotic cells in various stages of cell division life cycle. In this paper, we test the hypothesis that cells in histopathology images can be effectively represented using cell exemplars derived from sub-images of various kinds of cells in an image for the purposes of mitotic cell classification. We compare three methods for generating exemplar cells. The methods have been evaluated in terms of classification performance on the MITOS dataset. The experimental results demonstrate that eigencells combined with support vector machines produce reasonably high detection accuracy among all the methods. PMID:25570713

Aloraidi, Nada A; Sirinukunwattana, Korsuk; Khan, Adnan M; Rajpoot, Nasir M



Feature Selection with High-Dimensional Imbalanced Data  

Microsoft Academic Search

Feature selection is an important topic in data mining, especially for high dimensional datasets. Filtering techniques in particular have received much attention, but detailed comparisons of their performance is lacking. This work considers three filters using classifier performance metrics and six commonly-used filters. All nine filtering techniques are compared and contrasted using five different microarray expression datasets. In addition, given

Jason Van Hulse; Taghi M. Khoshgoftaar; Amri Napolitano; Randall Wald



High-level feature extraction in JPEG compressed domain  

NASA Astrophysics Data System (ADS)

Traditional feature extraction techniques like the KLT, Harris and Wavelet work only in the uncompressed domain. Hence an additional step of decompression is required before any of them could be applied. We propose a two-level technique for extracting high-level feature points directly from JPEG compressed images. At the first level, the Discrete Cosine Transform (DCT) blocks having high activity content are filtered using a variance measure. At the next level, a DCT block centered at every pixel present in the filtered block is constructed from the neighboring DCT blocks. Feature points are then selected by analyzing the AC coefficients of the DCT block centered about it. The proposed method is simple and efficient. The extracted feature points were found to be rich in information content, which could be used for image registration. The results of this technique showed almost the same amount of repeatability between two images with 60% to 70% overlap, when compared with techniques available in the uncompressed domain. The features thus extracted can directly be used to calculate the motion parameters between two images in the compressed domain.

Narayanan, C. K.; Prakash, M. C.; Prabhakara Rao, G. V.



The effects of high presentation levels on consonant feature transmission  

NASA Astrophysics Data System (ADS)

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

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



Feature extraction and classification algorithms for high dimensional data  

NASA Technical Reports Server (NTRS)

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

Lee, Chulhee; Landgrebe, David



Image registration in high-dimensional feature space  

NASA Astrophysics Data System (ADS)

Image registration is a difficult task especially when spurrious image intensity differences and spatial variations between the two images are present. To robustify image registration algorithms to such spurrious variations it can be useful to employ an image registration matching criteria on higher dimensional feature spaces. This paper will present an overviewof our recent work on image registration using high dimensional image features and entropic graph matching criteria. New entropic graph estimates of information divergence measures will be presented. We will demonstrate the advantage of our approach for ultrasound breast image registration.

Neemuchwala, Huzefa F.; Hero, Alfred O.



Microelasticity of Single Mitotic Chromosomes  

NASA Astrophysics Data System (ADS)

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

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



Mitotically active deep juvenile xanthogranuloma.  


Juvenile xanthogranuloma is a relatively rare cutaneous tumor of histiocytic origin, occurring mainly in neonates, children, and young people in the first 2 decades of life. An occurrence in adults is rare. Very rare is also a "deep" subcutaneous and intramuscular localization of this tumor that is called in such case as "deep juvenile xanthogranuloma." A very uncommon variant of this tumor is the so-called mitotically active xanthogranuloma, which was described in the literature only in a single case. We present an interesting case of the mitotically active intramuscular juvenile xanthogranuloma of the upper arm in a 28-year-old woman. Before surgical excision, the tumor was examined by fine-needle aspiration biopsy. A diagnosis of deep malignant melanoma or alveolar rhabdomyosarcoma was considered. One year after the total excision, the patient is free of disease. In the presented case, we emphasize cytologic-histologic correlation. In the differential diagnosis, we considered especially an atypical diffuse giant cell tumor of tendon sheaths and joints (extra-articular pigmented villonodular synovitis) and some rare types of soft tissue leiomyosarcoma, such as epitheloid leiomyosarcoma and leiomyosarcoma with prominent osteoclast-like giant cells. PMID:20123455

Koren, Jan; Matecek, Ludovit; Zamecnik, Michal



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.



Multifaceted folding in a foldamer featuring highly cooperative folds.  


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

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



NudC Deacetylation Regulates Mitotic Progression  

PubMed Central

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

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



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


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

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



Micromechanical studies of mitotic chromosomes M.G. POIRIER1  

E-print Network

. Nomenclature Symbol Name Value A persistence length (mitotic newt chromosome) 0.1 m B bending modulus (mitotic newt chromosome) 10)22 N m2 f0 force constant (mitotic newt chromosome) 10)9 N g fluid viscosity (water and cell culture media) 10)3 Pa s g¢ internal viscosity (mitotic newt chromosome) 100 Pa s k Boltzmann

Marko, John F.



Microsoft Academic Search

A new compound, Surflan TM (Surflan), for mitotic polyploidization in vitro in lily was tested and compared with the original compound 'oryzalin'. Surflan was effective for mitotic polyploidization of lilies. The optimal concentration of Surflan was 0.0075% for in vitro chromosome doubling. A low concentration (0.0025%) was still effective to produce polyploid plants, however, a high concentration (0.0125%) showed phytotoxicity

T. Takamura; K. B. Lim; J. M. Van Tuyl


Study of features of high intensity noise effects during spaceflight  

NASA Technical Reports Server (NTRS)

Experiments were performed to study the effect on man of high intensity noises whose frequency range, length and volume corresponded to the conditions of the active period of spaceflight. The effect of 125-126 and 114-116 db of noise on the auditory and motor analyzers, and also on the condition of the pulse and blood pressure of 24 subjects was studied in 105 experiments during exposure for 20 minutes. It was found that noise at 125-126 db during the given exposure time causes unfavorable reactions on the part of the above mentioned indices. It was concluded that there is no danger from noise at 114-116 db for 20 minutes, considering the demands and particular features of spaceflight.

Yuganov, Y. M.; Krylov, Y. V.; Kuznetsov, V. S.



Chromosome aberration analysis and the influence of mitotic delay after simulated partial-body exposure with high doses of sparsely and densely ionising radiation  

Microsoft Academic Search

The influence of high doses of sparsely and densely ionising radiation on the yield of aberrant human peripheral lymphocytes in simulated partial-body exposures was studied by investigating radiation-induced chromosome aberration frequencies, namely dicentric and centric ring chromosomes. Peripheral blood samples from two volunteers were irradiated with high doses of 200 kV X-rays or neutrons with a mean energy of E\\u000a n>=2.1 MeV

Anna Heimers; Hein Jürgen Brede; Ulrich Giesen; Wolfgang Hoffmann



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

PubMed Central

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

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



Robust linear regression model of Ki-67 for mitotic rate in gastrointestinal stromal tumors  

PubMed Central

Risk stratification of gastrointestinal stromal tumors (GISTs) by tumor size, lymph node and metastasis status is crucially affected by mitotic activity. To date, no studies have quantitatively compared mitotic activity in hematoxylin and eosin (H&E)-stained tissue sections with immunohistochemical markers, such as phosphohistone H3 (PHH3) and Ki-67. According to the TNM guidelines, the mitotic count on H&E sections and immunohistochemical PHH3-stained slides has been assessed per 50 high-power fields of 154 specimens of clinically documented GIST cases. The Ki-67-associated proliferation rate was evaluated on three digitalized hot spots using image analysis. The H&E-based mitotic rate was found to correlate significantly better with Ki-67-assessed proliferation activity than with PHH3-assessed proliferation activity (r=0.780; P<0.01). A linear regression model (analysis of variance; P<0.001) allowed reliable predictions of the H&E-associated mitoses based on the Ki-67 expression alone. Additionally, the Ki-67-associated proliferation revealed a higher and significant impact on the recurrence and metastasis rate of the GIST cases than by the classical H&E-based mitotic rate. The results of the present study indicated that the mitotic rate may be reliably and time-efficiently estimated by immunohistochemistry of Ki-67 using only three hot spots. PMID:24527082




An unmet actin requirement explains the mitotic inhibition of clathrin-mediated endocytosis  

PubMed Central

Clathrin-mediated endocytosis (CME) is the major internalisation route for many different receptor types in mammalian cells. CME is shut down during early mitosis, but the mechanism of this inhibition is unclear. In this study, we show that the mitotic shutdown is due to an unmet requirement for actin in CME. In mitotic cells, membrane tension is increased and this invokes a requirement for the actin cytoskeleton to assist the CME machinery to overcome the increased load. However, the actin cytoskeleton is engaged in the formation of a rigid cortex in mitotic cells and is therefore unavailable for deployment. We demonstrate that CME can be ‘restarted’ in mitotic cells despite high membrane tension, by allowing actin to engage in endocytosis. Mitotic phosphorylation of endocytic proteins is maintained in mitotic cells with restored CME, indicating that direct phosphorylation of the CME machinery does not account for shutdown. DOI: PMID:24550251

Kaur, Satdip; Fielding, Andrew B; Gassner, Gisela; Carter, Nicholas J; Royle, Stephen J



Radar-anomalous, high-altitude features on Venus  

NASA Technical Reports Server (NTRS)

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

Muhleman, Duane O.; Butler, Bryan J.



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

E-print Network

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

Sekelsky, Jeff



PubMed Central

A method for isolating the mitotic apparatus from dividing sea urchin eggs without the use of ethyl alcohol or of detergents is described. In the present method, the eggs are dispersed directly in a medium containing 1 M (to 1.15 M) sucrose, 0.15 M dithiodiglycol, and 0.001 M Versene at pH 6, releasing the visibly intact mitotic apparatus. The method is designed for studies of enzyme activities, lipid components, and the variables affecting the stability of the apparatus. PMID:13768661

Mazia, Daniel; Mitchison, J. M.; Medina, Heitor; Harris, Patricia



The Design of High-Level Features for Photo Quality Assessment  

Microsoft Academic Search

We propose a principled method for designing high level features forphoto quality assessment. Our resulting system can classify between high quality professional pho- tos and low quality snapshots. Instead of using the bag of low-level features approach, we first determine the per- ceptual factors that distinguish between professional photos and snapshots. Then, we design high level semantic features to measure

Yan Ke; Xiaoou Tang; Feng Jing



Mechanisms of Mitotic Spindle Disassembly and Positioning in Saccharomyces cerevisiae  

E-print Network

2: Mitotic spindle disassembly occurs via distinct subprocesses driven by the Anaphase-Promoting Complex, Aurora B kinase, and kinesin-2: Mitotic spindle disassembly occurs via distinct subprocesses driven by the Anaphase-Promoting Complex, Aurora B kinase, and kinesin-

Woodruff, Jeffrey Blake



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



Unusual features of the high light acclimation of Chromera velia.  


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



Mitotic Spindle Proteomics in Chinese Hamster Ovary Cells  

Microsoft Academic Search

Mitosis is a fundamental process in the development of all organisms. The mitotic spindle guides the cell through mitosis as it mediates the segregation of chromosomes, the orientation of the cleavage furrow, and the progression of cell division. Birth defects and tissue-specific cancers often result from abnormalities in mitotic events. Here, we report a proteomic study of the mitotic spindle

Mary Kate Bonner; Daniel S. Poole; Tao Xu; Ali Sarkeshik; John R. Yates; Ahna R. Skop; Ziyin Li



INTRODUCTION Mitotic metaphase chromosomes show sister chromatids  

E-print Network

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

Villefranche sur mer


High performance object detection by collaborative learning of Joint Ranking of Granules features  

Microsoft Academic Search

Object detection remains an important but challenging task in computer vision. We present a method that combines high accuracy with high efficiency. We adopt simplified forms of APCF features, which we term Joint Ranking of Granules (JRoG) features; the features consists of discrete values by uniting binary ranking results of pair-wise granules in the image. We propose a novel collaborative

Chang Huang; Ramakant Nevatia



UEC at TRECVID 2009 High Level Feature Task Zhiyuan Tang, Akitsugu Noguchi and Keiji Yanai  

E-print Network

UEC at TRECVID 2009 High Level Feature Task Zhiyuan Tang, Akitsugu Noguchi and Keiji Yanai-s,noguchi-a,yanai} Abstract In this paper, we describe our approach and re- sults for high-level feature extraction task (HLF) at TRECVID2009. This year, we focus on fusion of a number of features effectively. Color, local pattern

Yanai, Keiji


Leveraging High-level and Low-level Features for Multimedia Event Detection  

E-print Network

: · A collection of Interest points High-level features: · Outdoor, Person, Bike #12;Classical Fusion · Early;Our Fusion · Train a local classifier with low-level features to capture the general idea of a videoLeveraging High-level and Low-level Features for Multimedia Event Detection Lu Jiang, Alexander G

Shamos, Michael I.


Segregation of genomes in polyploid tumour cells following mitotic catastrophe.  


Following irradiation p53-function-deficient tumour cells undergo mitotic catastrophe and form endopolyploid cells. A small proportion of these segregates nuclei, and give rise to viable descendants. Here we studied this process in five tumour cell lines. After mitotic failure, tumour cells enter the endocycle and form mono-nucleated or multi-nucleated giant cells (MOGC and MNGC). MNGC arise from arrested anaphases, MOGC, from arrested metaphases. In both cases the individual genomes establish a radial pattern by links to a single microtubule organizing centre. Segregation of genomes is also ordered. MNGC present features of mitosis being resumed from late anaphase. In MOGC the sub-nuclei retain arrangement of stacked metaphase plates and are separated by folds of the nuclear envelope. Mitosis then resumes in sub-nuclei directly from metaphase. The data presented indicate that endopolyploid tumour cells preserve the integrity of individual genomes and can potentially re-initiate mitosis from the point at which it was interrupted. PMID:16314119

Erenpreisa, Jekaterina; Kalejs, M; Ianzini, F; Kosmacek, E A; Mackey, M A; Emzinsh, D; Cragg, M S; Ivanov, A; Illidge, T M



Polyoma small T antigen triggers cell death via mitotic catastrophe.  


Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis. Live-cell and immunofluorescence studies showed that the majority of the PyST expressing cells were arrested in prometaphase with almost no cells progressing beyond metaphase. These cells exhibited defects in chromosomal congression, sister chromatid cohesion and spindle positioning, thereby resulting in the activation of the spindle assembly checkpoint. Prolonged mitotic arrest then led to cell death via mitotic catastrophe. Cell cycle inhibitors that block cells in G1/S prevented PyST-induced death. PyST-induced cell death that occurs during M is not dependent on p53 status. These data suggested, and our results confirmed, that PP2A inhibition could be used to preferentially kill cancer cells with p53 mutations that proliferate normally in the presence of cell cycle inhibitors.Oncogene advance online publication, 7 July 2014; doi:10.1038/onc.2014.192. PMID:24998850

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



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


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



Sodium azide induces mitotic recombination in Drosophila melanogaster larvae  

Microsoft Academic Search

Sodium azide (NaN3), a potent mutagen for bacteria and barley, was tested for somatic mutation and mitotic recombination induction in wing imaginal disc cells of Drosophila melanogaster. Comparisons were made among inversion-free flr3\\/mwh, inversion-heterozygous TM3, Ser\\/mwh, and inversion-free, high bioactivation OR(R), flr3\\/mwh flies. Third instar larvae were exposed chronically for 48 h to sodium azide at 0.5, 0.63. 0.75, 0.88

Edna González-César; Patricia Ramos-Morales



Caspase-3-dependent mitotic checkpoint inactivation by the small-molecule inducers of mitotic slippage SU6656 and geraldol.  


Microtubule-targeting cancer drugs such as paclitaxel block cell-cycle progression at mitosis by prolonged activation of the mitotic checkpoint. Cells can spontaneously escape mitotic arrest and enter interphase without chromosome segregation by a process termed mitotic slippage that involves the degradation of cyclin B1 without mitotic checkpoint inactivation. Inducing mitotic slippage with chemicals causes cells to die after multiple rounds of DNA replication without cell division, which may enhance the antitumor activity of microtubule-targeting drugs. Here, we explore pathways leading to mitotic slippage by using SU6656 and geraldol, two recently identified chemical inducers of mitotic slippage. Mitotic slippage induced by SU6656 or geraldol was blocked by the proteasome inhibitor MG-132 and involved proteasome-dependent degradation of cyclin B1 and the mitotic checkpoint proteins budding uninhibited by benzimidazole related 1 (BubR1) and cell division cycle 20 (Cdc20) in T98G cells. Mitotic slippage and the degradation of BubR1 and Cdc20 were also inhibited by the caspase-3 and -7 inhibitor DEVD-CHO. MCF-7 cells lacking caspase-3 expression could not degrade BubR1 or undergo mitotic slippage in response to SU6656 or geraldol. Introduction of caspase-3 completely restored the ability of MCF-7 cells to degrade BubR1 and undergo mitotic slippage. However, lack of expression of caspase-3 did not affect cell death after exposure to paclitaxel, with or without mitotic slippage induction. The requirement for caspase-3 for chemically induced mitotic slippage reveals a new mechanism for mitotic exit and a link between mitosis and apoptosis that has implications for the outcome of cancer chemotherapy. PMID:21441410

Riffell, Jenna L; Jänicke, Reiner U; Roberge, Michel



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

PubMed Central

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

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




Microsoft Academic Search

An auditory feature extraction algorithm for robust speech recognition in adverse acoustic environments is proposed. Based on the analysis of human auditory system, the fea- ture extraction algorithm consists of several modules: FFT, outer-middle-ear transfer function, frequency conversion from linear to Bark scales, auditory filtering,nonlinearity, and dis- crete cosine transform. Three recognition experiments have been conducted on connected digit recognition

Qi Li; Frank K. Soong; Olivier Siohan



Localization of topoisomerase II in mitotic chromosomes  

PubMed Central

In the preceding article we described a polyclonal antibody that recognizes cSc-1, a major polypeptide component of the chicken mitotic chromosome scaffold. This polypeptide was shown to be chicken topoisomerase II. In the experiments described in the present article we use indirect immunofluorescence and immunoelectron microscopy to examine the distribution of topoisomerase II within intact chromosomes. We also describe a simple experimental protocol that differentiates antigens that are interspersed along the chromatin fiber from those that occupy restricted domains within the chromosome. These experiments indicate that the distribution of the enzyme appears to be independent of the bulk chromatin. Our data suggest that topoisomerase II is bound to the bases of the radial loop domains of mitotic chromosomes. PMID:2985626



A Neural Adaptive Algorithm for Feature Selection and Classification of High Dimensionality Data  

Microsoft Academic Search

In this paper, we propose a novel method which involves neural adaptive techniques for identifying salient features and for classifying high di- mensionality data. In particular a network pruning algorithm acting on Multi- Layer Perceptron topology is the foundation of the feature selection strategy. Feature selection is implemented within the back-propagation learning process and based on a measure of saliency

Elisabetta Binaghi; Ignazio Gallo; Mirco Boschetti; Pietro Alessandro Brivio



A human homolog of Drosophila warts tumor suppressor, h-warts, localized to mitotic apparatus and specifically phosphorylated during mitosis  

Microsoft Academic Search

We identified a human homolog of Drosophila warts tumor suppressor gene, termed h-warts, which was mapped at chromosome 6q24-25.1. The h-warts protein has a serine\\/threonine kinase domain and is localized to centrosomes in interphase cells. However, it becomes localized to the mitotic apparatus, including spindle pole bodies, mitotic spindle, and midbody, in a highly dynamic manner during mitosis. Furthermore, h-warts

Yasuyuki Nishiyama; Toru Hirota; Tetsuro Morisaki; Toshihiro Hara; Tomotoshi Marumoto; Shin-ichi Iida; Keishi Makino; Hideyuki Yamamoto; Takehisa Hiraoka; Nobuo Kitamura; Hideyuki Saya



Nuclear Chk1 prevents premature mitotic entry.  


Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry. PMID:21628425

Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki



Microtubule-dependent regulation of mitotic protein degradation  

PubMed Central

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

Song, Ling; Craney, Allison; Rape, Michael



Differential Mitotic Stability of Yeast Disomes Derived from Triploid Meiosis  

PubMed Central

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

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



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

NASA Astrophysics Data System (ADS)

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

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



Fusing High and Low-Level Features for Handwritten Word Recognition  

Microsoft Academic Search

This paper presents a novel approach that combines high level and low level features for the recognition of handwritten words. Given a word image, high level fea- tures are extracted from loosely segmented words. Such features are used with an HMM word classifier in a lexicon-driven approach. This classifier produces at the output a ranked list of the N-best recognition

Alessandro L. Koerich; Alceu S. Britto Jr; Robert Sabourin


Object Recognition in High Clutter Images Using Line Features Philip David  

E-print Network

Object Recognition in High Clutter Images Using Line Features Philip David ¢¡ £ and Daniel De that uses model and image line features to locate complex objects in high clutter environments. Finding and range search algorithms are used to implement a distance measure that is unaffected by clutter

DeMenthon, Daniel


Mitotic arrest and slippage induced by pharmacological inhibition of Polo-like kinase 1.  


Exposure to drugs that interfere with microtubule dynamics block cell cycle progression at mitosis by prolonged activation of the spindle assembly checkpoint (SAC). Cells can evade mitotic arrest and proceed to interphase without chromosome segregation by a process termed mitotic slippage that involves Cyclin B1 degradation without checkpoint inactivation. Here, we explored the cellular response to small-molecule inhibitors of Polo-like kinase 1 (Plk1), an important regulator of cell division. We found that the clinical Plk1 inhibitors BI 2536 and BI 6727, both unexpectedly, induced a dose-dependent cellular drug response: While mitotic arrest was induced in cancer cell lines and primary non-transformed cells across the entire range of concentrations tested, only high concentrations seemed to promote mitotic slippage. Since this observation contrasts with the effects expected from studies reporting RNAi-mediated Plk1 depletion in cancer cells, we wondered whether both ATP-competitive inhibitors target unknown kinases that are involved in signaling from the spindle assembly checkpoint (SAC) and might contribute to the mitotic slippage. A chemical proteomics approach used to profile the selectivity of both inhibitors revealed that SAC kinases are not targeted directly. Still, the activities of Cdk1/Cyclin B1 and Aurora B, which plays important roles in the error correction of false microtubule-kinetochore attachments and in checkpoint signaling, were shown to be downregulated at high inhibitor concentrations. Our data suggest that the inhibition of Plk1 activity below a certain threshold influences Aurora B activity via reduced phosphorylation of Fox M1 and Survivin leading to diminished levels of Aurora B protein and alteration of its subcellular localization. Within the spectrum of SAC proteins that are degraded during mitotic slippage, the degradation of Cyclin B1 and the downregulation of Aurora B activity by Plk1 inhibition seem to be critical promoters of mitotic slippage. The results indicate that careful dose-finding studies in cancer trials are necessary to limit or even prevent mitotic slippage, which could be associated with improved cancer cell survival. PMID:25169932

Raab, Monika; Krämer, Andrea; Hehlgans, Stephanie; Sanhaji, Mourad; Kurunci-Csacsko, Elisabeth; Dötsch, Christina; Bug, Gesine; Ottmann, Oliver; Becker, Sven; Pachl, Fiona; Kuster, Bernhard; Strebhardt, Klaus



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



Pulmonary Gaucher's disease: High-resolution computed tomographic features  

Microsoft Academic Search

CT findings in pulmonary Gaucher's disease have not been previously reported. Chest radiograph of a patient with pulmonary involvement in type I Gaucher's disease proven by biopsy showed linear and reticulo-nodular opacities. High-resolution CT demonstrated thickening of the interlobular septa and between four and six small nodules within secondary lobules, probably each corresponding to an acinus.

A. Tunaci; Y. M. Berkmen; E. Gökmen



Feature processing during high-rate auditory selective attention  

Microsoft Academic Search

Auditory event-related brain potentials (ERPs) and reaction times were, analyzed in a selective attention task in which subjects\\u000a attended to tone pips presented at high rates-Xinterstimulua intervals [ISIs] of 40-200 msec). Subjects responded to infrequent\\u000a target tones of a specified frequency (250 or 4000 Hz) and location (left or right ear) that were louder than otherwise identical\\u000a tones presented randomly

David L. Woods; Claude Alain



Optimal Feature Selection in High-Dimensional Discriminant Analysis  

PubMed Central

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

Kolar, Mladen; Liu, Han



A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit  

PubMed Central

Summary Mixed Lineage Leukemia (MLL) and its metazoan orthologs have been linked with the epigenetic maintenance of transcriptional activity. To identify mechanisms by which MLL might perpetuate active transcription in dividing cells, we investigated its role during M-phase of the cell cycle. Unlike other histone methyltransferases examined, MLL remained globally embedded within condensed mitotic chromosomes. Genome-wide location analysis revealed a rearranged pattern of MLL occupancy in mitosis compared with interphase, characterized by a strong preference for MLL to occupy genes in mitosis possessing the highest levels of interphase transcription. Knockdown experiments revealed that MLL is required for rapid post-mitotic reactivation of its mitotic target genes, suggesting a bookmarking function. MLL tethers Menin, RbBP5, and ASH2L to genes during mitosis, but is dispensable for preserving H3K4 methylation. These findings implicate mitotic retention as a novel component of MLL-based gene regulation which may facilitate inheritance of active gene expression states during cell division. PMID:20064463

Blobel, Gerd A.; Kadauke, Stephan; Wang, Eric; Lau, Alan W.; Zuber, Johannes; Chou, Margaret M.; Vakoc, Christopher R.



Micalastic high-voltage insulation: Design features and experience  

NASA Astrophysics Data System (ADS)

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

Wichmann, A.



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: 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



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



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


Nanostructure based color filtering has been considered an attractive replacement for current colorant pigmentation in the display technologies, in view of its increased efficiencies, ease of fabrication and eco-friendliness. For such structural filtering, iridescence relevant to its angular dependency, which poses a detrimental barrier to the practical development of high performance display and sensing devices, should be mitigated. We report on a non-iridescent transmissive structural color filter, fabricated in a large area of 76.2 × 25.4?mm(2), taking advantage of a stack of three etalon resonators in dielectric films based on a high-index cavity in amorphous silicon. The proposed filter features a high transmission above 80%, a high excitation purity of 0.93 and non-iridescence over a range of 160°, exhibiting no significant change in the center wavelength, dominant wavelength and excitation purity, which implies no change in hue and saturation of the output color. The proposed structure may find its potential applications to large-scale display and imaging sensor systems. PMID:24815530

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



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

NASA Astrophysics Data System (ADS)

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.

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



Induction of mitotic aneuploidy in lower eukaryotes  

SciTech Connect

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

Kappas, A. [National Research Center Democritus, Athens (Greece)



Hydroxyl free radicals generated by vanadyl[IV] induce cell blebbing in mitotic human Chang liver cells.  


Vanadium has recently been reported to induce interphase and M-phase (mitotic) programmed cell death via the generation of hydroxyl free radicals (OH*). In this paper, the effects of antioxidants on: (a) vanadyl[IV]-generated OH* free radical levels; and (b) cellular glutathione in vanadyl [IV]-treated Chang liver cells were evaluated. The surface morphology of vanadyl-treated mitotic cells was studied by confocal and scanning microscopy. The free radical scavengers zinc chloride, glucose and thiourea reduced the levels of vanadyl-induced OH* free radicals and partially prevented the depletion of cellular glutathione. Concurrent with OH* free radical production, vanadyl-treated telophase cells exhibited excessive cell blebbing and cell shrinkage. The morphological features demonstrated in vanadyl-induced mitotic programmed cell death as a consequence of oxidative stress is novel. PMID:9210293

Bay, B H; Sit, K H; Paramanantham, R; Chan, Y G



Amyloid Features and Neuronal Toxicity of Mature Prion Fibrils Are Highly Sensitive to High Pressure*  

PubMed Central

Prion proteins (PrP) can aggregate into toxic and possibly infectious amyloid fibrils. This particular macrostructure confers on them an extreme and still unexplained stability. To provide mechanistic insights into this self-assembly process, we used high pressure as a thermodynamic tool for perturbing the structure of mature amyloid fibrils that were prepared from recombinant full-length mouse PrP. Application of high pressure led to irreversible loss of several specific amyloid features, such as thioflavin T and 8-anilino-1-naphthalene sulfonate binding, alteration of the characteristic proteinase K digestion pattern, and a significant decrease in the ?-sheet structure and cytotoxicity of amyloid fibrils. Partial disaggregation of the mature fibrils into monomeric soluble PrP was observed. The remaining amyloid fibrils underwent a change in secondary structure that led to morphologically different fibrils composed of a reduced number of proto-filaments. The kinetics of these reactions was studied by recording the pressure-induced dissociation of thioflavin T from the amyloid fibrils. Analysis of the pressure and temperature dependence of the relaxation rates revealed partly unstructured and hydrated kinetic transition states and highlighted the importance of collapsing and hydrating inter- and intramolecular cavities to overcome the high free energy barrier that stabilizes amyloid fibrils. PMID:21357423

El Moustaine, Driss; Perrier, Veronique; Van Ba, Isabelle Acquatella-Tran; Meersman, Filip; Ostapchenko, Valeriy G.; Baskakov, Ilia V.; Lange, Reinhard; Torrent, Joan



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)



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


The spindle assembly checkpoint (SAC) is a conserved mechanism that ensures the fidelity of chromosome distribution in mitosis by preventing anaphase onset until the correct bipolar microtubule-kinetochore attachments are formed. Errors in SAC function may contribute to tumorigenesis by inducing numerical chromosome anomalies (aneuploidy). On the other hand, total disruption of SAC can lead to massive genomic imbalance followed by cell death, a phenomena that has therapeutic potency. We performed a cell-based high-throughput screen with a compound library of 2000 bioactives for novel SAC inhibitors and discovered a plant-derived phenolic compound eupatorin (3',5-dihydroxy-4',6,7-trimethoxyflavone) as an anti-mitotic flavonoid. The premature override of the microtubule drug-imposed mitotic arrest by eupatorin is dependent on microtubule-kinetochore attachments but not interkinetochore tension. Aurora B kinase activity, which is essential for maintenance of normal SAC signaling, is diminished by eupatorin in cells and in vitro providing a mechanistic explanation for the observed forced mitotic exit. Eupatorin likely has additional targets since eupatorin treatment of pre-mitotic cells causes spindle anomalies triggering a transient M phase delay followed by impaired cytokinesis and polyploidy. Finally, eupatorin potently induces apoptosis in multiple cancer cell lines and suppresses cancer cell proliferation in organotypic 3D cell culture model. PMID:22227008

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



Identification of a mitotic death signature in cancer cell lines.  


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

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



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)



Centromere fragmentation is a common mitotic defect of S and G2 checkpoint override  

PubMed Central

DNA damaging agents, including those used in the clinic, activate cell cycle checkpoints, which blocks entry into mitosis. Given that checkpoint override results in cell death via mitotic catastrophe, inhibitors of the DNA damage checkpoint are actively being pursued as chemosensitization agents. Here we explored the effects of gemcitabine in combination with Chk1 inhibitors in a panel of pancreatic cancer cell lines and found variable abilities to override the S phase checkpoint. In cells that were able to enter mitosis, the chromatin was extensively fragmented, as assessed by metaphase spreads and Comet assay. Notably, electron microscopy and high-resolution light microscopy showed that the kinetochores and centromeres appeared to be detached from the chromatin mass, in a manner reminiscent of mitosis with unreplicated genomes (MUGs). Cell lines that were unable to override the S phase checkpoint were able to override a G2 arrest induced by the alkylator MMS or the topoisomerase II inhibitors doxorubicin or etoposide. Interestingly, checkpoint override from the topoisomerase II inhibitors generated fragmented kinetochores (MUGs) due to unreplicated centromeres. Our studies show that kinetochore and centromere fragmentation is a defining feature of checkpoint override and suggests that loss of cell viability is due in part to acentric genomes. Furthermore, given the greater efficacy of forcing cells into premature mitosis from topoisomerase II-mediated arrest as compared with gemcitabine-mediated arrest, topoisomerase II inhibitors maybe more suitable when used in combination with checkpoint inhibitors. PMID:23624842

Beeharry, Neil; Rattner, Jerome B.; Caviston, Juliane P.; Yen, Tim



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

NASA Technical Reports Server (NTRS)

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

Blaney, D. L.; Crisp, D.



A monoclonal antibody to a mitotic microtubule-associated protein blocks mitotic progression  

PubMed Central

A monoclonal antibody raised against mitotic spindles isolated from CHO cells ([CHO1], Sellitto, C., and R. Kuriyama. 1988. J. Cell Biol. 106:431-439) identifies an epitope that resides on polypeptides of 95 and 105 kD and is localized in the spindles of diverse organisms. The antigen is distributed throughout the spindle at metaphase but becomes concentrated in a progressively narrower zone on either side of the spindle midplane as anaphase progresses. Microinjection of CHO1, either as an ascites fluid or as purified IgM, results in mitotic inhibition in a stage-specific and dose-dependent manner. Parallel control injections with nonimmune IgMs do not yield significant mitotic inhibition. Immunofluorescence analysis of injected cells reveals that those which complete mitosis display normal localization of CHO1, whereas arrested cells show no specific localization of the CHO1 antigen within the spindle. Immunoelectron microscopic images of such arrested cells indicate aberrant microtubule organization. The CHO1 antigen in HeLa cell extracts copurifies with taxol-stabilized microtubules. Neither of the polypeptides bearing the antigen is extracted from microtubules by ATP or GTP, but both are approximately 60% extracted with 0.5 M NaCl. Sucrose gradient analysis reveals that the antigens sediment at approximately 11S. The CHO 1 antigen appears to be a novel mitotic MAP whose proper distribution within the spindle is required for mitosis. The properties of the antigen(s) suggest that the corresponding protein(s) are part of the mechanism that holds the antiparallel microtubules of the two interdigitating half spindles together during anaphase. PMID:2199459



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

SciTech Connect

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

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



Budding Yeast Swe1 Is Involved in the Control of Mitotic Spindle Elongation and Is Regulated by Cdc14 Phosphatase during Mitosis.  


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

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



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

PubMed Central

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

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



An unsupervised feature extraction method for high dimensional image data compaction  

NASA Technical Reports Server (NTRS)

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

Ghassemian, Hassan; Landgrebe, David



An Evaluation of Feature Learning Methods for High Resolution Image Classification  

NASA Astrophysics Data System (ADS)

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

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



Feature selection, mutual information, and the classification of high-dimensional patterns  

Microsoft Academic Search

We propose a novel feature selection filter for supervised learning, which relies on the efficient estimation of the mutual\\u000a information between a high-dimensional set of features and the classes. We bypass the estimation of the probability density\\u000a function with the aid of the entropic-graphs approximation of Rényi entropy, and the subsequent approximation of the Shannon\\u000a entropy. Thus, the complexity does

Boyan Bonev; Francisco Escolano; Miguel Cazorla



The Nek6 and Nek7 Protein Kinases Are Required for Robust Mitotic Spindle Formation and Cytokinesis ? §  

PubMed Central

Nek6 and Nek7 are members of the NIMA-related serine/threonine kinase family. Previous work showed that they contribute to mitotic progression downstream of another NIMA-related kinase, Nek9, although the roles of these different kinases remain to be defined. Here, we carried out a comprehensive analysis of the regulation and function of Nek6 and Nek7 in human cells. By generating specific antibodies, we show that both Nek6 and Nek7 are activated in mitosis and that interfering with their activity by either depletion or expression of reduced-activity mutants leads to mitotic arrest and apoptosis. Interestingly, while completely inactive mutants and small interfering RNA-mediated depletion delay cells at metaphase with fragile mitotic spindles, hypomorphic mutants or RNA interference treatment combined with a spindle assembly checkpoint inhibitor delays cells at cytokinesis. Importantly, depletion of either Nek6 or Nek7 leads to defective mitotic progression, indicating that although highly similar, they are not redundant. Indeed, while both kinases localize to spindle poles, only Nek6 obviously localizes to spindle microtubules in metaphase and anaphase and to the midbody during cytokinesis. Together, these data lead us to propose that Nek6 and Nek7 play independent roles not only in robust mitotic spindle formation but also potentially in cytokinesis. PMID:19414596

O'Regan, Laura; Fry, Andrew M.



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

PubMed Central

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

Zong, Lin; Lin, Ming; Fan, Xinmin



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



Control of the mitotic exit network during meiosis  

E-print Network

The mitotic exit network (MEN) is an essential GTPase signaling pathway that triggers exit from mitosis in budding yeast. We show here that during meiosis, the MEN is dispensable for exit from meiosis I but contributes to ...

Attner, Michelle Andrea


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



Mitotic Variations in the Lens Epithelium of the Frog  

Microsoft Academic Search

(1) This account presents the results of a series of studies on variations in the mitotic index of frog lens epithelium.(2) Seasonal variations in mitotic index have been found in the lenses of R.catesbeiana and R.pipiens. Though the numbers of division figures vary considerably, it can be concluded that in the winter months cellular reproduction is a comparatively rare event

D. M. Rosenbaum; H. Rothstein



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



Micromechanical-biochemical studies of mitotic chromosome elasticity and structure  

NASA Astrophysics Data System (ADS)

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

Poirier, Michael Guy


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.



Imaging protein dynamics in live mitotic cells  

PubMed Central

To ensure that genetic material is accurately segregated during mitosis, eukaryotic cells assemble a mitotic spindle, a dynamic structure composed of microtubules and associated regulatory, structural and motor proteins. Although much has been learned in the past decades from direct observations of live cells expressing fluorescently tagged spindle proteins, a complete understanding of spindle assembly requires a detailed analysis of the dynamic behavior of component parts. Proteins tagged with conventional fluorophores, however, make such an analysis difficult because all of the molecules are uniformly fluorescent. To alleviate this problem, we have tagged proteins with a photoactivatable variant of GFP (PA-GFP), thereby allowing one to follow the behavior of a subset of tagged molecules in the cell. Here, we describe methods to tag and express proteins with PA-GFP, locally photoactivate the recombinant protein and record the dynamic behavior of the photoactivated molecules in live cells. We provide examples of photoactivable proteins in mammalian and yeast cells to illustrate the power of this approach to examine the dynamics of spindle formation and function in diverse cells. PMID:20085816

Ferenz, Nick P.; Ma, Nan; Lee, Wei-Lih; Wadsworth, Patricia



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; Strömberg, Thomas; Axelson, Magnus; Abrahmsén, Lars; Lindqvist, Arne; Larsson, Olle; Aleem, Eiman



Feature selection for high dimensional regression using local search and statistical criteria  

E-print Network 1 Motivation Genomic selection is a genetic evaluation of animals from their DNA (extracted usingFeature selection for high dimensional regression using local search and statistical criteria J, an important objective of genomic selection consists in searching explicative markers for a phenotype

Boyer, Edmond


Speaker Verification via High-Level Feature Based Phonetic-Class Pronunciation Modeling  

E-print Network

1 Speaker Verification via High-Level Feature Based Phonetic-Class Pronunciation Modeling Shi proposes to mitigate this problem by grouping similar phonemes into phonetic classes and representing background and speaker models as phonetic-class dependent density functions. Phonemes are grouped by (1

Mak, Man-Wai


ESC observations of SN 2005cf. II. Optical spectroscopy and the high-velocity features  

NASA Astrophysics Data System (ADS)

The ESC-RTN optical spectroscopy data set for SN 2005cf is presented and analyzed. The observations range from -11.6 and +77.3 days with respect to B-band maximum light. The evolution of the spectral energy distribution of SN 2005cf is characterized by the presence of high velocity Si II and Ca II features. SYNOW synthetic spectra are used to investigate the ejecta geometry of silicon. Based on the synthetic spectra, the Si II high-velocity feature appears detached at 19 500 km s-1. We also securely establish the presence of such a feature in SN 1990N, SN 1994D, SN 2002er, and SN 2003du. In a morphological study both the Ca II IR triplet and H&K absorption lines of SN 2005cf show high-velocity features centered around 24 000 km s-1. When compared with other type Ia SNe based on the scheme presented in [CITE][ApJ, 623, 1011]2005ApJ...623.1011B, SN 2005cf definitely belongs to the LVG group. All individual spectra are only available in electronic form at the CDS via anonymous ftp to ( or via Tables [see full text]- [see full text] are only available in electronic form at

Garavini, G.; Nobili, S.; Taubenberger, S.; Pastorello, A.; Elias-Rosa, N.; Stanishev, V.; Blanc, G.; Benetti, S.; Goobar, A.; Mazzali, P. A.; Sanchez, S. F.; Salvo, M.; Schmidt, B. P.; Hillebrandt, W.



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


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



High velocity features in Type Ia supernovae via interaction with circumstellar shell  

NASA Astrophysics Data System (ADS)

Observations of Type Ia supernovae (SN Ia) in the weeks before B-band maximum (Bmax) have shown the presence of Ca, Si, and Fe features with velocities of 8,000-14,000 km/s faster than that associated with the photospheric features (PSF). Suggestions for the source of the high velocity features include interaction of the ejecta with a circumstellar material. We perform hydrodynamic simulation of a supernova interacting with a shell consisting of 5×10-3 M? of material and an outer radius of 0.028 R? as well as a supernova in a low density circumstellar medium (LDCSM) without a shell. We present the synthetic spectra of the Ca II near-IR feature generated from both models fit to the observed features in SN 2011fe in the epoch before Bmax. The shell interaction model consistently fits the observed spectra better than the LDCSM model at all times before Bmax, and satisfies the observed velocity evolution of both the HVF and PSF.

Mulligan, Brian W.; Wheeler, J. Craig



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


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



APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and cytoskeletal regulation  

PubMed Central

To ensure the accurate transmission of genetic material, chromosome segregation must occur with extremely high fidelity. Segregation errors lead to chromosomal instability (CIN), with deleterious consequences. Mutations in the tumor suppressor adenomatous polyposis coli (APC) initiate most colon cancers and have also been suggested to promote disease progression through increased CIN, but the mechanistic role of APC in preventing CIN remains controversial. Using fly embryos as a model, we investigated the role of APC proteins in CIN. Our findings suggest that APC2 loss leads to increased rates of chromosome segregation error. This occurs through a cascade of events beginning with incomplete centrosome separation leading to failure to inhibit formation of ectopic cleavage furrows, which result in mitotic defects and DNA damage. We test several hypotheses related to the mechanism of action of APC2, revealing that APC2 functions at the embryonic cortex with several protein partners, including Axin, to promote mitotic fidelity. Our in vivo data demonstrate that APC2 protects genome stability by modulating mitotic fidelity through regulation of the cytoskeleton. PMID:24026117

Poulton, John S.; Mu, Frank W.; Roberts, David M.; Peifer, Mark



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.



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

NASA Astrophysics Data System (ADS)

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

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



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



Mitotic Chromosome Loss in a Disomic Haploid of SACCHAROMYCES CEREVISIAE  

PubMed Central

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

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



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.



The Effect of High vs Low Density Barium Preparations on the Quantitative Features of Swallowing  

Microsoft Academic Search

We compared the effect of high-density and low-density barium preparations on the quantitative features of swallowing. The two barium preparations differed primarily in density but also differed somewhat in viscosity. Concurrent videofluoroscopic and manometric studies were done in nine healthy control subjects. Videofluoroscopy was recorded in the lateral projection at 30 frames\\/sec while concurrent manometry was done with five intraluminal

Wylie J. Dodds; Benson T. Massey; Mark K. Kern



High-resolution rocket spectra of the 1920-A and 1720-A features in the spectrum of Zeta Tauri  

NASA Technical Reports Server (NTRS)

High-resolution ultraviolet spectrograms of the B-shell star Zeta Tau reveal two features characteristic of B supergiants, one at 1720 A and the other at 1920 A. The presence of these features in the spectrum of this object shows that they are indicative of an extended atmosphere - either the tenuous atmosphere of a supergiant or the envelope surrounding a rapidly rotating main-sequence star - and are therefore not purely luminosity criteria. The high spectral resolution allows an identification of the contributors to these features. The dominant contributor to the 1920-A feature is Fe III, while the primary contributor to the 1720-A feature is Al II.

Heap, S. R.



Detection of sub-kilometer craters in high resolution planetary images using shape and texture features  

NASA Astrophysics Data System (ADS)

Counting craters is a paramount tool of planetary analysis because it provides relative dating of planetary surfaces. Dating surfaces with high spatial resolution requires counting a very large number of small, sub-kilometer size craters. Exhaustive manual surveys of such craters over extensive regions are impractical, sparking interest in designing crater detection algorithms (CDAs). As a part of our effort to design a CDA, which is robust and practical for planetary research analysis, we propose a crater detection approach that utilizes both shape and texture features to identify efficiently sub-kilometer craters in high resolution panchromatic images. First, a mathematical morphology-based shape analysis is used to identify regions in an image that may contain craters; only those regions - crater candidates - are the subject of further processing. Second, image texture features in combination with the boosting ensemble supervised learning algorithm are used to accurately classify previously identified candidates into craters and non-craters. The design of the proposed CDA is described and its performance is evaluated using a high resolution image of Mars for which sub-kilometer craters have been manually identified. The overall detection rate of the proposed CDA is 81%, the branching factor is 0.14, and the overall quality factor is 72%. This performance is a significant improvement over the previous CDA based exclusively on the shape features. The combination of performance level and computational efficiency offered by this CDA makes it attractive for practical application.

Bandeira, Lourenço; Ding, Wei; Stepinski, Tomasz F.



High performance 32nm logic technology featuring 2nd generation high-k + metal gate transistors  

Microsoft Academic Search

A 32 nm logic technology for high performance microprocessors is described. 2nd generation high-k + metal gate transistors provide record drive currents at the tightest gate pitch reported for any 32 nm or 28 nm logic technology. NMOS drive currents are 1.62 mA\\/um Idsat and 0.231 mA\\/um Idlin at 1.0 V and 100 nA\\/um Ioff. PMOS drive currents are 1.37

P. Packan; S. Akbar; M. Armstrong; D. Bergstrom; M. Brazier; H. Deshpande; K. Dev; G. Ding; T. Ghani; O. Golonzka; W. Han; J. He; R. Heussner; R. James; J. Jopling; C. Kenyon; S.-H. Lee; M. Liu; S. Lodha; B. Mattis; A. Murthy; L. Neiberg; J. Neirynck; S. Pae; C. Parker; L. Pipes; J. Sebastian; J. Seiple; B. Sell; A. Sharma; S. Sivakumar; B. Song; A. St. Amour; K. Tone; T. Troeger; C. Weber; K. Zhang; Y. Luo; S. Natarajan



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



Topoisomerase II is a structural component of mitotic chromosome scaffolds  

PubMed Central

We have obtained a polyclonal antibody that recognizes a major polypeptide component of chicken mitotic chromosome scaffolds. This polypeptide migrates in SDS PAGE with Mr 170,000. Indirect immunofluorescence and subcellular fractionation experiments confirm that it is present in both mitotic chromosomes and interphase nuclei. Two lines of evidence suggest that this protein is DNA topoisomerase II, an abundant nuclear enzyme that controls DNA topological states: anti-scaffold antibody inhibits the strand-passing activity of DNA topoisomerase II; and both anti-scaffold antibody and an independent antibody raised against purified bovine topoisomerase II recognize identical partial proteolysis fragments of the 170,000-mol-wt scaffold protein in immunoblots. Our results suggest that topoisomerase II may be an enzyme that is also a structural protein of interphase nuclei and mitotic chromosomes. PMID:2985625



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


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



Mitotic Count by Phosphohistone H3 Immunohistochemical Staining Predicts Survival and Improves Interobserver Reproducibility in Well-differentiated Neuroendocrine Tumors of the Pancreas.  


Well-differentiated neuroendocrine tumors (WDNETs) of the pancreas are graded on the basis of mitotic count or Ki67 index. Mitotic count has a narrow cutoff; its assessment is time consuming and carries poor interobserver reproducibility. Phosphohistone H3 (PHH3) is a mitosis-specific marker whose value has been validated in several tumor types. We sought to assess the utility of PHH3 in histologic grading of pancreatic WDNETs. Sixty-three cases of surgically resected primary pancreatic WDNETs were retrieved, and immunohistochemical analysis for PHH3 and Ki67 was performed. Mitotic rate was independently assessed by 4 pathologists on hematoxylin and eosin (HE; in 50 high-power fields [HPFs], expressed as mitoses/10 HPF) and PHH3 stains (in 50 HPFs, one 10×, and one 20× hotspot). PHH3 and Ki67 labeling indices were determined on a single 20× hotspot and expressed as the percentage of positive cells to total cells. We found that mitotic counts by various methods significantly correlated with each other and also with PHH3 and Ki67 indices, with the best correlation seen within the 3 different PHH3 counts (in 50 HPFs, one 10× and one 20× hotspot). Moreover, mitotic count on PHH3 was less time consuming than that on HE (1.68 vs. 3.67 min for 50 HPFs, P<0.0001). Histologic grade determined by PHH3 significantly correlated with disease-specific and disease-free survivals, with the best cutoffs of ?4 mitoses/10 HPF (2 mm), ?7 mitoses/10× hotspot, ?5 mitoses/20× hotspot (log rank test, P<0.0001), and ?0.16% for PHH3 labeling index (log rank test, P<0.0006). Tumor grades based on PHH3 stain also showed significant correlation with patient survivals in multivariate Cox proportional hazards models (P<0.05). Histologic grades by mitotic counts on PHH3 demonstrated high concordance and ? agreement with grades determined by mitotic count on HE. PHH3 stain also showed improved interobserver agreement in both original mitotic count (intraclass correlation 0.98 vs. 0.79) and final grade assignment (Fleiss ? 0.69 vs. 0.46) as compared with HE. Thus, our data confirmed that histologic grading by PHH3 stain has practical and prognostic values and offers reduced time and improved interobserver reproducibility in mitotic rate assessment and grade assignment. Although larger series are needed for validation, mitotic rate can potentially be determined by counting 1 hotspot, which will greatly facilitate the assessment of histologic grade in pancreatic WDNETs. PMID:25353284

Voss, Sarah M; Riley, Meghan P; Lokhandwala, Parvez M; Wang, Ming; Yang, Zhaohai



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 Flade Ice Blink as taken by Michael Studdinger/NASA

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



Yeast haspin kinase regulates polarity cues necessary for mitotic spindle positioning and is required to tolerate mitotic arrest.  


Haspin is an atypical protein kinase that in several organisms phosphorylates histone H3Thr3 and is involved in chromosome segregation. In Saccharomyces cerevisiae, H3Thr3 phosphorylation has never been observed and the function of haspin is unknown. We show that deletion of ALK1 and ALK2 haspin paralogs causes the mislocalization of polarisome components. Following a transient mitotic arrest, this leads to an overly polarized actin distribution in the bud where the mitotic spindle is pulled. Here it elongates, generating anucleated mothers and binucleated daughters. Reducing the intensity of the bud-directed pulling forces partially restores proper cell division. We propose that haspin controls the localization of polarity cues to preserve the coordination between polarization and the cell cycle and to tolerate transient mitotic arrests. The evolutionary conservation of haspin and of the polarization mechanisms suggests that this function of haspin is likely shared with other eukaryotes, in which haspin may regulate asymmetric cell division. PMID:23973165

Panigada, Davide; Grianti, Paolo; Nespoli, Alessandro; Rotondo, Giuseppe; Castro, Daniela Gallo; Quadri, Roberto; Piatti, Simonetta; Plevani, Paolo; Muzi-Falconi, Marco



Spectral feature design for data compression in high dimensional multispectral data  

NASA Technical Reports Server (NTRS)

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

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



High-resolution spectra of the 3.29 micron interstellar emission feature - A summary  

NASA Technical Reports Server (NTRS)

High spectral resolution observations of the 3.29-micron interstellar emission feature show two types of profiles. Type 1 has a central wavelength of 3.289-micron and is observed in extended objects such as planetary nebulae and H II regions. Type 2 has a central wavelength of 3.296 microns and is observed around a small number of stellar sources. Type 2 has a full width at half-maximum of 0.020 micron; Type 1 has a broader FWHM, perhaps as much as 0.042 micron, but this is uncertain because of contamination by Pf(delta) emission. These profiles are tabulated for comparison to laboratory data. It is found that no proposed identification for the 3.29-micron emission feature definitely matches the observational spectra, although amorphous aromatic materials and heated polycyclic aromatic hydrocarbons tend to fit the best.

Tokunaga, A. T.; Sellgren, K.; Smith, R. G.; Nagata, T.; Sakata, A.; Nakada, Y.



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

PubMed Central

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

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



High-resolution spectroscopy of the 3 micron emission features in NGC 7027 and IRAS 21282+5050  

NASA Technical Reports Server (NTRS)

High-resolution 3 micron spectra of NGC 7027 and IRAS 21282+5050 are presented. The well-known 3.29 micron emission feature has very similar shapes in the two objects, but a small shift is present between them. The emission features at 3.46 and 3.52 microns recently found in IRAS 21282+5050 are also present in the spectrum of NGC 7027. In addition, there may be two other weak features at 3.55 and 3.58 microns in NGC 7027. These emission features might be related to saturated hydrocarbons. The spectra provide further constraints on the origin of the 'unidentified' emission features.

Nagata, Tetsuya; Tokunaga, Alan T.; Sellgren, K.; Smith, Robert G.; Onaka, Takashi



Mitotic Spindle Proteomics in Chinese Hamster Ovary Mary Kate Bonner1  

E-print Network

Mitotic Spindle Proteomics in Chinese Hamster Ovary Cells Mary Kate Bonner1 , Daniel S. Poole1 events. Here, we report a proteomic study of the mitotic spindle from Chinese Hamster Ovary (CHO) cells A, Yates JR III, et al. (2011) Mitotic Spindle Proteomics in Chinese Hamster Ovary Cells. PLoS ONE 6

Skop, Ahna


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; Gorjánácz, Mátyás; Davidson, Iain F.; Nga Ly-Hartig, Thi Bach; Ellenberg, Jan



Periodic mitotic events induced in the absence of DNA replication.  


We have discovered and report here a means of separating a mitotic "subcycle" from the G1- and S-phase events of the mammalian cell cycle. Time-lapse videomicroscopy of Syrian hamster fibroblast (BHK) cells revealed that caffeine could induce multiple entries into mitosis while cells were blocked in DNA synthesis. As with normal mitoses, the abundance of mitosis-specific phosphoproteins was coupled with the condensation of chromatin. The BHK temperature-sensitive mutant tsBN2 also completed multiple entries into mitosis while arrested during DNA replication and raised to the restrictive temperature. Periodic mitotic events occurred even when BHK cells were exposed to low concentrations of serum or cycloheximide, conditions that prevent the cycling of BHK cells by blocking their entry into S phase. These results suggest that an oscillation governing the activation and inactivation of mitotic factors can be generated in mammalian cells and uncoupled from the G1 and DNA replication events of the normal cell cycle. This system will be useful for examining the molecular nature of mitotic factors. PMID:3480528

Schlegel, R; Pardee, A B



424 Preliminary notes v-Bodies in mitotic chromatin  

E-print Network

, The University of Tennessee, Oak Ridge Graduate School of Biomedical Sciences, and Biology Division, Oak Ridge National Laboratory,' Oak Ridge, TN 37830, USA Summary. Electron micrographs of mitotic chromo- somal line CHO-K,, a clone of CHO cells, was used in this study; its physiological and biochemical properties

Olins, Ada L.


Mitotic death: a mechanism of survival? A review  

Microsoft Academic Search

Mitotic death is a delayed response of p53 mutant tumours that are resistant to genotoxic damage. Questions surround why this response is so delayed and how its mechanisms serve a survival function. After uncoupling apoptosis from G1 and S phase arrests and adapting these checkpoints, p53 mutated tumour cells arrive at the G2 compartment where decisions regarding survival and death

Jekaterina Erenpreisa; M S Cragg



The ultrastructure of mitotic nuclei of Blastocrithidia triatomae  

Microsoft Academic Search

The fine structure of mitotic nuclei of the flagellateBlastocrithidia triatomae has been studied by serial thin sections and three-dimensional reconstructions. The sequence of changes during the four stages of mitosis are described. A set of three dense plaques is constantly found in the equatorial stage of mitosis. The microtubular spindle is organized around these plaques. The plaques split into halves

Alberto J. Solari



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




Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis  

Microsoft Academic Search

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

Mary Ellen Moynahan; Maria Jasin



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

SciTech Connect

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

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



Apoptosis Resistance and PKC Signaling: Distinguishing Features of High and Low Metastatic Cells12  

PubMed Central

The complexity of the process of metastasis is widely recognized. We report herein on a recurrent feature of high compared to low metastatic cells that is linked to their ability to survive early after their arrival at secondary sites. Using novel fluorescent-based imaging strategies that assess tumor cell interaction with the lung microenvironment, we have determined that most high and low metastatic cells can be distinguished within 6 hours of their arrival in the lung and further that this difference is defined by the ability of high metastatic cells to resist apoptosis at the secondary site. Despite the complexity of the metastatic cascade, the performance of cells during this critical window is highly defining of their metastatic proclivity. To explore mechanisms, we next evaluated biochemical pathways that may be linked to this survival phenotype in highly metastatic cells. Interestingly, we found no association between the Akt survival pathway and this metastatic phenotype. Of all pathways examined, only protein kinase C (PKC) activation was significantly linked to survival of highly metastatic cells. These data provide a conceptual understanding of a defining difference between high and low metastatic cells. The connection to PKC activation may provide a biologic rationale for the use of PKC inhibition in the prevention of metastatic progression. PMID:22496624

Hong, Sung-Hyeok; Ren, Ling; Mendoza, Arnulfo; Eleswarapu, Ananth; Khanna, Chand



A Partitioning Based Adaptive Method for Robust Removal of Irrelevant Features from High-dimensional Biomedical Datasets  

PubMed Central

We propose a novel method called Partitioning based Adaptive Irrelevant Feature Eliminator (PAIFE) for dimensionality reduction in high-dimensional biomedical datasets. PAIFE evaluates feature-target relationships over not only a whole dataset, but also the partitioned subsets and is extremely effective in identifying features whose relevancies to the target are conditional on certain other features. PAIFE adaptively employs the most appropriate feature evaluation strategy, statistical test and parameter instantiation. We envision PAIFE to be used as a third-party data pre-processing tool for dimensionality reduction of high-dimensional clinical datasets. Experiments on synthetic datasets showed that PAIFE consistently outperformed state-of-the-art feature selection methods in removing irrelevant features while retaining relevant features. Experiments on genomic and proteomic datasets demonstrated that PAIFE was able to remove significant numbers of irrelevant features in real-world biomedical datasets. Classification models constructed from the retained features either matched or improved the classification performances of the models constructed using all features. PMID:22779051

Liu1, Guodong; Kong, Lan; Gopalakrishnan, Vanathi



Characteristic features of topside ionograms in the high-latitude ionosphere.  

NASA Astrophysics Data System (ADS)

Topside ionograms display a multitude of specific features in the high-latitude regions. In this report we present an analysis of these features based upon topside ionograms of the Kosmos-1809 satellite taken in May-June 1987. These ionograms were received onboard icebreaker Sibir during a polar expedition in this time. Since the ionograms were downlinked directly in the time of sounding, they were not strongly curtailed to fit the limited onboard memory and thus were much more informative. Acquiring the data in such way allowed us to see little-studied and even unknown ionogram features. Among them we note traces of a characteristic form which were interpreted earlier as signal reflections from almost vertical walls with increased electron density. Such structures are typical for the auroral oval ionosphere. To interpret this features we used a technique of ray trajectory synthesis. We present a sequence of ionograms with all phases of closing to, flying through and away from a higher-density wall. Quite often one find on the polar ionograms broad-band noise signals in different frequency ranges. On the ionograms they are seen as frequency-limited vertical columns from the very top of the ionogram to its bottom. Low-frequency noise (0.3-0.8 MHz) appear during auroral oval fly-throughs and are interpreted as a result of auroral kilometric radiation (AKR). Narrow bands on the magnetic gyrofrequency and upper hybrid frequency could be understood as an ionospheric plasma resonance response near the radiating antenna. Also, there are strong noises in the 3-5 MHz which we were not able to interpret. During some sounding sessions the transmitter was turned off so it was possible to record only natural and artificial noises and separate them from the ionospheric sounding responses.

Panshin, Evgeniy; Danilkin, Nick; Tsybulya, Konstantin; Zhuravliov, Sergey


A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization.  

PubMed Central

The fission yeast dsk1+ gene, a multicopy suppressor for cold-sensitive dis1 mutants, encodes a novel 61-kd protein kinase. It is a phosphoprotein, and phosphoserine is the major phosphorylated amino acid. Hyperphosphorylation of dsk1 causes a mobility shift, resulting in two dsk1-specific protein bands. The phosphorylation pattern is strikingly altered when cell cycle progression is delayed or arrested. The slowly migrating phosphorylated form is prominent in mitotically arrested cells, and the fast migrating form is enriched in interphase-arrested cells. dsk1 is a protein kinase. It auto-phosphorylates as well as phosphorylates myelin basic protein (MBP). Phosphotyrosine as well as phosphoserine/threonine were found in autophosphorylation, but no tyrosine phosphorylation occurs when MBP was used as the substrate. The dsk1 immunoprecipitates from mitotically arrested cells have a several-fold higher kinase activity than that from wild type. The haploid gene disruptant is viable, indicating that the dsk1+ gene is non-essential for viability. High dosage of dsk1+, however, strongly delays the G2/M progression. Immunofluorescence microscopy using anti-dsk1 antibody shows that localization pattern of dsk1 protein strikingly alters depending on cell cycle stages. In G2-arrested cells, dsk1 locates in the cytoplasm, whereas in mitotically arrested cells, nuclear stain is intense. In wild-type cells, nuclear stain is seen only in mitotic cells. Hence dsk1 protein may play an important role in mitotic control by altering cellular location, degree of phosphorylation and kinase activity. We discuss possible roles of dsk1 kinase as an add-on regulator in mitosis. Images PMID:8485317

Takeuchi, M; Yanagida, M



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



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


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



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



Automatic Genre Classification Using Large High-Level Musical Feature Sets  

Microsoft Academic Search

This paper presents a system that extracts 109 musical features from symbolic recordings (MIDI, in this case) and uses them to classify the recordings by genre. The features used here are based on instrumentation, texture, rhythm, dynamics, pitch statistics, melody and chords. The classification is performed hierarchically using different sets of features at different levels of the hierarchy. Which features

Cory Mckay; Ichiro Fujinaga



Synthesis and Biological Evaluation of Optimized Inhibitors of the Mitotic Kinesin Kif18A.  


The mitotic spindle, a highly dynamic structure composed of microtubules, mediates the segregation of the previously duplicated genome into the two nascent daughter cells. Errors in this process contribute to pathology including tumor formation. Key for the shape and function of the mitotic spindle are kinesins, molecular motor proteins that convert chemical energy into mechanical work. Due to their fast mode of action, small molecules are valuable tools to dissect the dynamic functions of kinesins during mitosis. In this study, we report the identification of optimized small molecule inhibitors of the mitotic kinesin Kif18A. Using BTB-1, the first identified Kif18A inhibitor, as a lead compound, we synthesized a collection of derivatives. We demonstrate that some of the synthesized derivatives potently inhibited the ATPase activity of Kif18A with a half maximal inhibitory concentration (IC50) value in the low micromolar range. In vitro analysis of a panel of Kif18A-related kinesins revealed that the two most potent compounds show improved selectivity compared to BTB-1. Structure-activity relationship studies identified substituents mediating undesired inhibitory effects on microtubule polymerization. In summary, our study provides key insights into the mechanism of action of BTB-1 and its analogs, which will have a great impact on the further development of highly selective and bioactive Kif18A inhibitors. Since Kif18A is frequently overexpressed in solid tumors, such compounds are not only of great interest for basic research but also have the potential to open up new strategies for the treatment of human diseases. PMID:25402598

Braun, Joachim; Möckel, Martin M; Strittmatter, Tobias; Marx, Andreas; Groth, Ulrich; Mayer, Thomas U



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)



A new segmentation technique for brain and head from high resolution MR image using unique histogram features  

Microsoft Academic Search

This paper presents a high resolution MR image acquisition protocol for better visualization of normal gray structures of brain, a unique feature of the histogram of the reconstructed images of this protocol, an automated segmentation algorithm of the head contour and the entire brain by using this feature. Using signal nulling effect we have emphasized enhancing the intensity difference between

Somojit Saha; Sarit Kumar Das; Avijit Kar



High Levels of KAP1 Expression Are Associated with Aggressive Clinical Features in Ovarian Cancer  

PubMed Central

KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (?2 = 14.57, p < 0.0001), pathological grade (?2 = 6.06, p = 0.048) and metastases (?2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230–0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer. PMID:25548895

Cui, Yanfen; Yang, Shaobin; Fu, Xin; Feng, Jingwen; Xu, Shilei; Ying, Guoguang



High Levels of KAP1 Expression Are Associated with Aggressive Clinical Features in Ovarian Cancer.  


KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (?2 = 14.57, p < 0.0001), pathological grade (?2 = 6.06, p = 0.048) and metastases (?2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230-0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer. PMID:25548895

Cui, Yanfen; Yang, Shaobin; Fu, Xin; Feng, Jingwen; Xu, Shilei; Ying, Guoguang



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




SciTech Connect

We present the detection of multiple high-velocity silicon monoxide (SiO v = 1, 2, J = 1-0) maser features in the high-mass protostar W51 North which are distributed over an exceedingly large velocity range from 105 to 230 km s{sup -1}. The SiO v = 1, J = 1-0 maser emission shows 3-5 narrow components which span a velocity range from 154 to 230 km s{sup -1} according to observational epochs. The SiO v = 2, J = 1-0 maser also shows 3-5 narrow components that do not correspond to the SiO v = 1 maser and span a velocity range from 105 to 154 km s{sup -1}. The multiple maser components show significant changes on very short timescales (<1 month) from epoch to epoch. We suggest that the high-velocity SiO masers may be emanated from massive star-forming activity of the W51 North protostar as SiO maser jets and will be a good probe of the earliest evolutionary stages of high-mass star formation via an accretion model. Further high angular resolution observations will be required for confirmation.

Cho, Se-Hyung; Kim, Jaeheon; Byun, Do-Young, E-mail:, E-mail:, E-mail: [Korean VLBI Network, Korea Astronomy and Space Science Institute, P. O. Box 88, Yonsei University, Seongsan-ro 262, Seodaemun, Seoul 120-749 (Korea, Republic of)



High-speed smart camera with embedded feature extractions and profilometry measurements  

NASA Astrophysics Data System (ADS)

Nowadays, high-speed imaging offers high investigation possibilities for a wide variety of applications such as motion study, manufacturing developments. Moreover, due to the electronic progresses, real-time processing can be implemented in the high-speed acquisition systems. Important information can be extracted in real-time from the image and then be used for on-line controls. Therefore we have developed a high-speed smart camera with high-speed CMOS sensor, typically 500 fps with a 1.3 Mega-pixels resolution. Different specific processing have been implemented inside an embedded FPGA according to the high-speed data-flow. The processing are mainly dedicated to feature extraction such as edge detection, or image analysis, and finally markers extraction and profilometry. In any case, the data processing allows to reduce the large data flow (6.55 Gbps) and to propose a transfer on a simple serial output link as USB 2.0. This paper presents the high-speed smart camera and focuses two processing implementations: the marker extraction and the related profilometry measurement. In the marker extraction mode, the center of mass is determined for each marker by a combination of image filtering. Only the position of the center is transferred via the USB 2.0 link. For profilometry measurements, a simplify algorithm has been implemented at low-cost in term of hardware resources. The positions of the markers or the different object's profiles can be determined in real-time at 500 fps with full resolution image. A higher image rate can be reached with a lower resolution (i.e. 500 000 profiles for a single row image).

Dubois, J.; Mosqueron, R.; Paindavoine, M.; Beguin, F.; Clerc, C.; Khattab, K.



A Hybrid Feature Subset Selection Algorithm for Analysis of High Correlation Proteomic Data  

PubMed Central

Pathological changes within an organ can be reflected as proteomic patterns in biological fluids such as plasma, serum, and urine. The surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS) has been used to generate proteomic profiles from biological fluids. Mass spectrometry yields redundant noisy data that the most data points are irrelevant features for differentiating between cancer and normal cases. In this paper, we have proposed a hybrid feature subset selection algorithm based on maximum-discrimination and minimum-correlation coupled with peak scoring criteria. Our algorithm has been applied to two independent SELDI-TOF MS datasets of ovarian cancer obtained from the NCI-FDA clinical proteomics databank. The proposed algorithm has used to extract a set of proteins as potential biomarkers in each dataset. We applied the linear discriminate analysis to identify the important biomarkers. The selected biomarkers have been able to successfully diagnose the ovarian cancer patients from the noncancer control group with an accuracy of 100%, a sensitivity of 100%, and a specificity of 100% in the two datasets. The hybrid algorithm has the advantage that increases reproducibility of selected biomarkers and able to find a small set of proteins with high discrimination power. PMID:23717808

Kordy, Hussain Montazery; Baygi, Mohammad Hossein Miran; Moradi, Mohammad Hassan



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


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. PMID:25257552

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



Subresolution assist feature implementation for high-performance logic gate-level lithography  

NASA Astrophysics Data System (ADS)

This paper investigates the implementation of sub-resolution assist features (SRAFs) in high performance logic designs for the poly-gate conductor level. We will discuss the concepts used for SRAF rule generation, SRAF data preparation and what we term "binary" optical proximity correction (OPC) to prevent catastrophic line-width problems. Lithographic process window (PW) data obtained with SRAFs will be compared to PW data obtained without SRAF. SRAM cells are shown printed with annular illumination and SRAFs, for both the 130 nm and 100 nm logic nodes as defined by the International Technology Roadmap for Semiconductors (ITRS). This study includes a comparison of the experimental results of SRAMs printed from designs corrected with rule-based OPC to those printed from designs corrected with model-based OPC.

Gabor, Allen H.; Bruce, James A.; Chu, William; Ferguson, Richard A.; Fonseca, Carlos A.; Gordon, Ronald L.; Jantzen, Kenneth R.; Khare, Mukesh; Lavin, Mark A.; Lee, Woo-Hyeong; Liebmann, Lars W.; Muller, Karl P.; Rankin, Jed H.; Varekamp, Patrick; Zach, Franz X.



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

SciTech Connect

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

Ji Hongjun [Harbin Institute of Technology Shenzhen Graduate School, HIT Campus, Shenzhen University Town, Xili, Shenzhen 518055 (China); State Key Laboratory of Advanced Welding Production Technology, Harbin Institute of Technology, 92, Xidazhi Street, Nangang, Harbin 150001 (China); Li Mingyu [Harbin Institute of Technology Shenzhen Graduate School, HIT Campus, Shenzhen University Town, Xili, Shenzhen 518055 (China)], E-mail:; Kim, Jong-Myung; Kim, Dae-Won [Jeonnam Provincial College, Jeonnam 517-802 (Korea, Republic of); Wang Chunqing [State Key Laboratory of Advanced Welding Production Technology, Harbin Institute of Technology, 92, Xidazhi Street, Nangang, Harbin 150001 (China)



Design features of a high-intensity, cesium-sputter/plasma-sputter negative ion source  

SciTech Connect

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

Alton, G.D.; Mills, G.D. [Oak Ridge National Lab., TN (United States); Dellwo, J. [ORNL and Joint Institute for Heavy Ion Research, Oak Ridge, TN (United States)



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



A molecular mechanism of mitotic centrosome assembly in Drosophila.  


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

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



Simultaneous Evolution of Feature Subset and Neural Classifier on High-Dimensional Data  

Microsoft Academic Search

This paper describes a novel feature selection algorithm which utilises a genetic algorithm to simultaneously optim - ise a feature subset and the weights for a three-layer feed- forward neural network classifier. On the \\

Jennifer Hallinan; Paul Jackway



High resolution (SE-I) scanning electron microscopy features of primate cerebellar cortex.  


This paper provides an exploration into the outer and inner surfaces of primate cerebellar neurons using secondary electron-I (SE-I) topographic contrast. SE-I enriched, chromium coated, cryofractured cerebellum staged within the condenser/objective lens stage of SEMs, equipped with high brightness LaB6 and field emission emitter, generated quality images of intact and fractured nerve cells studied at intermediate and high magnifications. Granule and Golgi cell surfaces revealed smooth, accurately delineated profiles of the true cell surface features, which lacked the SE-III dominated brilliance of conventional gold or gold-palladium decorated images. Fractured non synaptic segments of parallel fibers in the molecular layer showed interconnected anastomotic networks of ER tubules, vesicles and cisterns, whereas cross fractured presynaptic "en passant" endings of these fibers exhibited spheroidal synaptic vesicles and SE-I edge brightness contrast delineated their limiting plasma membranes. Parallel fiber fractured synaptic endings showed a homogeneous extravesicular material surrounding the synaptic vesicles. The neuroglial cytoplasm ensheathing nerve processes exhibited a smooth discontinuous surface. The high mass density surface of the myelin sheath showed a mixed population of globular structures, 10-30 nm, corresponding to protein and phospholipid microdomains. PMID:7873989

Castejón, O J; Castejón, H V; Apkarian, R P



Magnetic-field-induced microstructural features in a high carbon steel during diffusional phase transformation  

NASA Astrophysics Data System (ADS)

In this work, a high purity, high carbon steel was heat treated without and with a 12-T magnetic field. The microstructural features induced by magnetic field during its diffusion-controlled austenite decomposition were investigated by means of optical microscopy and SEM/EBSD. It is found that the magnetic field increases the amount of the abnormal structure, which is composed of proeutectoid cementite along the prior austenite boundaries and ferrite around it, because magnetic field increases the austenite grain size and promotes the transformation of carbon-depleted austenite to ferrite. No specific orientation relationship between abnormal ferrite and cementite has been found in the non-field- or the field-treated specimens. Magnetic field evidently promotes the spheroidization of pearlite, due to its effect of enhancing carbon diffusion through raising the transformation temperature and its effect of increasing the relative ferrite/cementite interface energy. As magnetic field favors the nucleation of the high magnetization phase-pearlitic ferrite, the occurrence of the P-P2 OR that corresponds to the situation that ferrite nucleates prior to cementite during pearlitic transformation is enhanced by the magnetic field.

Zhang, Xiaoxue; Zhang, Yudong; Gong, Minglong; Esling, Claude; Zhao, Xiang; Zuo, Liang



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

Microsoft Academic Search

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

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



Mitotic activity in dorsal epidermis of Rana pipiens.  

NASA Technical Reports Server (NTRS)

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

Garcia-Arce, H.; Mizell, S.



Prioritizing spatial accuracy in high-resolution fMRI data using multivariate feature weight mapping  

PubMed Central

Although ultra-high-field fMRI at field strengths of 7T or above provides substantial gains in BOLD contrast-to-noise ratio, when very high-resolution fMRI is required such gains are inevitably reduced. The improvement in sensitivity provided by multivariate analysis techniques, as compared with univariate methods, then becomes especially welcome. Information mapping approaches are commonly used, such as the searchlight technique, which take into account the spatially distributed patterns of activation in order to predict stimulus conditions. However, the popular searchlight decoding technique, in particular, has been found to be prone to spatial inaccuracies. For instance, the spatial extent of informative areas is generally exaggerated, and their spatial configuration is distorted. We propose the combination of a non-parametric and permutation-based statistical framework with linear classifiers. We term this new combined method Feature Weight Mapping (FWM). The main goal of the proposed method is to map the specific contribution of each voxel to the classification decision while including a correction for the multiple comparisons problem. Next, we compare this new method to the searchlight approach using a simulation and ultra-high-field 7T experimental data. We found that the searchlight method led to spatial inaccuracies that are especially noticeable in high-resolution fMRI data. In contrast, FWM was more spatially precise, revealing both informative anatomical structures as well as the direction by which voxels contribute to the classification. By maximizing the spatial accuracy of ultra-high-field fMRI results, global multivariate methods provide a substantial improvement for characterizing structure-function relationships. PMID:24795548

Buschmann, Tilo; Lohmann, Gabriele; Margulies, Daniel S.; Trampel, Robert; Turner, Robert



SUMOylation inhibits FOXM1 activity and delays mitotic transition.  


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



Mitotic Exit in the Absence of Separase Activity  

PubMed Central

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

Lu, Ying



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

PubMed Central

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



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.



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



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



High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment  

PubMed Central

High altitude pulmonary edema (HAPE) is a noncardiogenic pulmonary edema which typically occurs in lowlanders who ascend rapidly to altitudes greater than 2500-3000 m. Early symptoms of HAPE include a nonproductive cough, dyspnoea on exertion and reduced exercise performance. Later, dyspnoea occurs at rest. Clinical features are cyanosis, tachycardia, tachypnoea and elevated body temperature generally not exceeding 38.5°C. Rales are discrete initially and located over the middle lung fields. HAPE mainly occurs due to exaggerated hypoxic pulmonary vasoconstriction and elevated pulmonary artery pressure. It has been observed that HAPE is a high permeability type of edema occurring also due to leaks in the capillary wall (‘stress failure’). Slow descent is the most effective method for prevention; in addition, graded ascent and time for acclimatization, low sleeping altitudes, avoidance of alcohol and sleeping pills, and avoidance of exercise are the key to preventing HAPE. Treatment of HAPE consists of immediate improvement of oxygenation either by supplemental oxygen, hyperbaric treatment, or by rapid descent. PMID:23580834

Paralikar, Swapnil J.



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



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



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

NASA Technical Reports Server (NTRS)

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

Volk, Kevin; Kwok, Sun; Hrivnak, Bruce



Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control.  


Advanced human cancers are invariably aneuploid, in that they harbour cells with abnormal chromosome numbers. However, the molecular defects underlying this trait, and whether they are a cause or a consequence of the malignant phenotype, are not clear. Mutations that disable the retinoblastoma (Rb) pathway are also common in human cancers. These mutations promote tumour development by deregulating the E2F family of transcription factors leading to uncontrolled cell cycle progression. We show that the mitotic checkpoint protein Mad2 is a direct E2F target and, as a consequence, is aberrantly expressed in cells with Rb pathway defects. Concordantly, Mad2 is overexpressed in several tumour types, where it correlates with high E2F activity and poor patient prognosis. Generation of Rb pathway lesions in normal and transformed cells produces aberrant Mad2 expression and mitotic defects leading to aneuploidy, such that elevated Mad2 contributes directly to these defects. These results demonstrate how chromosome instability can arise as a by-product of defects in cell cycle control that compromise the accuracy of mitosis, and suggest a new model to explain the frequent appearance of aneuploidy in human cancer. PMID:15306814

Hernando, Eva; Nahlé, Zaher; Juan, Gloria; Diaz-Rodriguez, Elena; Alaminos, Miguel; Hemann, Michael; Michel, Loren; Mittal, Vivek; Gerald, William; Benezra, Robert; Lowe, Scott W; Cordon-Cardo, Carlos



Release of mitotic descendants by giant cells from irradiated Burkitt's lymphoma cell line..  


Polyploid giant cells are produced as part of the response of p53 mutant Burkitt's lymphoma cell lines to high doses of irradiation. Polyploid giant cells arise by endo-reduplication in the first week after a single 10 Gray dose of irradiation. Within the giant cells a sub-nuclear structure is apparent and within this, sub-nuclear autonomy is evident, as displayed by independent nuclear structure and DNA replication in different parts of the nucleus. The majority of these cells soon die as apoptotic polykaryons. However, approximately 10-20% of giant cells remain viable into the second week after irradiation and begin vigorous extrusion of large degraded chromatin masses. During the second week, the giant cells begin to reconstruct their nuclei into polyploid 'bouquets', where chromosome double-loops are formed. Subsequently, the bouquets return to an interphase state and separate into several secondary nuclei. The individual sub-nuclei then resume DNA synthesis with mitotic divisions and sequester cytoplasmic territories around themselves, giving rise to the secondary cells, which continue mitotic propagation. This process of giant cell formation, reorganization and breakdown appears to provide an additional mechanism for repairing double-strand DNA breaks within tumour cells. PMID:10964453

Erenpreisa, J A; Cragg, M S; Fringes, B; Sharakhov, I; Illidge, T M



Titanium dioxide nanoparticles induce cytotoxicity and reduce mitotic index in human amniotic fluid-derived cells.  


Titanium dioxide (TiO2) nanoparticles (NPs) are commonly used materials present in many consumables for which most people are exposed to. The biological hazards of the NPs on human health have been demonstrated previously. In this study, we aimed to assess the cytotoxicity potency of TiO2 NPs on the primary human amniotic fluid cells. The cells derived from amniotic fluid were treated with different dosages of TiO2 NPs for some periods. Cell adhesion status was assessed using a light microscopic observation. Cell proliferation and cell death rates were determined using trypan blue staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Also, mitotic index was determined using fluorescence in situ hybridization with chromosome 8 centromer-specific DNA probe. Disrupted cell adhesion, decreased proliferation, and increased mortality rates were detected in the cells that were treated with TiO2 NPs depending on the dosage (p < 0.001). Also, reduced mitotic index was determined in the cells depending on the time and TiO2 dosage when compared with the controls (p < 0.0001). These results showed that TiO2 NPs have high cytotoxicity for amniotic fluid-derived cells. Therefore, different products containing TiO2 NPs should be used with care, especially for pregnant women. PMID:24717318

Acar, Ms; Bulut, Zb; Ate?, A; Nami, B; Koçak, N; Y?ld?z, B



Active DNA Demethylation in Post-Mitotic Neurons: A Reason for Optimism  

PubMed Central

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 into 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.



Intracellular Targets for a Phosphotyrosine Peptidomimetic include the Mitotic Kinesin, MCAK  

PubMed Central

SH2 domains are attractive targets for chemotherapeutic agents due to their involvement in the formation of protein-protein interactions critical to many signal transduction cascades. Little is known, however, about how synthetic SH2 domain ligands would influence the growth properties of tumor cells or with which intracellular proteins they would interact due to their highly charged nature and enzymatic lability. In this study, a prodrug delivery strategy was used to introduce an enzymatically stable, phosphotyrosine peptidomimetic into tumor cells. When tested in a human tumor cell panel, the prodrug exhibited a preference for inhibiting the growth of leukemia and lymphoma cells. In these cells, it was largely cytostatic and induced endoreduplication and the appearance of midbodies. Proteomic analyses identified multiple targets that included mitotic centromere-associated kinesin (MCAK). Molecular modeling studies suggested the ATP-binding site on MCAK as the likely site of drug interaction. Consistent with this, ATP inhibited the drug-MCAK interaction and the drug inhibited MCAK ATPase activity. Accordingly, the effects of the prodrug on the assembly of the mitotic spindle and alignment of chromosomes were consistent with the identification of MCAK as an important intracellular target. PMID:23830822

Huang, Rong; Oh, Hyunju; Arrendale, Allison; Martin, Victoria A.; Galan, Jacob; Workman, Eric J.; Stout, Jane R.; Walczak, Claire E.; Tao, W. Andy; Borch, Richard F.; Geahlen, Robert L.



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


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

Morales, Alfredo M. (Pleasanton, CA)



Enhancement of spontaneous mitotic recombination by the meiotic mutant spo11-1 in Saccharomyces cerevisiae  

SciTech Connect

Both nonreciprocal and reciprocal mitotic recombination are enhanced by the recessive mutant spo11-1, which was previously shown to affect meiosis by decreasing recombination and increasing nondisjunction. The mitotic effects are not distributed equally in all chromosomal regions. The genotypes of mitotic recombinants in spo11-1/spo11-1 diploid cells provide further evidence that widely spaced chromosomal markers undergo coincident conversion in mitosis.

Bruschi, C.V.; Esposito, M.S.



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


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



Multi-feature statistical nonrigid registration using high-dimensional generalized information measures.  


Nonrigid image registration methods based on the optimization of information-theoretic measures provide versatile solutions for robustly aligning mono-modal data with nonlinear variations and multi-modal data in radiology. Whereas mutual information and its variations arise as a first choice, generalized information measures offer relevant alternatives in specific clinical contexts, Their usual application setting is the alignement of image pairs by statistically matching scalar random variables (generally, greylevel distributions), handled via their probability densities. In this paper, we address the issue of estimating and optimizing generalized information measures over high-dimensional state spaces to derive multi-feature statistical nonrigid registration models. Specifically, we introduce novel consistent and asymptotically unbiaised kappa nearest neighbors estimators of alpha-informations, and study their variational optimization over finite and infinite dimensional smooth transform spaces. The resulting theoretical framework provides a well-posed and computationally efficient alternative to entropic graph techniques. Its performances are assessed on two cardiological applications: measuring myocardial deformations in tagged MRI, and compensating cardio-thoracic motions in perfusion MRI. PMID:22003658

Hamrouni, Sameh; Rougon, Nicolas; Prêteux, Françoise



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

NASA Astrophysics Data System (ADS)

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

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



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

NASA Astrophysics Data System (ADS)

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

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



Characterization of keratin densities in mitotic WISH cells.  


Three dimensional (3-D) reconstruction of four mitotic WISH cells from ultrathin sections gave an informative representation of the spatial distribution of keratin densities in these cells. The correspondence between the densities as studied by transmission electron microscopy (TEM) and the keratin bodies initially revealed by immunoflourescent colabeling of cultures, was confirmed by immunoelectronmicroscopy. The smaller, and sometimes more elongated densities, were relatively abundant just beneath the subplasmalemmal microfilament band; and at certain levels of the mitotic cell they were observed to be connected to neighboring densities by intact intermediate filaments (IFs). The larger and more spherical densities appeared to be somewhat more discrete and randomly distributed. Other observed associations of the keratin densities included the telophase contractile ring of microfilaments, chromosomes, the reformed telophase nucleus, and desmosomal junctions with neighboring interphase cells. Cytochalasin D (CD) treatment of cells displaced the peripheral keratin densities toward the cell membrane. The density volume constituted 0.52% to 1.57% of the total cell volume, and the proportional density size was decreased in the cells that had progressed into anaphase and telophase. The observed formation and subsequent dissolution of keratin densities during mitosis may represent a dynamic mechanism of restructuring the keratin cytoskeleton in an unpolymerized form in order to allow for rapid reformation of interphase cell junctions. The physical associations observed between intact IFs and the keratin densities may provide support at certain depths of the mitotic cell, and the juxtaposition of densities with nuclear components suggests a possible source of and role for keratin IFs during nuclear events. PMID:7522131

Meek, W D; Henderson, D A



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.



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



Features of idiopathic pulmonary alveolar proteinosis in high resolution computed tomography  

PubMed Central

Summary Background Although the crazy-paving pattern on computed tomography is characteristic for pulmonary alveolar proteinosis (PAP), it is not specific and has not been compared between idiopathic and secondary PAPs in the large studies. The aim of this study was to determine the high resolution computed tomography (HRCT) features of idiopathic PAP. Material/Methods HRCT images of 35 patients (mean age: 38±14years; 54.3% male) with idiopathic PAP (proved by bronchoalveolar lavage or biopsy) were reviewed by two experienced pulmonary radiologist and detailed findings were reported. Results The predominant HRCT presentation of PAP was interlobular septal thickening (ILST;100%) and ground glass opacities (GGOs; 91.7%), resulting in crazy-paving pattern (83%). All patients had diffuse bilateral lung involvement that was symmetric in 97%. ILST and GGO without crazy-paving were seen in 17% and 14.7%, respectively. The overall extent of parenchymal involvement was 50 to 75% in 80% of patients. Thirty three cases (94%) had areas of geographic sparing within the affected lung. Peripheral sparing was seen in 85.7% of patients, including three patterns with some overlap: costophrenic angle (80%), apices (60%), and subpleural (57%) sparing. Other HRCT findings were: consolidation (63%), pulmonary nodules (31.4%), mediastinal and/or hilar lymphadenopathy (23%), mass-like consolidation (17%), pleural effusion (8.6%), and honey combing (5.7%). All female patients (n=16) had crazy-paving, while 13 out of 19 (68%) male patients had crazy-paving on their lung HRCT (p=0.02). Conclusions This study demonstrated that the predominant HRCT presentation of idiopathic PAP was interlobular septal thickening and ground glass opacities, resulting in crazy-paving pattern. PMID:24707326

Mehrian, Payam; Homayounfar, Nasrin; Karimi, Mohammad Ali; Jafarzadeh, Hamid



Surface degradation features and microstructural properties of ultra-high molecular weight polyethylene (UHMWPe).  


Surface degradation of UHMWPe is recognized as a leading clinical concern, limiting the long-term performance in total knee replacements. Eight retrieved tibial plateaux and six wear screening test samples were evaluated for surface degradation features and microstructural features. The surface degradation features were assessed using stereomicroscopy and scanning electron microscopy. Microstructural features were evaluated using optical microscopy of thin cross-sections and a permanganate etching technique. The pitting mechanism of wear was observed on all eight retrieved TKR and covered an average of 12.6% of the surface area. The size of the pits were similar to the size of grains observed in the microstructural evaluation - approximately 100 to 200 microm. The presented observations of pitting in retrieved knee implants have shown that the post-processing microstructure may influence this mechanism of surface degradation and hence the wear products. PMID:15348753

Cornwall, G B; Hansson, C M; Bowe, A J; Bryant, J T



Hybrid (Generalization-Correlation) Method for Feature Selection in High Dimensional DNA Microarray Prediction Problems  

Microsoft Academic Search

\\u000a Microarray data analysis is attracting increasing attention in computer science because of the many applications of machine\\u000a learning methods in prediction problems. The process typically involves a feature selection step, important in order to increase\\u000a the accuracy and speed of the classifiers. This work analyzes the characteristics of the features selected by two wrapper\\u000a methods, the first one based on

Yasel Couce; Leonardo Franco; Daniel Urda; José Subirats; José Jerez


Profiles of US and CT imaging features with a high probability of appendicitis  

PubMed Central

Objectives To identify and evaluate profiles of US and CT features associated with acute appendicitis. Methods Consecutive patients presenting with acute abdominal pain at the emergency department were invited to participate in this study. All patients underwent US and CT. Imaging features known to be associated with appendicitis, and an imaging diagnosis were prospectively recorded by two independent radiologists. A final diagnosis was assigned after 6 months. Associations between appendiceal imaging features and a final diagnosis of appendicitis were evaluated with logistic regression analysis. Results Appendicitis was assigned to 284 of 942 evaluated patients (30%). All evaluated features were associated with appendicitis. Imaging profiles were created after multivariable logistic regression analysis. Of 147 patients with a thickened appendix, local transducer tenderness and peri-appendiceal fat infiltration on US, 139 (95%) had appendicitis. On CT, 119 patients in whom the appendix was completely visualised, thickened, with peri-appendiceal fat infiltration and appendiceal enhancement, 114 had a final diagnosis of appendicitis (96%). When at least two of these essential features were present on US or CT, sensitivity was 92% (95% CI 89–96%) and 96% (95% CI 93–98%), respectively. Conclusion Most patients with appendicitis can be categorised within a few imaging profiles on US and CT. When two of the essential features are present the diagnosis of appendicitis can be made accurately. PMID:20119730

Laméris, W.; van Es, H. W.; ten Hove, W.; Bouma, W. H.; van Leeuwen, M. S.; van Keulen, E. M.; van der Hulst, V. P. M.; Henneman, O. D.; Bossuyt, P. M.; Boermeester, M. A.; Stoker, J.



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: 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



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.



Packaging the Genome: the Structure of Mitotic Chromosomes  

PubMed Central

Mitotic chromosomes are essential structures for the faithful transmission of duplicated genomic DNA into two daughter cells during cell division. Although more than 100 years have passed since chromosomes were first observed, it remains unclear how a long string of genomic DNA is packaged into compact mitotic chromosomes. Although the classical view is that human chromosomes consist of radial 30 nm chromatin loops that are somehow tethered centrally by scaffold proteins, called condensins, cryo-electron microscopy observation of frozen hydrated native chromosomes reveals a homogeneous, grainy texture and neither higher-order nor periodic structures including 30 nm chromatin fibres were observed. As a compromise to fill this huge gap, we propose a model in which the radial chromatin loop structures in the classic view are folded irregularly toward the chromosome centre with the increase in intracellular cations during mitosis. Consequently, compact native chromosomes are made up primarily of irregular chromatin networks cross-linked by self-assembled condensins forming the chromosome scaffold. PMID:17981824

Maeshima, Kazuhiro; Eltsov, Mikhail



Centrosome size sets mitotic spindle length in Caenorhabditis elegans embryos.  


Just as the size of an organism is carefully controlled, the size of intracellular structures must also be regulated. The mitotic spindle is a supramolecular machine that generates the forces which separate sister chromatids during mitosis. Although spindles show little size variation between cells of the same type, spindle length can vary at least 10-fold between different species. Recent experiments on spindle length showed that in embryonic systems spindle length varied with blastomere size. Furthermore, a comparison between two Xenopus species showed that spindle length was dependent on some cytoplasmic factor. These data point toward mechanisms to scale spindle length with cell size. Centrosomes play an important role in organizing microtubules during spindle assembly. Here we use Caenorhabditis elegans to study the role of centrosomes in setting spindle length. We show that spindle length correlates with centrosome size through development and that a reduction of centrosome size by molecular perturbation reduces spindle length. By systematically analyzing centrosome proteins, we show that spindle length does not depend on microtubule density at centrosomes. Rather, our data suggest that centrosome size sets mitotic spindle length by controlling the length scale of a TPXL-1 gradient along spindle microtubules. PMID:20137951

Greenan, Garrett; Brangwynne, Clifford P; Jaensch, Steffen; Gharakhani, Jöbin; Jülicher, Frank; Hyman, Anthony A



Inhibition of mitotic-specific histone phophorylation by sodium arsenite  

SciTech Connect

Synchronized cultures of Chinese hamster cells (line CHO) were used to measure the effects of 10{mu}M sodium arsenite on histone phosphorylation. This treatment caused cell proliferation to be temporarily arrested, after which the cells spontaneously resumed cell proliferation in a radiomimetric manner. Immediately following treatment, it was found that sodium arsenite affected only mitotic-specific HI and H3 phosphorylations. Neither interphase, nor mitotic, H2A and H4 phosphorylations were affected, nor was interphase HI Phosphorylation affected. The phosphorylation of HI was inhibited only in mitosis, reducing HI phosphorylation to 38.1% of control levels, which was the level of interphase HI phosphorylation. The phosphorylation of both H3 variants was inhibited in mitosis, the less hydrophobic H3 to 19% and the more hydrophobic H3 to 24% of control levels. These results suggest that sodium arsenite may inhibite cell proliferation by interfering with the cyclin B/p34{sup cdc2} histone kinase activity which is thought to play a key role in regulating the cell cycle. It has been proposed by our laboratory that HI and H3 phosphorylations play a role in restructuring interphase chromatin into metaphase chromosomes. Interference of this process by sodium arsenite may lead to structurally damaged chromosomes resulting in the increased cancer risks known to be produced by arsenic exposure from the environment.

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



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



Evaluation of the High Latitude Magnetic Conjugacy of Auroral Features Based on DE-1 and Viking Data  

NASA Astrophysics Data System (ADS)

Magnetic Conjugacy studies are of general interest because of their implications concerning the processes that electrically couple the magnetosphere and ionosphere. Early optical studies of auroral conjugacy from the ground and aircraft have shown the general similarity in spatial and temporal development in the Northern and Southern hemispheres, with good conjugacy at minimum activity that decreased with increasing activity. However, few opportunities for simultaneous large-scale imaging in both hemispheres have been available for study. One significant opportunity occurred in 1986 with the overlap in the DE-1 and Viking programs when DE-1 was able to observe the southern hemisphere while Viking was observing the Northern hemisphere. From 48 days of imaging during the March-October time period when coincidences occurred, the morphology of high latitude features during all ranges of activity have been analyzed and when possible compared to IMF data. Four major categorizations seem to occur : 1) clearly conjugate features implying similar topologies and precipitation patterns; 2) conjugate features implying similar topologies, but with distinct differences in precipitation characteristics; 3) features that occur in both hemispheres but at different MLT; and 4) features that appear in only one hemisphere. In this latter category the focus is on large scale (> 500 km) features for which no identifiable counterpoint could be found. The foundation analysis of simultaneous observations is discussed in a companion paper.

Murphree, J. S.; Craven, J. D.



Optical diffraction and high-energy features in three-dimensional photonic crystals F. Garca-Santamara,1,  

E-print Network

Optical diffraction and high-energy features in three-dimensional photonic crystals F. García of the diffraction phenomena observed in three- dimensional photonic crystals. Qualitative and quantitative are now clarified by relating them to diffraction phenom- ena. We also observe an intriguing change

Braun, Paul


Arrested detachment: a DEPDC1B-mediated de-adhesion mitotic checkpoint.  


Mitotic cell rounding is accompanied by changes in the actin cytoskeleton, de-adhesion, and an increase in cortical rigidity. In this issue, Marchesi et al. (2014) describe an adhesion-dependent mitotic checkpoint and identify DEPDC1B as the factor responsible for coordinating de-adhesion with the ability of cells to enter mitosis. PMID:25458006

Garcia-Mata, Rafael




Microsoft Academic Search

The paper presents the influence of hexanitrogen-cobaltiat III of sodiu upon the mitotic division of Allium cepa L. The treatment with hexanitrogen-cobaltiat III of sodiu has determined the lessening of the mitotic index and the chromosomial mutations.The experiment prowed that hexanitrogen-cobaltiat III of sodiu, known as a polluting agent has a mutagenic potential on the plants.



Instantaneous evaluation of mammalian cell culture growth rates through analysis of the mitotic index  

Microsoft Academic Search

Since a culture increases in cell number when dividing cells separate into two newborn cells, the fraction of mitotic cells in a growing cell population directly reflects the overall growth behavior of a cell culture. To rapidly assess the effects of growth conditions on the fraction of mitotic cells we have employed an antibody specific for the phosphorylated form of

Nicholas R Abu-Absi; Friedrich Srienc



Mitotic activity in monkey and rat Leydig cells J.-P. FOUQUET, Marie-Louise KANN  

E-print Network

Mitotic activity in monkey and rat Leydig cells J.-P. FOUQUET, Marie-Louise KANN Laboratoire d of the monkey, Macaca fascicularis, from birth to adulthood and of rats from puberty to adulthood were examined by both light and electron microscopy to estimate the mitotic activity of the Leydig cells. In monkeys

Paris-Sud XI, Université de


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

NASA Astrophysics Data System (ADS)

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

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



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


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



Features of a choice of technical design parameters of combined steam-cycle power unit high-temperature sets  

Microsoft Academic Search

The new high-efficient coal-fired technology based on combinations of Field-Baranovsky and Rankine cycles is proposed. Efficiency of such power units can achieve 48-50 %. Design procedure of CSCPU is developed and the mathematical model taking into account calculation features of high-temperature sets is created. A number of calculations for the power generating units of 25-65 MW are executed. Technical design

K. A. Robertovich



Mitotic catenation is monitored and resolved by a PKC?-regulated pathway  

PubMed Central

Exit from mitosis is controlled by silencing of the spindle assembly checkpoint (SAC). It is important that preceding exit, all sister chromatid pairs are correctly bioriented, and that residual catenation is resolved, permitting complete sister chromatid separation in the ensuing anaphase. Here we determine that the metaphase response to catenation in mammalian cells operates through PKC?. The PKC?-controlled pathway regulates exit from the SAC only when mitotic cells are challenged by retained catenation and this delayed exit is characterized by BubR1-high and Mad2-low kinetochores. In addition, we show that this pathway is necessary to facilitate resolution of retained catenanes in mitosis. When delayed by catenation in mitosis, inhibition of PKC? results in premature entry into anaphase with PICH-positive strands and chromosome bridging. These findings demonstrate the importance of PKC?-mediated regulation in protection from loss of chromosome integrity in cells failing to resolve catenation in G2. PMID:25483024

Brownlow, Nicola; Pike, Tanya; Zicha, Daniel; Collinson, Lucy; Parker, Peter J.



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



Development of a Computational High-Throughput Tool for the Quantitative Examination of Dose-Dependent Histological Features.  


High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT validation was demonstrated by comparison with manual quantitation using liver sections from mice orally gavaged with sesame oil vehicle or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.001-30 ?g/kg) every 4 days for 28 days, which elicits hepatic steatosis with mild fibrosis. A quality control module of QuHAnT reduced the number of quantifiable Oil Red O (ORO)-stained images from 3,123 to 2,756. Increased ORO staining was measured at 10 and 30 ?g/kg TCDD with a high correlation between manual and computational volume densities (Vv ), although the dynamic range of QuHAnT was 10-fold greater. Additionally, QuHAnT determined the size of each ORO vacuole, which could not be accurately quantitated by visual examination or manual point counting. PicroSirius Red quantitation demonstrated superior collagen deposition detection due to the ability to consider all images within each section. QuHAnT dramatically reduced analysis time and facilitated the comprehensive assessment of features improving accuracy and sensitivity and represents a complementary tool for tissue/cellular features that are difficult and tedious to assess via subjective or semiquantitative methods. PMID:25274660

Nault, Rance; Colbry, Dirk; Brandenberger, Christina; Harkema, Jack R; Zacharewski, Timothy R



Spatial Correlation of High Density EMG Signals Provides Features Robust to Electrode Number and Shift in Pattern Recognition for Myocontrol.  


Research on pattern recognition for myoelectric control has usually focused on a small number of EMG channels, because of better clinical acceptability and low computational load with respect to multi-channel EMG. However, recently, high density (HD) EMG technology has substantially improved, also in practical usability, and can thus be applied in myocontrol. HD EMG provides several closely spaced recordings in multiple locations over the skin surface. This study considered the use of HD EMG for controlling upper limb prostheses, based on pattern recognition. In general, robustness and reliability of classical pattern recognition systems are influenced by electrodes shift in dons and doff, and by the presence of malfunctioning channels. The aim of this study was to propose a new approach to attenuate these issues. The HD EMG grid of electrodes is an ensemble of sensors that records data spatially correlated. The experimental variogram, which is a measure of the degree of spatial correlation, was used as feature for classification, contrary to previous approaches that are based on temporal or frequency features. The classification based on the variogram was tested on 7 able-bodied subjects and 1 subject with amputation, for the classification of 9 and 7 classes, respectively. The performance of the proposed approach was comparable with the classic methods based on time-domain and autoregressive features (average classification accuracy over all methods ~95% for 9 classes). However, the new spatial features demonstrated lower sensitivity to electrode shift (±1cm) with respect to the classic features (p<0.05). When even just one channel was noisy, the classification accuracy dropped by ~10% for all methods. However, the new method could be applied without any re-training to a subset of high-quality channels whereas the classic methods require re-training when some channels are omitted. In conclusion, the new spatial feature space proposed in this study improved the robustness to electrode number and shift in myocontrol with respect to previous approaches. PMID:25389242

Stango, Antonietta; Negro, Francesco; Farina, Dario



Absorption features in the 3 micron spectra of highly obscured objects  

NASA Technical Reports Server (NTRS)

Using the IRTF cooled-grating spectrometer moderate resolution 2.4 to 3.8 micron spectra of a selection of IR protostars and one object located behind the Taurus dark cloud were obtained. Two examples of the spectra are presented. It is clear that the absorption near 3.07 micron is dominated by H2O ice and a comparison between the spectra and a simple H2O ice model allows a temperature estimate for the hottest ice-coated grains in these sources. Higher resolution observations showed no indication of the absorption due to the N-H stretching vibration of NH3 near 2.963 micron. The most plausible explanation for the 3.3 and 3.45 micron features appears to be absorption by the mixture of hydrocarbons, although they cannot be identified with features already attributed to hydrocarbons in the ISM, reflection nebulae and Comets. However these features appear the same for all sources in the sample, including Elias 16, thus implying a very similar mixture of molecules in each source.

Smith, Robert G.; Sellgren, Kris; Tokunaga, Alan T.



Abnormal Nuclear Shape in Solid Tumors Reflects Mitotic Instability  

PubMed Central

Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P < 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy. PMID:11141493

Gisselsson, David; Björk, Jonas; Höglund, Mattias; Mertens, Fredrik; Dal Cin, Paola; Åkerman, Måns; Mandahl, Nils



A prognosis based classification of undifferentiated uterine sarcomas: Identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival.  


Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, "Kurihara" diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M?=?36.8, SD?=?5.4) and a low mitotic index group (16 cases, M?=?8.7, SD?=?5.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights. PMID:25130488

Gremel, Gabriela; Liew, Markus; Hamzei, Farzaneh; Hardell, Elin; Selling, Jonas; Ghaderi, Mehran; Stemme, Sten; Pontén, Fredrik; Carlson, Joseph W



Stable aqueous based Cu nanoparticle ink for printing well-defined highly conductive features on a plastic substrate.  


With the aim of inkjet printing highly conductive and well-defined Cu features on plastic substrates, aqueous based Cu ink is prepared for the first time using water-soluble Cu nanoparticles with a very thin surface oxide layer. Owing to the specific properties, high surface tension and low boiling point, of water, the aqueous based Cu ink endows a variety of advantages over conventional Cu inks based on organic solvents in printing narrow conductive patterns without irregular morphologies. It is demonstrated how the design of aqueous based ink affects the basic properties of printed conductive features such as surface morphology, microstructure, conductivity, and line width. The long-term stability of aqueous based Cu ink against oxidation is analyzed through an X-ray photoelectron spectroscopy (XPS) based investigation on the evolution of the surface oxide layer in the aqueous based ink. PMID:21338069

Jeong, Sunho; Song, Hae Chun; Lee, Won Woo; Lee, Sun Sook; Choi, Youngmin; Son, Wonil; Kim, Eui Duk; Paik, Choon Hoon; Oh, Seok Heon; Ryu, Beyong-Hwan



Mitotic asynchrony induces transforming growth factor-?1 secretion from airway epithelium.  


We recently proposed that mitotic asynchrony in repairing tissue may underlie chronic inflammation and fibrosis, where immune cell infiltration is secondary to proinflammatory cross-talk among asynchronously repairing adjacent tissues. Building on our previous finding that mitotic asynchrony is associated with proinflammatory/fibrotic cytokine secretion (e.g., transforming growth factor [TGF]-?1), here we provide evidence supporting cause-and-effect. Under normal conditions, primary airway epithelial basal cell populations undergo mitosis synchronously and do not secrete proinflammatory or profibrotic cytokines. However, when pairs of nonasthmatic cultures were mitotically synchronized at 12 hours off-set and then combined, the mixed cell populations secreted elevated levels of TGF-?1. This shows that mitotic asynchrony is not only associated with but is also causative of TGF-?1 secretion. The secreted cytokines and other mediators from asthmatic cells were not the cause of asynchronous regeneration; synchronously mitotic nonasthmatic epithelia exposed to conditioned media from asthmatic cells did not show changes in mitotic synchrony. We also tested if resynchronization of regenerating asthmatic airway epithelia reduces TGF-?1 secretion and found that pulse-dosed dexamethasone, simvastatin, and aphidicolin were all effective. We therefore propose a new model for chronic inflammatory and fibrotic conditions where an underlying factor is mitotic asynchrony. PMID:24669775

Alcala, Sarah E; Benton, Angela S; Watson, Alan M; Kureshi, Suraiya; Reeves, Erica M K; Damsker, Jesse; Wang, Zuyi; Nagaraju, Kanneboyina; Anderson, Julia; Williams, Aaron M; Lee, Amber J Y; Hayes, Kathleen; Rose, Mary C; Hoffman, Eric P; Freishtat, Robert J



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



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



Object-based gully feature extraction using high spatial resolution imagery  

NASA Astrophysics Data System (ADS)

Gully erosion is responsible for a substantial amount of soil loss and is generally considered an indicator of desertification. Hence, mapping these gully features provides essential information needed on sediment production, identification of vulnerable areas for gully formation, land degradation, and environmental and socio-economical effects. This paper investigates the use of object-oriented image analysis (OOA) to extract gully erosion features from satellite imagery, using a combination of topographic, spectral, shape (geometric) and contextual information obtained from IKONOS and GEOEYE-1 data. A rule-set was developed and tested for a semi-arid to sub-humid region in Morocco. The percentage of gully system area indicated negligible overestimations between the reference area and the OOA area in two sub-watersheds (0.03% and 1.77%). We also observed that finer gully-related edges within the complex gully systems were better identified semi-automatically than was possible by manual digitization, suggesting higher detection accuracy. OOA-based gully mapping is quicker and more objective than traditional methods, and is thus better suited to provide essential information for land managers to support their decision making processes, and for the erosion research community.

Shruthi, Rajesh B. V.; Kerle, Norman; Jetten, Victor



A defect of Kap104 alleviates the requirement of mitotic exit network gene functions in Saccharomyces cerevisiae.  

PubMed Central

A subgroup of the karyopherin beta (also called importin beta) protein that includes budding yeast Kap104 and human transportin/karyopherin beta2 is reported to function as a receptor for the transport of mRNA-binding proteins into the nucleus. We identified KAP104 as a responsible gene for a suppressor mutation of cdc15-2. We found that the kap104-E604K mutation suppressed the temperature-sensitive growth of cdc15-2 cells by promoting the exit from mitosis and suppressed the temperature sensitivity of various mitotic-exit mutations. The cytokinesis defect of these mitotic-exit mutants was not suppressed by kap104-E604K. Furthermore, the kap104-E604K mutation delays entry into DNA synthesis even at a permissive temperature. In cdc15-2 kap104-E604K cells, SWI5 and SIC1, but not CDH1, became essential at a high temperature, suggesting that the kap104-E604K mutation promotes mitotic exit via the Swi5-Sic1 pathway. Interestingly, SPO12, which is involved in the release of Cdc14 from the nucleolus during early anaphase, also became essential in cdc15-2 kap104-E604K cells at a high temperature. The kap104-E604K mutation caused a partial delocalization of Cdc14 from the nucleolus during interphase. This delocalization of Cdc14 was suppressed by the deletion of SPO12. These results suggest that a mutation in Kap104 stimulates exit from mitosis through the activation of Cdc14 and implies a novel role for Kap104 in cell-cycle progression in budding yeast. PMID:12524331

Asakawa, Kazuhide; Toh-e, Akio



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 | 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.



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



Brochothrix thermosphacta Bacteriophages Feature Heterogeneous and Highly Mosaic Genomes and Utilize Unique Prophage Insertion Sites ? †  

PubMed Central

Brochothrix belongs to the low-GC branch of Gram-positive bacteria (Firmicutes), closely related to Listeria, Staphylococcus, Clostridium, and Bacillus. Brochothrix thermosphacta is a nonproteolytic food spoilage organism, adapted to growth in vacuum-packaged meats. We report the first genome sequences and characterization of Brochothrix bacteriophages. Phage A9 is a myovirus with an 89-nm capsid diameter and a 171-nm contractile tail; it belongs to the Spounavirinae subfamily and shares significant homologies with Listeria phage A511, Staphylococcus phage Twort, and others. The A9 unit genome is 127 kb long with 11-kb terminal redundancy; it encodes 198 proteins and 6 tRNAs. Phages BL3 and NF5 are temperate siphoviruses with a head diameter of 56 to 59 nm. The BL3 tail is 270 nm long, whereas NF5 features a short tail of only 94 nm. The NF5 genome (36.95 kb) encodes 57 gene products, BL3 (41.52 kb) encodes 65 products, and both are arranged in life cycle-specific modules. Surprisingly, BL3 and NF5 show little relatedness to Listeria phages but rather demonstrate relatedness to lactococcal phages. Peptide mass fingerprinting of viral proteins indicate programmed ?1 translational frameshifts in the NF5 capsid and the BL3 major tail protein. Both NF5 and BL3 feature circularly permuted, terminally redundant genomes, packaged by a headful mechanism, and integrases of the serine (BL3) and tyrosine (NF5) types. They utilize unique target sequences not previously described: BL3 inserts into the 3? end of a RNA methyltransferase, whereas NF5 integrates into the 5?-terminal part of a putative histidinol-phosphatase. Interestingly, both genes are reconstituted by phage sequence. PMID:20709901

Kilcher, Samuel; Loessner, Martin J.; Klumpp, Jochen



Electronic image stabilization algorithm based on PCA-SIFT feature matching and self-adaptive high-pass filtering  

NASA Astrophysics Data System (ADS)

As the electronic image stabilization (EIS) algorithm based on SIFT feature matching has the problem of complex computation and time consuming, a modified EIS algorithm based on PCA-SIFT feature matching and self-adaptive high-pass filtering is proposed in this paper. Firstly, feature points are extracted by using PCA-SIFT algorithm in reference frame and current frame. And the corresponding points are matched between these two images. Then the Random Sample Consensus (RANSAC) algorithm is used to eliminate the error matching pairs to reduce the influence of local motion in the scene and improve the estimation accuracy of global motion parameters. Finally, the random dithering parameters obtained by self-adaptive high-pass filtering are used to compensate the current frames. And the size of filter is adjusted automatically according to dithering frequency to prevent the overstabilization or understabilization. Experimental results show that the algorithm proposed in this paper can effectively remove vectors caused by random dithering and obtain a stable video.

Li, Min; Wang, BingJian; Yi, Xiang; Hao, Jingya; Wu, Feihong; Qin, Hanlin



Large Erosional Features on the Cascadia Accretionary Wedge Imaged with New High-Resolution Multibeam Bathymetry and Seismic Datasets  

NASA Astrophysics Data System (ADS)

Utilizing new high resolution multibeam bathymetric data along with chirp sub-bottom and multichannel seismic reflection (MCS) data, we identified remarkable erosional features on the toe of the Cascadia accretionary wedge near Willapa Canyon, offshore Washington, USA. Bathymetric data was compiled from the Cascadia Open-Access Seismic Transects (COAST) cruise and from the site survey cruise for the Cascadia Initiative. These features loosely resemble slope failures of the frontal thrust, but can be distinguished from such failures by several key features: They incise the crest of the frontal thrust and encompass the landward limb; They have floors below the level of the abyssal plain, similar to plunge pool morphology; They show no evidence of landslide blocks at the base of the slope indicative of block sliding. The features where likely formed during the latest Pleistocene based on post event deposition, cross-cutting relationships with Juan de Fuca Channel and the Willapa Channel levees and wave field, and post event slip on the frontal thrust of the Cascadia accretionary prism. The Holocene levees of both Willapa Channel and Juan de Fuca Channel overlap these older features, and clearly place an upper bound on the age of the erosional features in the latest Pleistocene. A lower bound is estimated from a sub-bottom profile that images ~30 meters of post scour sediment fill. Using existing literature of Holocene and Pleistocene sedimentation rates we estimate a lower age bound between ~23,000 - 56,000 y.b.p. We also map a fault scarp within the erosional feature, with ~60 m of vertical offset. Using multi-channel seismic reflection profiles from the COAST cruise we interpret this scarp as the surface expression of the landward vergent frontal thrust fault. The apparent short duration of the erosional event along the seaward margin of the accretionary wedge, coupled with the presence of the fresh fault scarp within the erosion zone, are indicative of a dormant feature with significant time required to develop the scarp after cessation of the causative process. Based on morphology, dissimilarity with other submarine features, and available age constraints, we infer that these features were most likely formed during the glacial lake outpouring in the Pacific Northwest known as the Missoula floods which occurred 13,000-19,500 y.b.p. The features themselves bear a strong resemblance to 'coulees' formed during the same glacial events onshore, and the outpourings through Willapa Channel are consistent with previous inferences of the deposition of Missoula Flood deposits in Escanaba Trough. If this timing is correct, the slip rate along the Cascadia frontal thrust can be estimated using fault geometry and scarp height as 2.8 - 4.1 mm/yr.

Beeson, J. W.; Goldfinger, C.



A Selective Overview of Variable Selection in High Dimensional Feature Space  

PubMed Central

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



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


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

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




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: [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)



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)



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



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



MYC High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema  

PubMed Central

Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC. This finding may have implications both for the diagnosis and treatment of these tumors. PMID:20008140

Manner, Johanna; Radlwimmer, Bernhard; Hohenberger, Peter; Mössinger, Katharina; Küffer, Stefan; Sauer, Christian; Belharazem, Djeda; Zettl, Andreas; Coindre, Jean-Michel; Hallermann, Christian; Hartmann, Jörg Thomas; Katenkamp, Detlef; Katenkamp, Kathrin; Schöffski, Patrick; Sciot, Raf; Wozniak, Agnieszka; Lichter, Peter; Marx, Alexander; Ströbel, Philipp



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



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



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

Microsoft Academic Search

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, iodacetate, anthralin, and 12-0-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol,

Bernard A. Kunz; Mohammed A. Hannan; R. H. Haynes



Whole genome functional analysis identifies novel components required for mitotic spindle integrity in human cells  

Microsoft Academic Search

BACKGROUND: The mitotic spindle is a complex mechanical apparatus required for accurate segregation of sister chromosomes during mitosis. We designed a genetic screen using automated microscopy to discover factors essential for mitotic progression. Using a RNA interference library of 49,164 double-stranded RNAs targeting 23,835 human genes, we performed a loss of function screen to look for small interfering RNAs that

Daniel R Rines; Maria Ana Gomez-Ferreria; Yingyao Zhou; Paul DeJesus; Seanna Grob; Serge Batalov; Marc Labow; Dieter Huesken; Craig Mickanin; Jonathan Hall; Mischa Reinhardt; Francois Natt; Joerg Lange; David J Sharp; Sumit K Chanda; Jeremy S Caldwell




Microsoft Academic Search

SUMMARY Mitotic spindles from Chinese hamster ovary (CHO) cells were isolated and purified by a one-step procedure in an isolation medium containing the microtubule-stabilizing drug, taxol. Released mitotic spindles were examined by phase-contrast, polarizing and differential-interference micro- scopy. They were also stained with monoclonal antibody raised against yeast tubulin and examined by epifluorescence microscopy. The spindles were free from visible




A Chromatin-associated Kinesin-related Protein Required for Normal Mitotic Chromosome Segregation in Drosophila  

Microsoft Academic Search

The tiovivo ( tio ) gene of Drosophila encodes a kinesin-related protein, KLP38B , that colocalizes with condensed chromatin during cell division. Wild- type function of the tio gene product KLP38B is re- quired for normal chromosome segregation during mi- tosis. Mitotic cells in tio larval brains displayed circular mitotic figures, increased ploidy, and abnormal anaphase figures. KLP38B mRNA is

Isabel Molina; Sigrid Baars; Julie A. Brill; Karen G. Hales; Margaret T. Fuller; Pedro Ripoll



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


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



High frequency of inflammatory back pain and other features of spondyloarthritis in patients with rheumatoid arthritis.  


The aim of this study was to investigate the frequency of patients with rheumatoid arthritis (RA) who have inflammatory back pain (IBP) and meet the existing classification criteria for ankylosing spondylitis (AS) and spondyloarthritis (SpA). We included 167 patients fulfilling the ACR 1987 revised criteria for RA. After obtaining a medical history and performing a physical examination, standard pelvic X-rays for examination of the sacroiliac joints (SIJ) were ordered in all patients. A computed tomography (CT) or magnetic resonance imaging (MRI) of SIJ was performed in patients with suspected radiographic sacroiliitis and MRI of SIJ in those who have IBP but no radiographic sacroiliitis. IBP was defined according to both Calin and experts' criteria. The modified New York (mNY) criteria were used to classify AS, both ESSG and Amor criteria for SpA and ASAS classification criteria for axial SpA. There were 135 female and 32 male patients with a mean age of 54.8 years. The mean disease duration was 9.8 years. RF was positive in 128 patients (79.2 %) and anti-CCP in 120 patients (81.1 %). Twenty-eight patients with RA (16.8 %) had IBP (Calin criteria), and four (2.4 %) had radiographic sacroiliitis of bilateral grade 3. Three patients (1.8 %) fulfilled the mNY criteria for AS, 31 (18.6 %) ESSG and 26 (15.6 %) Amor criteria for SpA. Nine patients (five with MRI sacroiliitis) (5.3 %) were classified as having axial SpA according to new ASAS classification criteria. This study suggests that the prevalence of SpA features in patients with RA may be much higher than expected. PMID:23129430

Can, Gercek; Solmaz, Dilek; Binicier, Omer; Akar, Servet; Birlik, Merih; Soysal, Ozgul; Akkoc, Nurullah; Manisali, Metin; Onen, Fatos



Raman Spectral Features Associated with Chromophores in High-Yield Pulps  

Microsoft Academic Search

High-yield pulp chromophores are not easily analysed. In Raman spectroscopic studies, advantage can be taken of the fact that chromophores absorb visible light, and they are therefore expected to result in manifestation of the resonance Raman effect. In this effect, the Raman scattering coefficient depends upon the wavelength used to excite the spectrum. The contribution of chromophores in the spectra

Umesh P. Agarwal; Rajai H. Atalla



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.



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

E-print Network

High Accuracy Handwritten Chinese Character Recognition Using Quadratic Abstract We aim to improve the accuracy of handwritten Chi- nese character recognition using two advanced the accuracy significantly, the DLQDF improves only slightly. Compared to the modified quadratic discriminant

Paris-Sud XI, Université de


Cellular analyses of the mitotic region in the Caenorhabditis elegans adult germ line.  


The Caenorhabditis elegans germ line provides a model for understanding how signaling from a stem cell niche promotes continued mitotic divisions at the expense of differentiation. Here we report cellular analyses designed to identify germline stem cells within the germline mitotic region of adult hermaphrodites. Our results support several conclusions. First, all germ cells within the mitotic region are actively cycling, as visualized by bromodeoxyuridine (BrdU) labeling. No quiescent cells were found. Second, germ cells in the mitotic region lose BrdU label uniformly, either by movement of labeled cells into the meiotic region or by dilution, probably due to replication. No label-retaining cells were found in the mitotic region. Third, the distal tip cell niche extends processes that nearly encircle adjacent germ cells, a phenomenon that is likely to anchor the distal-most germ cells within the niche. Fourth, germline mitoses are not oriented reproducibly, even within the immediate confines of the niche. We propose that germ cells in the distal-most rows of the mitotic region serve as stem cells and more proximal germ cells embark on the path to differentiation. We also propose that C. elegans adult germline stem cells are maintained by proximity to the niche rather than by programmed asymmetric divisions. PMID:16672375

Crittenden, Sarah L; Leonhard, Kimberly A; Byrd, Dana T; Kimble, Judith



Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm  

PubMed Central

Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional “compartmentalization” has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial Drosophila embryo on the effective diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of transient mitotic membrane furrows results in a multiscale diffusion effect that has a significant impact on effective diffusion rates across the embryo. Using a combination of live-cell experiments and computational modeling, we characterize these effects and relate effective bulk diffusion rates to instantaneous diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of the early embryo. This multiscale effect may be related to the effect of interphase nuclei on effective diffusion, and thus we propose that an as-yet-unidentified role of syncytial membrane furrows is to temporally regulate bulk embryonic diffusion rates to balance the multiscale effect of interphase nuclei, which ultimately stabilizes the shapes of various morphogen gradients. PMID:22592793

Daniels, Brian R.; Rikhy, Richa; Renz, Malte; Dobrowsky, Terrence M.; Lippincott-Schwartz, Jennifer



Mitotic recombination counteracts the benefits of genetic segregation  

PubMed Central

The ubiquity of sexual reproduction despite its cost has lead to an extensive body of research on the evolution and maintenance of sexual reproduction. Previous work has suggested that sexual reproduction can substantially speed up the rate of adaptation in diploid populations, because sexual populations are able to produce the fittest homozygous genotype by segregation and mating of heterozygous individuals. In contrast, asexual populations must wait for two rare mutational events, one producing a heterozygous carrier and the second converting a heterozygous to a homozygous carrier, before a beneficial mutation can become fixed. By avoiding this additional waiting time, it was shown that the benefits of segregation could overcome a twofold cost of sex. This previous result ignores mitotic recombination (MR), however. Here, we show that MR significantly hastens the spread of beneficial mutations in asexual populations. Indeed, given empirical data on MR, we find that adaptation in asexual populations proceeds as fast as that in sexual populations, especially when beneficial alleles are partially recessive. We conclude that asexual populations can gain most of the benefit of segregation through MR while avoiding the costs associated with sexual reproduction. PMID:17360283

Mandegar, Mohammad A; Otto, Sarah P



Spatial control of mitotic commitment in fission yeast.  


The activation of the Cdk1 (cyclin-dependent kinase 1)-cyclin B complex to promote commitment to mitosis is controlled by the phosphorylation status of the Cdk1 catalytic subunit. Cdk1 phosphorylation by Wee1 kinases blocks activation until Cdc25 (cell division cycle 25) phosphatases remove this phosphate to drive division. Feedback inhibition of Wee1 and promotion of Cdc25 activities by the newly activated Cdk1-cyclin B complexes ensure that the transition from interphase to mitosis is a rapid and complete bi-stable switch. Although this level of molecular understanding of the mitotic commitment switch has been clear for over two decades, it is still unclear how the switch is engaged to promote division at the right time for a particular context. We discuss recent work in fission yeast that shows how the spatial organization of signalling networks, in particular events on the centrosome equivalent, the spindle pole body, plays a key role in ensuring that the timing of cell division is coupled to environmental cues. PMID:24256289

Hagan, Iain M; Grallert, Agnes



Combining multispectral images and selected textural features from high-resolution images to improve discrimination of forest canopies  

NASA Astrophysics Data System (ADS)

Discrimination of vegetation canopies for production of forestry and land use thematic cartography from multispectral satellite images requires high spectral and spatial resolutions, usually not available in this type of images. A methodology is proposed to improve a vegetation oriented classification from a Landsat TM image by adding texture information obtained from panchromatic aerial photographs. Multispectral classification was used to create a mask of the forested areas that was applied over the aerial mosaic composition. Further vegetation classes were defined based on textural differences, and eight texture features derived from the gray level co-occurrence matrix, three textural energy indicators and a factor of edgeness were tested. A selection of optimal features and textural parameters such as number of gray levels, window size and distance between pixels was performed using principal components and stepwise discriminant analysis techniques with a set of representative samples from each class. After a texture segmentation of panchromatic aerial imagery using optimal parameters and features was completed, a post-classification process based on morphological operations was applied to avoid the neighboring effect generated by the texture analysis. Overall accuracy in the identification of texture classes using the four best feathers was 86.6%, while the 88% of accuracy was achieved in the classification of the complete image. This method is useful for discrimination of certain vegetation classes with low spectral separability and arranged in small forest units, increasing the classification detail in those areas of particular interest.

Ruiz, Luis A.; Inan, Igor; Baridon, Juan E.; Lanfranco, Jorge W.



Novel digital diffractive tags integrating anti-counterfeiting, tamper-evident, and high-density WORM data storage features  

NASA Astrophysics Data System (ADS)

Embossed holographic tags for security and anti-counterfeiting applications are being used by industry since many years. However, such elements are not very effective since the detector is usually the human eye, and provides therefore around 80% effective counterfeiting protection of the tag. We present a novel holographic anticounterfeiting technology which provides 99.999% protection against tag counterfeiting. Horus Technologies develops such holographic tags, which include several layers of increasingly secure optical features, from standard visual holographic patterns and OVIDs (Optical Variable Imaging Devices), to micro-holographic text, down to covert features such as encrypted high resolution holographic 1d, 2d and 3d bar codes. We also demonstrate the potential of providing anti-tamper functionality on the same tag, for packaging security (especially for medical packaging). Finally, we demonstrate that more than 1Mb/square mm of digital data can be stored and encrypted on these same tags. A specific low cost laser based reader is developed to read the various security feature of such hybrid universal holographic tags. We also present a way to change and update the encrypted data in the tag in a similar way to RFID tags. Finally, we show a cost effective technique to replicate these structures in volume by roll-to-toll embossing, and even direct by glass molding within the package itself (bottle, vial, etc,..).

Boisdur, Enrick; Kress, Bernard



Interface recombination feature in metal-semiconductor junction at high photo-excitation  

NASA Astrophysics Data System (ADS)

A theory of the photo-induced electromotive force in a p-type semiconductor accounting for the energy band bending and interface recombination dependence on excitation level is developed. It is shown that at high photo-excitation the effective interface recombination velocity in the metal-semiconductor junction is negligible compared with the volume one, when the surface potential is less than its critical value. The photo-induced electromotive force value is maximal at this condition.

Konin, A.



High-resolution seafloor features related to potential gas-hydrate formation off SW Taiwan  

NASA Astrophysics Data System (ADS)

The area off SW Taiwan is considered as a high potential area for gas-hydrate formation. The gas-hydrate signature is indicated by the abundant presence of BSR (Bottom-Simulating-Reflector). High methane concentration is also shown in the bottom water near the seafloor. To have a better understanding, we have conducted deep-towed survey of side-scan sonar and sub-bottom profiler in several potential areas. Pockmarks are found in several places. Some are related to gas seeping. The gas seeps are especially obvious in high-resolution sub-bottom profilers. The high pore-pressure due to the charging of the gas has clearly uplifted a top layer of sediments. The pockmarks area usually accompany the presence of authigenic carbonate. In the image of side-scan sonar data, the irregular patterns of strong backscatter signal are associated with the gas seeping or pockmark sites. The presence of pockmarks or gas seeps could be related to structural faults. Because the NW convergence of the Philippine Sea plate relative to the Eurasian plate, the area off SW Taiwan in fact is under compression and has caused folds and faults. These structural faults provide efficient conduits for fluid to migrate upward. Thus, the pockmarks frequently appear near faults. In the water depth of about 450m, the upward gas even goes into water column and creates clear gas plume image in EK 500 data. The gas is inferred to be dissociated from gas-hydrate and can get into the atmosphere. The dissociation of gas-hydrate has probably also induced the instability of the seafloor off SW Taiwan and cuased submarine landslides.

Hsu, S.; Tsai, C.; Chen, S.; Shih, T.



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

NASA Astrophysics Data System (ADS)

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

Astro-H Science Working Group



Location of 45S Ribosomal Genes in Mitotic and Meiotic Chromosomes of Buthid Scorpions.  


Buthid scorpions exhibit a high variability in diploid number within genera and even within species. Cytogenetically, Buthidae differs from other families of Scorpiones based on its low diploid numbers, holocentric chromosomes, and complex chromosomal chains, which form during meiosis. In this study, we analyzed the distribution of the 45S ribosomal DNA (rDNA) genes in the mitotic and meiotic chromosomes of seven buthid species belonging to the genera Rhopalurus and Tityus with the ultimate goal of elucidating the chromosome organization in these scorpions. The chromosome number ranged from 2n = 6 to 2n = 28. Despite the high variance in diploid number, all species examined carried their 45S rDNA sites in the terminal region of exactly two chromosomes. Analyses of meiotic cells revealed 45S rDNA clusters in the chromosomal chains of Rhopalurus agamemnon, Tityus bahiensis, Tityus confluens, and Tityus martinpaechi, or in bivalent-like configuration in Rhopalurus rochai, Tityus bahiensis, Tityus confluens, Tityus fasciolatus, and Tityus paraguayensis. In the species examined, the 45S rDNA sites colocalized with constitutive heterochromatin regions. In light of the high chromosome variability and maintenance of number and terminal position of 45S rDNA sites in buthids, the heterochromatin may act to conserve the integrity of the ribosomal genes. PMID:25186932

Mattos, Viviane Fagundes; Carvalho, Leonardo Sousa; Cella, Doralice Maria; Schneider, Marielle Cristina



Very compact, high-stability electrostatic actuator featuring contact-free self-limiting displacement  


A compact electrostatic actuator is disclosed for microelectromechanical (MEM) applications. The actuator utilizes stationary and moveable electrodes, with the stationary electrodes being formed on a substrate and the moveable electrodes being supported above the substrate on a frame. The frame provides a rigid structure which allows the electrostatic actuator to be operated at high voltages (up to 190 Volts) to provide a relatively large actuation force compared to conventional electrostatic comb actuators which are much larger in size. For operation at its maximum displacement, the electrostatic actuator is relatively insensitive to the exact value of the applied voltage and provides a self-limiting displacement.

Rodgers, M. Steven (Albuquerque, NM); Miller, Samuel L. (Albuquerque, NM)



Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 increase in UV irradiated cells and during meiosis but not during the mitotic cell cycle.  

PubMed Central

We have examined the transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 in UV irradiated cells, in the mitotic cell cycle, and during meiosis. Levels of RAD18 mRNA increased upon UV irradiation, but remained constant during the mitotic cell cycle. During meiosis, RAD18 mRNA levels rose about 4 fold at a stage coincident with the period when high levels of genetic recombination occur. RAD18 resembles the other DNA repair genes, RAD2, RAD6, RAD7, RAD23, and RAD54, all of which also exhibit increased transcription in response to DNA damage and during meiosis. Comparisons of sequences in 5' flanking regions of RAD genes suggest that different upstream sequences are involved in regulating the expression of DNA repair genes belonging to different epistasis groups. Images PMID:2017370

Jones, J S; Prakash, L



Accurate Matching and Reconstruction of Line Features from Ultra High Resolution Stereo Aerial Images  

NASA Astrophysics Data System (ADS)

In this study, a new reconstruction approach is proposed for the line segments that are nearly-aligned (? 10º) with the epipolar line. The method manipulates the redundancy inherent in line pair-relations to generate artificial 3D point entities and utilize those entities during the estimation process to improve the height values of the reconstructed line segments. The best point entities for the reconstruction are selected based on a newly proposed weight function. To test the performance of the proposed approach, we selected three test patches over a built up area of the city of Vaihingen - Germany. Based on the results, the proposed approach produced highly promising reconstruction results for the line segments that are nearly-aligned with the epipolar line.

Ok, A. O.; Wegner, J. D.; Heipke, C.; Rottensteiner, F.; Soergel, U.; Toprak, V.



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.



Experimental investigation of primary and secondary features in high-mach-number shock-bubble interaction.  


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. PMID:17358611

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



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


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

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



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



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)



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



Immunopathology features of chronic rhinosinusitis in high-altitude dwelling Tibetans  

PubMed Central

Chronic rhinosinusitis (CRS) presents distinct inflammatory and remodeling patterns in different populations and environments. Tibetan ethnic groups live at high altitudes and in cold weather conditions. We sought to examine whether Tibetans exhibit distinct CRS pathology or characteristics. Sinonasal polyps and mucosal tissue were obtained from 14 Tibetan patients with CRS and nasal polyps (CRSwNPs), 13 patients with CRS without nasal polyps (CRSsNPs), and 12 Tibetan controls. Tissue homogenates and serum samples were assayed for several T-helper (TH) cell cytokines and mediators using enzyme linked immunosorbent assay profiles were measured using quantity polymerase chain reaction. Several key inflammatory cells were examined for immunohistochemical markers. CRSwNPs were characterized by increased mediator promoting eosinophilic inflammation (interleukin [IL]-5, eosinophil cationic protein, and total immunoglobulin E) and slight synergism with expression of IL-8, IL-2sRa, IL-1beta, IL-6, and myeloperoxidase, and a predominance of eosinophils, mast cells, and neutrophils. GATA-3 transcription factor was significantly increased and Foxp3 showed a tendency to be impaired in CRSwNPs compared with controls. CRSsNPs were characterized by significantly high levels of transforming growth factor beta1, increased interferon ?, and a significant enhancement of Foxp3 and T-beta compared with CRSwNPs. There were reduced numbers of inflammatory cells but increased levels of macrophages in CRSsNPs. Compared with CRSsNPs, CRSwNPs present a severe inflammatory reaction and show a TH2 milieu with apparently impaired regulatory T cells (Treg) function and increased inflammatory cells infiltration predominated by eosinophilic and mast cells. In contrast, TH1 polarization with enhanced Treg function and increased levels of macrophages appear in CRSsNPs. PMID:24124640

Luo, Ba; Feng, Liu; Jintao, Du; Shixi, Liu; Nan, Zhang; Bachert, Claus



High-Resolution PFPE-based Molding Techniques for Nanofabrication of High-Pattern Density, Sub-20nm Features: A Fundamental Materials Approach  

SciTech Connect

Several perfluoropolyether (PFPE)-based elastomers for high-resolution replica molding applications are explored. The modulus of the elastomeric materials was increased through synthetic and additive approaches while maintaining relatively low surface tension values (<25 mN/m). Using large area (>4 in.{sup 2}) master templates, we experimentally show the relationship between mold resolution and material properties such as modulus and surface tension for materials used in this study. A composite mold approach was used to form flexible molds out of stiff, high modulus materials that allow for replication of sub-20 nm post structures. Sub-100 nm line grating master templates, formed using e-beam lithography, were used to determine the experimental stability of the molding materials. It was observed that as the feature spacing decreased, high modulus PFPE tetramethacrylate (TMA) composite molds were able to effectively replicate the nanograting structures without cracking or tear-out defects that typically occur with high modulus elastomers.

Williams, Stuart S.; Retterer, Scott; Lopez, Rene; Ruiz, Ricardo; Samulski, Edward T.; DeSimone, Joseph M.



A Novel RING Finger Protein, Human Enhancer of Invasion 10, Alters Mitotic Progression through Regulation of Cyclin B Levels  

PubMed Central

The process of cellular morphogenesis is highly conserved in eukaryotes and is dependent upon the function of proteins that are centrally involved in specification of the cell cycle. The human enhancer of invasion clone 10 (HEI10) protein was identified from a HeLa cell library based on its ability to promote yeast agar invasion and filamentation. Through two-hybrid screening, the mitotic cyclin B1 and an E2 ubiquitin-conjugating enzyme were isolated as HEI10-interacting proteins. Mutation of the HEI10 divergent RING finger motif (characteristic of E3 ubiquitin ligases) and Cdc2/cyclin binding and phosphorylation sites alter HEI10-dependent yeast phenotypes, including delay in G2/M transition. In vertebrates, the addition of HEI10 inhibits nuclear envelope breakdown and mitotic entry in Xenopus egg extracts. Mechanistically, HEI10 expression reduces cyclin B levels in cycling Xenopus eggs and reduces levels of the cyclin B ortholog Clb2p in yeast. HEI10 is itself a specific in vitro substrate of purified cyclin B/cdc2, with a TPVR motif as primary phosphorylation site. Finally, HEI10 is itself ubiquitinated in egg extracts and is also autoubiquitinated in vitro. These and other points lead to a model in which HEI10 defines a divergent class of E3 ubiquitin ligase, functioning in progression through G2/M. PMID:12612082

Toby, Garabet G.; Gherraby, Wahiba; Coleman, Thomas R.; Golemis, Erica A.



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


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



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

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



Human papillomavirus type 16 E7 perturbs DREAM to promote cellular proliferation and mitotic gene expression.  


The study of the small DNA tumor viruses continues to provide valuable new insights into oncogenesis and fundamental biological processes. Although much has already been revealed about how the human papillomaviruses (HPVs) can transform cells and contribute to cervical and oropharyngeal cancer, there clearly is much more to learn. In this issue of Oncogene, Pang et al., doi:10.1038/onc.2013.426, demonstrate that the high-risk HPV16 E7 oncogene can promote cellular proliferation by interacting with the DREAM (DP, RB-like, E2F and MuvB) complex at two distinct phases of the cell cycle. Consistent with earlier work, HPV16 E7 can bind to the retinoblastoma tumor suppressor (RB) family member p130 (RBL2) protein and promote its proteasome-mediated destruction thereby disrupting the DREAM complex and can prevent exit from the cell cycle into quiescence. In addition, they demonstrate that HPV16 E7 can bind to MuvB core complex in association with BMYB and FOXM1 and activate gene expression during the G2 and M phase of the cell cycle. Thus, HPV16 E7 acts to prevent exit from the cell cycle entry and promotes mitotic proliferation and may account for the high levels of FOXM1 often observed in poor-risk cervical cancers. PMID:24166507

DeCaprio, J A



Functions of crystallins in and out of lens: roles in elongated and post-mitotic cells.  


The vertebrate lens evolved to collect light and focus it onto the retina. In development, the lens grows through massive elongation of epithelial cells possibly recapitulating the evolutionary origins of the lens. The refractive index of the lens is largely dependent on high concentrations of soluble proteins called crystallins. All vertebrate lenses share a common set of crystallins from two superfamilies (although other lineage specific crystallins exist). The ?-crystallins are small heat shock proteins while the ?- and ?-crystallins belong to a superfamily that contains structural proteins of uncertain function. The crystallins are expressed at very high levels in lens but are also found at lower levels in other cells, particularly in retina and brain. All these proteins have plausible connections to maintenance of cytoplasmic order and chaperoning of the complex molecular machines involved in the architecture and function of cells, particularly elongated and post-mitotic cells. They may represent a suite of proteins that help maintain homeostasis in such cells that are at risk from stress or from the accumulated insults of aging. PMID:24582830

Slingsby, Christine; Wistow, Graeme J



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



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


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

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



Vibrational features of water at the low-density/high-density liquid structural transformations  

NASA Astrophysics Data System (ADS)

A structural transformation in water upon compression was recently observed at the temperature T=277 K in the vicinity of the pressure p?2 000 atm [R.M. Khusnutdinoff, A.V. Mokshin, J. Non-Cryst. Solids 357 (2011) 1677]. 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 detail 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÷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 two distinct modes, where the high-frequency mode is independent of pressure whereas the low-frequency one has the strong, non-monotonic pressure-dependence and exhibits a step-like behavior at the pressure p?2000 atm. The extended analysis of the local structural and vibrational properties discovers that there is a strong correlation between the primary structural and vibrational aspects of the liquid-liquid structural transformation related with the molecular rearrangement within the range of the second coordination shell.

Khusnutdinoff, Ramil M.; Mokshin, Anatolii V.



Freeform mirror fabrication and metrology using a high performance test CGH and advanced alignment features  

NASA Astrophysics Data System (ADS)

The metrology of mirrors with an off-axis aspheric or freeform shape can be based on optical testing using a Computer Generated Hologram as wavefront matching element in an interferometric setup. Since the setup can be understood as optical system consisting of multiple elements with six degrees of freedom each, the accuracy strongly depends on the alignment of the surface under test with respect to the transmission element of the interferometer and the micro optics of the CGH. A novel alignment approach for the relative positioning of the mirror and CGH in six degrees of freedom is reported. In the presented work, a proper alignment is achieved by illuminating alignment elements outside the Clear Aperture (CA) of the optical surface with the help of auxiliary holograms next to the test CGH on the substrate. The peripheral holograms on the CGH substrate are used to generate additional phase maps in the interferogram, that indicate positioning errors. Since the reference spheres represent the coordinate system of the mirror and are measured in the same precision as the optical surface, the registration and shape has to be appropriate to embody the mirrors coordinate system. The alignment elements on the mirror body are diamond machined using freeform turning or micro milling processes in the same machine setup used for the mirror manufacturing. The differences between the turning and milling of alignment lenses is discussed. The novel approach is applied to correct the shape error of a freeform mirror using ultra precision machining. The absolute measurement of the quality of freeform mirror shapes including tilt and optical power is possible using the presented alignment concept. For a better understanding, different metrology methods for aspheres and freeforms are reviewed. To verify the novel method of alignment and the measurement results, the freeform surface is also characterized using ultra high accuracy 2½D profilometry. The results of the different techniques for the absolute measurement of freeforms are compared.

Scheiding, Sebastian; Beier, Matthias; Zeitner, Uwe-Detlef; Risse, Stefan; Gebhardt, Andreas



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


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

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



SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress  

Microsoft Academic Search

We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons.

T Inoue; M Hiratsuka; M Osaki; H Yamada; I Kishimoto; S Yamaguchi; S Nakano; M Katoh; H Ito; M Oshimura



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:; 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)



High-dose radiation employing external beam radiotherapy and high-dose rate brachytherapy with and without neoadjuvant androgen deprivation for prostate cancer patients with intermediate- and high-risk features  

Microsoft Academic Search

The role of neoadjuvant androgen deprivation (NAD) in high-risk prostate cancer patients receiving high-dose radiotherapy (RT) remains unstudied. To evaluate the effect of a course of NAD, we reviewed the experiences of three institutions treating these patients with combined RT and high-dose rate brachytherapy (HDR). Of 1260 prostate cancer patients with high-risk features (pretreatment prostate-specific antigen (PSA) ?10, Gleason Score

C Vargas; A Martínez; R Galalae; J Demanes; A Harsolia; L Schour; N Nuernberg; J Gonzalez



Pyp3 PTPase acts as a mitotic inducer in fission yeast.  

PubMed Central

The p34cdc2 M-phase kinase is regulated by inhibitory phosphorylation of Tyr15, largely through the actions of the p107wee1 tyrosine kinase and p80cdc25 protein tyrosine phosphatase (PTPase). In this study we demonstrate that a second PTPase, encoded by pyp3, also contributes to tyrosyl dephosphorylation of p34cdc2. Pyp3 was identified as a high copy suppressor of a cdc25- mutation. The pyp3 gene encodes a 33 kDa PTPase that is more closely related to human PTP1B and fission yeast pyp1 and pyp2 PTPases than to cdc25. Pyp3 does not share an essential overlapping function with pyp1 or pyp2. We demonstrate that disruption of pyp3 causes a mitotic delay that is greatly exacerbated in cells that are partially defective for cdc25 function and that pyp3 function is essential in cdc25-disruption wee1- strains. Pyp3 PTPase effectively dephosphorylates and activates the p34cdc2 kinase in vitro. We conclude that the pyp3 PTPase acts cooperatively with p80cdc25 to dephosphorylate Tyr15 of p34cdc2. Images PMID:1464318

Millar, J B; Lenaers, G; Russell, P



The spindle protein CHICA mediates localization of the chromokinesin Kid to the mitotic spindle.  


Microtubule-based motor proteins provide essential forces for bipolar organization of spindle microtubules and chromosome movement, prerequisites of chromosome segregation during the cell cycle. Here, we describe the functional characterization of a novel spindle protein, termed "CHICA," that was originally identified in a proteomic survey of the human spindle apparatus [1]. We show that CHICA localizes to the mitotic spindle and is both upregulated and phosphorylated during mitosis. CHICA-depleted cells form shorter spindles and fail to organize a proper metaphase plate, highly reminiscent of the phenotype observed upon depletion of the chromokinesin Kid, a key mediator of polar ejection forces [2-6]. We further show that CHICA coimmunoprecipitates with Kid and is required for the spindle localization of Kid without affecting its chromosome association. Moreover, upon depletion of either CHICA or Kid (or both proteins simultaneously), chromosomes collapse onto the poles of monastrol-induced monopolar spindles. We conclude that CHICA represents a novel interaction partner of the chromokinesin Kid that is required for the generation of polar ejection forces and chromosome congression. PMID:18485706

Santamaria, Anna; Nagel, Susanna; Sillje, Herman H W; Nigg, Erich A



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



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



Rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol using controlled microwave-assisted synthesis.  


We present here a protocol for the synthesis of the dihydropyrimidine (DHPM) derivative monastrol, which is known to be a specific mitotic kinesin Eg5 inhibitor. By applying controlled microwave heating under sealed-vessel conditions, the synthesis via the one-pot three-component Biginelli condensation can be performed in a shorter reaction time (30 min) compared with conventional heating methods that normally require several hours of reflux heating. For the purification of the crude target compound, two different methods are presented. The first protocol includes a simple precipitation/filtration step to provide monastrol in 76% isolated yield and high purity so that no recrystallization step is necessary. This can be ascribed to the microwave heating technology in which less side-product formation is typically one of the advantages. In an alternative purification step, column chromatography is performed, which provides the product in a slightly higher yield (86%). Monastrol synthesis can be conducted in approximately 2 h by employing the precipitation/filtration purification method. PMID:17406591

Dallinger, Doris; Kappe, C Oliver



Crm1 is a mitotic effector of Ran-GTP in somatic cells.  


The Ran GTPase controls multiple cellular processes, including nuclear transport, mitotic checkpoints, spindle assembly and post-mitotic nuclear envelope reassembly. Here we examine the mitotic function of Crm1, the Ran-GTP-binding nuclear export receptor for leucine-rich cargo (bearing nuclear export sequence) and Snurportin-1 (ref. 3). We find that Crm1 localizes to kinetochores, and that Crm1 ternary complex assembly is essential for Ran-GTP-dependent recruitment of Ran GTPase-activating protein 1 (Ran-GAP1) and Ran-binding protein 2 (Ran-BP2) to kinetochores. We further show that Crm1 inhibition by leptomycin B disrupts mitotic progression and chromosome segregation. Analysis of spindles within leptomycin B-treated cells shows that their centromeres were under increased tension. In leptomycin B-treated cells, centromeres frequently associated with continuous microtubule bundles that spanned the centromeres, indicating that their kinetochores do not maintain discrete end-on attachments to single kinetochore fibres. Similar spindle defects were observed in temperature-sensitive Ran pathway mutants (tsBN2 cells). Taken together, our findings demonstrate that Crm1 and Ran-GTP are essential for Ran-BP2/Ran-GAP1 recruitment to kinetochores, for definition of kinetochore fibres and for chromosome segregation at anaphase. Thus, Crm1 is a critical Ran-GTP effector for mitotic spindle assembly and function in somatic cells. PMID:15908946

Arnaoutov, Alexei; Azuma, Yoshiaki; Ribbeck, Katharina; Joseph, Jomon; Boyarchuk, Yekaterina; Karpova, Tatiana; McNally, James; Dasso, Mary



Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation.  


Histone H3 (H3) phosphorylation at Ser(10) occurs during mitosis in eukaryotes and was recently shown to play an important role in chromosome condensation in Tetrahymena. When producing monoclonal antibodies that recognize glial fibrillary acidic protein phosphorylation at Thr(7), we obtained some monoclonal antibodies that cross-reacted with early mitotic chromosomes. They reacted with 15-kDa phosphoprotein specifically in mitotic cell lysate. With microsequencing, this phosphoprotein was proved to be H3. Mutational analysis revealed that they recognized H3 Ser(28) phosphorylation. Then we produced a monoclonal antibody, HTA28, using a phosphopeptide corresponding to phosphorylated H3 Ser(28). This antibody specifically recognized the phosphorylation of H3 Ser(28) but not that of glial fibrillary acidic protein Thr(7). Immunocytochemical studies with HTA28 revealed that Ser(28) phosphorylation occurred in chromosomes predominantly during early mitosis and coincided with the initiation of mitotic chromosome condensation. Biochemical analyses using (32)P-labeled mitotic cells also confirmed that H3 is phosphorylated at Ser(28) during early mitosis. In addition, we found that H3 is phosphorylated at Ser(28) as well as Ser(10) when premature chromosome condensation was induced in tsBN2 cells. These observations suggest that H3 phosphorylation at Ser(28), together with Ser(10), is a conserved event and is likely to be involved in mitotic chromosome condensation. PMID:10464286

Goto, H; Tomono, Y; Ajiro, K; Kosako, H; Fujita, M; Sakurai, M; Okawa, K; Iwamatsu, A; Okigaki, T; Takahashi, T; Inagaki, M



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; Lüders, Jens



Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation  

PubMed Central

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



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

PubMed Central

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

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



Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21(Cip1).  


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 G(1)/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 p21 (Cip1). Lack of Aurora B does not prevent mitotic entry but results in a premature exit from prometaphase in the presence of increased p21(Cip1)-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 p21(Cip1) rescues Cdk1 activity and prevents premature mitotic exit in Aurora B-deficient cells. These results suggest that Aurora B represses p21(Cip1), preventing delayed DNA replication, Cdk inhibition and premature mitotic exit. The upregulation of p21(Cip1) 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



High sensitivity optical fiber temperature sensor based on the temperature cross-sensitivity feature of RI-sensitive device  

NASA Astrophysics Data System (ADS)

Considerable part of optical fiber refractive index (RI) sensors suffer from the drawback of cross-sensitivity to temperature because of the thermo-optic effect of materials. In this paper, we propose a straightforward method to utilize the temperature cross-sensitivity feature of an optical fiber RI-sensitive device and thus got a high sensitivity temperature sensor. The sensor consists of a single mode fiber-multimode fiber core(MMFC)-single mode fiber structural refractometer encapsulated into a deionized water-filled cylindrical aluminum alloy shell. Benefiting from the larger thermo-optic coefficient difference between water and MMFC compared with the general cladding and core, the wavelength of transmitted spectrum presents enhanced shift when the ambient temperature change and thus get a higher temperature sensitivity. Experimental results show that the enhanced temperature sensitivity is about 358 pm/°C, which is almost 30 times that of the inherent temperature sensitivity.

Sun, Hao; Hu, Manli; Rong, Qiangzhou; Du, Yanying; Yang, Hangzhou; Qiao, Xueguang



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. PMID:25426412

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



Optimal design of high damping force engine mount featuring MR valve structure with both annular and radial flow paths  

NASA Astrophysics Data System (ADS)

This paper focuses on the optimal design of a compact and high damping force engine mount featuring magnetorheological fluid (MRF). In the mount, a MR valve structure with both annular and radial flows is employed to generate a high damping force. First, the configuration and working principle of the proposed MR mount is introduced. The MRF flows in the mount are then analyzed and the governing equations of the MR mount are derived based on the Bingham plastic behavior of the MRF. An optimal design of the MR mount is then performed to find the optimal structure of the MR valve to generate a maximum damping force with certain design constraints. In addition, the gap size of MRF ducts is empirically chosen considering the ‘lockup’ problem of the mount at high frequency. Performance of the optimized MR mount is then evaluated based on finite element analysis and discussions on performance results of the optimized MR mount are given. The effectiveness of the proposed MR engine mount is demonstrated via computer simulation by presenting damping force and power consumption.

Nguyen, Q. H.; Choi, S. B.; Lee, Y. S.; Han, M. S.



Biological features of core networks that result from a high-fat diet in hepatic and pulmonary tissues in mammary tumour-bearing, obesity-resistant mice.  


We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells. PMID:23234678

Kim, Eun Ji; Oh, Hea Young; Heo, Hyoung-Sam; Hong, Ji Eun; Jung, Sung-Jae; Lee, Ki Won; Park, Jong Hoon; Hur, Cheol-Goo; Park, Jung Han Yoon



Condensed mitotic chromosome structure at nanometer resolution using PALM and EGFP- histones.  


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

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



High resolution PFPE-based molding High resolution PFPE-based molding High resolution PFPE-based molding techniques for nanofabrication of high pattern density sub-20 nm features: A fundamental materials approach  

SciTech Connect

ABSTRACT. Described herein is the development and investigation of PFPE-based elastomers for high resolution replica molding applications. The modulus of the elastomeric materials was increased through synthetic and additive approaches while maintaining relatively low surface energies (<25 mN/m). Using practically relevant large area master templates, we show that the resolution of the molds is strongly dependant upon the elastomeric mold modulus. A composite mold approach was used to form flexible molds out of stiff, high modulus materials that allow for replication of sub-20 nm post structures. Sub-100 nm line grating master templates, formed using e-beam lithography, were used to determine the experimental stability of the molding materials. It was observed that as the feature spacing decreased, high modulus composite molds were able to effectively replicate the nano-grating structures without cracking or tear-out defects that typically occur with high modulus elastomers.

Williams, Stuart S [University of North Carolina, Chapel Hill; Samulski, Edward [University of North Carolina, Chapel Hill; Lopez, Renee [University of North Carolina, Chapel Hill; Ruiz, Ricardo [Hitachi; DeSimone, Joseph [University of North Carolina, Chapel Hill; Retterer, Scott T [ORNL



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


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



The desire to achieve both high power density and high power conversion efficiency leads to several required features of a first wall and blanket concept. Achieving high  

E-print Network

, resulting in low structural distortion and thermal stresses. 5. The lithium flow rate is approximatelyThe desire to achieve both high power density and high power conversion efficiency leads to several properties (high thermal conductivity, low thermal expansion, etc.). Achieving high power conversion

California at Los Angeles, University of


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.



Drosophila Xpd Regulates Cdk7 Localization, Mitotic Kinase Activity, Spindle Dynamics, and Chromosome Segregation  

PubMed Central

The trimeric CAK complex functions in cell cycle control by phosphorylating and activating Cdks while TFIIH-linked CAK functions in transcription. CAK also associates into a tetramer with Xpd, and our analysis of young Drosophila embryos that do not require transcription now suggests a cell cycle function for this interaction. xpd is essential for the coordination and rapid progression of the mitotic divisions during the late nuclear division cycles. Lack of Xpd also causes defects in the dynamics of the mitotic spindle and chromosomal instability as seen in the failure to segregate chromosomes properly during ana- and telophase. These defects appear to be also nucleotide excision repair (NER)–independent. In the absence of Xpd, misrouted spindle microtubules attach to chromosomes of neighboring mitotic figures, removing them from their normal location and causing multipolar spindles and aneuploidy. Lack of Xpd also causes changes in the dynamics of subcellular and temporal distribution of the CAK component Cdk7 and local mitotic kinase activity. xpd thus functions normally to re-localize Cdk7(CAK) to different subcellular compartments, apparently removing it from its cell cycle substrate, the mitotic Cdk. This work proves that the multitask protein Xpd also plays an essential role in cell cycle regulation that appears to be independent of transcription or NER. Xpd dynamically localizes Cdk7/CAK to and away from subcellular substrates, thereby controlling local mitotic kinase activity. Possibly through this activity, xpd controls spindle dynamics and chromosome segregation in our model system. This novel role of xpd should also lead to new insights into the understanding of the neurological and cancer aspects of the human XPD disease phenotypes. PMID:20300654

Suter, Beat



High-risk histomorphological features in retinoblastoma and their association with p53 expression: An Indian experience  

PubMed Central

Introduction: Histopathological features in retinoblastoma are considered high-risk factors (HRF) for tumor progression and metastasis, thus their presence becomes an indication for adjuvant chemotherapy. Present study was undertaken to evaluate the incidence of HRF in retinoblastoma and to correlate them with p53 expression. Materials and Methods: This was a retrospective study where 17 diagnosed cases of retinoblastoma were included. Cases were re-evaluated for various histomorphological parameters. Immuno-histochemical analysis was done with p53 antibody by Streptavidin biotin method. Results: The patients were in the age range of 1.5-50 years. Common histological features included necrosis (70.5%), calcification (64.7%), and retinal detachment (58.8%). Incidence of various morphological parameters was anterior chamber seeding (47.2%), ciliary body involvement (29.4%), iris involvement (29.4%), choroid involvement (58.8%), scleral invasion (29.4%), extrascleral invasion (11.8%), and optic nerve infiltration (23.5%). p53 expression was present in four cases out of 13 cases (30.7%) and showed a significant association with choroid invasion (P = 0.02). Discussion: The presence of HRF should alert the physician for a possible metastasis, and such patients should be kept on regular follow-up to detect an early recurrence. p53 expression, a known poor prognostic indicator, showed significant association with choroid invasion, however, no association was seen with other HRF. Conclusion: Histopathological HRF have significant therapeutic and prognostic implications. The incidence of HRF is higher in developing countries as patients present with a more advanced stage of disease. p53 expression is significantly associated with choroid invasion out of all HRF. PMID:25494248

Rao, Seema; Sobti, Parul; Khurana, Nita; Kamlesh



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.



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

PubMed Central

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

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



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

E-print Network

132 ? PPase AS 1 - - 3 + - 4 + + Nocodazole treated cells 2 - - *Page 3 of 15 (page number not for citation purposes) mechanisms governing mitotic-dependent proteasomal degradation of Myf5 are conserved in Xenopus egg extracts. hyperphosphorylation... phosphatase (? PPase), as indicated. Samples were resolved by 10% SDS-PAGE and analyzed using a Phos- phoImager. (D) A mitotic extract was first incubated with 200 µM MG132, or the same volume of pure DMSO as a control, for 10 min at 25°C; dephosphorylated...

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



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

SciTech Connect

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

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



Induced rates of mitotic crossing over and possible mitotic gene conversion per wing anlage cell in Drosophila melanogaster by X rays and fission neutrons  

Microsoft Academic Search

As a model for chromosome aberrations, radiation-induced mitotic recombination of mwh and flr genes in Drosophila melanogaster strain (mwh +\\/+ flr) was quantitatively studied. Fission neutrons were five to six times more effective than X rays per unit dose in producing either crossover-mwh\\/flr twins and mwh singles-or flr singles, indicating that common processes are involved in the production of crossover

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



Low Rates of Adjuvant Radiation in Patients With Nonmetastatic Prostate Cancer With High-Risk Pathologic Features  

PubMed Central

BACKGROUND The 2013 American Urological Association/American Society for Radiation Oncology consensus guidelines recommend offering adjuvant radiotherapy (RT) after radical prostatectomy in patients with high-risk pathologic features for recurrence. In the current study, the authors examined practice patterns of adjuvant RT use in patients with elevated pathologic risk factors over a time period spanning the publication of supporting randomized evidence. METHODS Using the National Cancer Data Base, a total of 130,681 patients were identified who underwent surgical resection for prostate cancer between 2004 and 2011 with at least 1 of the following pathologic risk factors for early biochemical failure: pT3a disease or higher, positive surgical margins and/or lymph node-positive disease. Using multivariable logistic regression, the authors examined factors associated with adjuvant RT use including patient, clinical, demographic, and temporal characteristics. RESULTS Adjuvant RT was administered to 9.9% of the patients with at least 1 pathologic risk factor. Use of adjuvant RT did not change over the study period (P = .23). On multivariable analysis, we found that patients treated at high-volume surgical facilities were less likely to receive adjuvant RT (15.9% vs 7.8%; odds ratio, 0.58 [95% confidence interval, 0.50–0.65]; P<.0001). Older age, comorbidities, black race, lower income, and lower population density were also associated with lower rates of adjuvant RT. CONCLUSIONS Use of adjuvant RT is uncommon and remained unchanged between 2004 and 2011. Patients treated at high-volume surgical facilities are less likely to receive adjuvant RT, irrespective of margin status. PMID:24917426

Kalbasi, Anusha; Swisher-McClure, Samuel; Mitra, Nandita; Sunderland, Robert; Smaldone, Marc C.; Uzzo, Robert G.; Bekelman, Justin E.



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.  


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



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



Multi-kinase inhibitor C1 triggers mitotic catastrophe of glioma stem cells mainly through MELK kinase inhibition.  


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

Minata, Mutsuko; Gu, Chunyu; Joshi, Kaushal; Nakano-Okuno, Mariko; Hong, Christopher; Nguyen, Chi-Hung; Kornblum, Harley I; Molla, Annie; Nakano, Ichiro



Jab1/CSN5 mediates E2F dependent expression of mitotic and apoptotic but not DNA replication targets.  


The E2F transcription factors are critical regulators of cell cycle and cell fate control. Several classes of E2F target genes have been categorized based on their roles in DNA replication, mitosis, apoptosis, DNA repair, etc. How E2Fs coordinate the appropriate and timely expression of these functionally disparate gene products is poorly understood at a molecular level. We previously showed that the E2F1 binding partner Jab1/CSN5 promotes E2F1-dependent induction of apoptosis but not proliferation. To better understand how Jab1 regulates E2F1 dependent transcription, we performed gene expression analysis to identify E2F target genes most and least affected by shRNA depletion of Jab1. We find that a significant number of apoptotic and mitotic E2F target genes are poorly expressed in cells lacking Jab1/CSN5, whereas DNA replication genes are generally still highly expressed. Chromatin immunoprecipitation analysis indicates that both Jab1 and E2F1 co-occupy apoptotic and mitotic, but not DNA replication target genes. We explored a potential connection between PI3K activity and Jab1/E2F1 target gene induction, and found that E2F1/Jab1 co-induction of apoptotic target genes can be inhibited by activated PI3K. Furthermore, PI3K activity interferes with formation of the E2F1/Jab1 complex by co-immunoprecipitation. Jab1/CSN5 is upregulated in a variety of human tumors, but it's unclear how its pro-proliferatory and apoptotic functions are regulated in this context. We explored the link between increased Jab1 levels and PI3K function in tumors and detected a highly significant correlation between elevated Jab1/CSN5 levels and PI3K activity in breast, ovarian, lung and prostate cancers. PMID:21937878

Lu, Huarui; Liang, Xudong; Issaenko, Olga A; Hallstrom, Timothy C



Cytologic features of epithelioid hemangioendothelioma.  


To determine cytologic features of epithelioid hemangioendothelioma (EHE) that would enable accurate diagnosis, we evaluated fine-needle aspiration biopsy (FNAB) smears from 11 histologically confirmed EHEs. The variably cellular smears comprised dispersed single cells and occasional cell aggregates. Dense stromal fragments were present in association with some tissue fragments. The cells were epithelioid, containing moderate or large amounts of dense cytoplasm. Nuclei exhibited mild pleomorphism, and nuclear grooves were identified in all cases. At least occasional intranuclear pseudoinclusions (INPIs) and intracytoplasmic lumina (ICLs) were present in all cases and in 9 cases (82%), respectively, and rare erythrocytes were seen within ICLs in 5 cases (45%). Mitotic figures were identified in 4 cases (36%). The background was bloody in 6 cases (55%) and contained hemosiderin and/or hemosiderin-laden macrophages in 5 cases (45%). The combination of the following features in FNAB samples should raise strong suspicion for EHE: predominantly dispersed single cells with occasional cohesive cell clusters; epithelioid cytomorphology; dense cytoplasm with well-defined cytoplasmic borders; ICLs (with or without erythrocytes), INPIs, and nuclear grooves. The presence of these features should prompt correlation with clinical, radiologic, and histologic features and immunohistochemical evaluation using vascular markers. PMID:22031312

Murali, Rajmohan; Zarka, Matthew A; Ocal, Idris T; Tazelaar, Henry D



Morphological Features of Cell Blocks Prepared from Residual Liqui-PREP Samples Can Distinguish between High-Grade Squamous Intraepithelial Lesions and Squamous Cell Carcinomas  

Microsoft Academic Search

Objective: To evaluate the diagnostic value and compare morphological features of cell block sections of high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinomas (SCC). Study Design: A total of 135 cell blocks were prepared from residual Liqui-PREP samples. Of these, 43 biopsy-confirmed cases (24 HSIL and 19 SCC) were reviewed. Morphological features determined included cell clusters, epithelial-stromal interface, stromal

Qingzhu Wei; Jianghuan Liu; Zhixiong Zhang; Qiao Yang; Tong Zhao



Whole-body magnetic resonance imaging featuring moving table continuous data acquisition with high-precision position feedback.  


A novel setup for whole-body MR imaging with moving table continuous data acquisition has been developed and evaluated. The setup features a manually positioned moving table platform with integrated phased-array surface radiofrequency coils. A high-precision laser position sensor was integrated into the system to provide real-time positional data that were used to compensate for nonlinear manual table translation. This setup enables continuous 2D and 3D whole-body data acquisition during table movement with surface coil image quality. The concept has been successfully evaluated with whole-body steady-state free precession (TrueFISP) anatomic imaging in five healthy volunteers. Seamless coronal and sagittal slices of continually acquired whole-body data during table movement were accurately reconstructed. The proposed strategy is potentially useful for a variety of applications, including whole-body metastasis screening, whole-body MR angiography, large field-of-view imaging in short bore systems, and for moving table applications during MR-guided interventions. PMID:16086302

Zenge, Michael O; Ladd, Mark E; Vogt, Florian M; Brauck, Katja; Barkhausen, Joerg; Quick, Harald H



A highly selective and sensitive fluorescent probe for quantitative detection of Hg(2+) based on aggregation-induced emission features.  


A ?-conjugated cyanostilbene derivative of (Z)-2-(4-nitrophenyl)-3-(4-(vinyloxy)phenyl)acrylonitrile (CN-vinyl) had been designed, synthesized and confirmed by the standard spectroscopic analyses. CN-vinyl possesses an unusual high emissive aggregation-induced emission (AIE) feature in a tetrahydrofuran/water mixture (2:8, v/v). The fluorescence intensity of CN-vinyl can be quenched linearly with the addition of Hg(2+) in a range of 0-50?M with a correlation coefficient of R(2)=0.9957. The detection limit of Hg(2+) is 37nM. The mechanism for Hg(2+)-mediated optical properties of CN-vinyl is due to the selective cleavage of vinyl group by Hg(2+). Accuracy of the proposed methodology was evaluated by means of the recovery study in real samples and the analyzing certified reference material of the standard solution of Hg(2+). By this novel strategy, CN-vinyl can be used for quantitative detection of Hg(2+) as well as the presence of other physiological relevant metal ions. PMID:25476389

Wang, Aizhi; Yang, Yunxu; Yu, Feifei; Xue, Lingwei; Hu, Biwei; Fan, Weiping; Dong, Yajun



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


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



Conventional and high resolution scanning electron microscopy of outer and inner surface features of cerebellar nerve cells.  


This paper provides an exploration into the inner and outer surfaces of vertebrate cerebellar neurons utilizing secondary electron (SE-I and SE-II) topographic contrasts. SE-I enriched chromium coated, cryofractured Rhesus monkey cerebellum staged within the condenser/objective stage of SEMs equipped with high brightness LaB6 and field emission emitters generated quality images of intact and fractured nerve cells studied at intermediate and high magnifications. These images were compared with conventional SE-III images of gold-palladium teleost fish cerebellar neurons and transmission electron micrographs of mouse cerebellar nerve cells obtained either by thin-sections or freeze-etch replicas. Chromium coated Rhesus monkey granule and Golgi cell surfaces revealed smooth, accurately delineated profiles of true cell surface features, which lacked the SE-III dominated brilliance of conventional teleost fish gold or gold-palladium, decorated neurons. Chromium coated fractured nerve processes showed the outer smooth surface of interconnected anastomotic networks or ER tubules, vesicles and cisterns. Cross fractured presynaptic endings of parallel fibers in the molecular layer exhibited spheroidal synaptic vesicles and SE-I edge brightness contrast delineated their limiting plasma membranes. Fractured synaptic endings showed a homogeneous extravesicular material surrounding the synaptic vesicles. The presynaptic dense projections appeared as columnar shaped structures. The postsynaptic membrane and associated postsynaptic density showed a discontinuous surface formed by round subunits 25-35 nm in diameter. The neuroglial cytoplasm ensheathing nerve process exhibited a smooth discontinuous surface. The surface of the myelin sheath showed a mixed population of globular structures 10-30 nm in diameter, apparently corresponding, according to freeze-etch images, to protein and phospholipid microdomains. PMID:1458441

Castejón, O J; Apkarian, R P



VLSI processor with a configurable processing element array for balanced feature extraction in high-resolution images  

NASA Astrophysics Data System (ADS)

A VLSI processor employing a configurable processing element array (PEA) is developed for a newly proposed balanced feature extraction algorithm. In the algorithm, the input image is divided into square regions and the number of features is determined by noise effect analysis in each region. Regions of different sizes are used according to the resolutions and contents of input images. Therefore, inside the PEA, processing elements are hierarchically grouped for feature extraction in regions of different sizes. A proof-of-concept chip is fabricated using a 0.18 µm CMOS technology with a 32 × 32 PEA. From measurement results, a speed of 7.5 kfps is achieved for feature extraction in 128 × 128 pixel regions when operating the chip at 45 MHz, and a speed of 55 fps is also achieved for feature extraction in 1920 × 1080 pixel images.

Zhu, Hongbo; Shibata, Tadashi



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.



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

Microsoft Academic Search

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

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



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.


RanGTP and CLASP1 cooperate to position the mitotic spindle  

PubMed Central

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



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



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



Microsoft Academic Search

The mitotic figures in dividing cells of sea urchin embryos, from first division to the onset of cilia formation, were studied with regard to the filament system and its relation to kinetochores, chromosomes, and poles, as well as to fixation conditions which would best preserve these structures. With regard to fixation, variations in the salt concentration and pH of the




Separation of Linked Markers in Chinese Hamster Cell Hybrids: Mitotic Recombination Is Not Involved  

PubMed Central

A search for mitotic recombination was carried out using mutant subclones of cultured Chinese hamster ovary cells. Recombination events were sought between the linked loci specifying the enzymes hypoxanthine phosphoribosyl transferase and glucose-6-phosphate dehydrogenase. It was shown by fluctuation analysis that markers at these two loci co-segregate from doubly heterozygous pseudotetraploid hybrid cells more than 90% of the time. The minority class of segregants, which had lost one marker without losing the other, were genetically analyzed to distinguish between the possibilities of mitotic recombination and deletion of chromosomal material. Nine clones in which a linkage disruption had occured were studied, using further cell hybridization and segregation. In three cases, a recessive lethal loss of genetic information was indicated, suggesting the deletion mechanism. In six cases, it was demonstrated that no new linkage relationships had been established concomitant with linkage disruption. Thus, in all nine clones, the evidence indicated that mitotic recombination was not involved in the events that disrupted linkage between these two loci. If mitotic recombination takes place at all in this system, the rate must be less than about 10-6 per cell per generation. PMID:744475

Rosenstraus, Maurice J.; Chasin, Lawrence A.



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

SciTech Connect

Highlights: •NuMA is modified by SUMO-1 in a cell cycle-dependent manner. •NuMA lysine 1766 is the primary target site for SUMOylation. •SUMOylation-deficient NuMA induces multiple spindle poles during mitosis. •SUMOylated NuMA induces microtubule bundling. -- Abstract: 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.

Seo, Jae Sung; Kim, Ha Na; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Ki Sa [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)] [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Yoon, Hyun-Joo [TissueGene Inc. 9605 Medical Center Dr., Rockville, MD 20850 (United States)] [TissueGene Inc. 9605 Medical Center Dr., Rockville, MD 20850 (United States); Yoo, Hae Yong [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of)] [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of); Choi, Cheol Yong, E-mail: [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)



Functional Characterisation and Drug Target Validation of a Mitotic Kinesin13 in Trypanosoma brucei  

Microsoft Academic Search

Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have

Kuan Yoow Chan; Keith R. Matthews; Klaus Ersfeld



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


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



Saccharomyces cerevisiae Duo1p and Dam1p, Novel Proteins Involved in Mitotic Spindle Function  

PubMed Central

In this paper, we describe the identification and characterization of two novel and essential mitotic spindle proteins, Duo1p and Dam1p. Duo1p was isolated because its overexpression caused defects in mitosis and a mitotic arrest. Duo1p was localized by immunofluorescence, by immunoelectron microscopy, and by tagging with green fluorescent protein (GFP), to intranuclear spindle microtubules and spindle pole bodies. Temperature-sensitive duo1 mutants arrest with short spindles. This arrest is dependent on the mitotic checkpoint. Dam1p was identified by two-hybrid analysis as a protein that binds to Duo1p. By expressing a GFP–Dam1p fusion protein in yeast, Dam1p was also shown to be associated with intranuclear spindle microtubules and spindle pole bodies in vivo. As with Duo1p, overproduction of Dam1p caused mitotic defects. Biochemical experiments demonstrated that Dam1p binds directly to microtubules with micromolar affinity. We suggest that Dam1p might localize Duo1p to intranuclear microtubules and spindle pole bodies to provide a previously unrecognized function (or functions) required for mitosis. PMID:9817759

Hofmann, Christian; Cheeseman, Iain M.; Goode, Bruce L.; McDonald, Kent L.; Barnes, Georjana; Drubin, David G.



WT1 interacts with MAD2 and regulates mitotic checkpoint function.  


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



Formation in vitro of Sperm Pronuclei and Mitotic Chromosomes Induced by Amphibian Ooplasmic Components  

Microsoft Academic Search

A cell-free preparation of the cytoplasm from activated eggs of Rana pipiens induces, in demembranated sperm nuclei of Xenopus laevis, formation of a nuclear envelope, chromatin decondensation, initiation of DNA synthesis, and chromosome condensation. Both soluble and particulate cytoplasmic constituents are required to initiate these processes in vitro. The observed changes resemble processes occurring during fertilization and the mitotic cycle

Manfred J. Lohka; Yoshio Masui



Diurnal changes in mitotic activity and DNA synthesis in normal and tumor tissues of rats  

Microsoft Academic Search

Diurnal changes in mitotic activity and in the number of cells synthesizing DNA in a spontaneous sarcoma of rats and in the esophageal and corneal epithelium were studied in noninbred albino rats weighing 190 g by autoradiography. The animals were killed in groups every 3 h for 24 h, 1 h after receiving an injection of thymidine-H 3. The experiments

L. V. Sokolova; A. G. Mustafin; V. N. Dobrokhotov; S. I. Baluev



Pds1 and Esp1 control both anaphase and mitotic exit in normal cells  

E-print Network

Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage Rachel L exit. Pds1 blocks cyclin destruction by inhibiting its binding partner Esp1. Mutations in ESP1 delay cyclin destruction; overexpression of ESP1 causes premature cyclin destruction in cells arrested

Morgan, David



Microsoft Academic Search

The mitotic cell-cycle mutation cdc4 has been reported to block the initia- tion of nuclear DNA replication and the separation of spindle plaques after their replication. Meiosis in cdc4\\/cdc4 diploids is normal at the permissive tem- perature (25\\



Regulation of Mitotic Cytoskeleton Dynamics and Cytokinesis by Integrin-Linked Kinase in Retinoblastoma Cells  

PubMed Central

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

Sharma, Manju; Assi, Kiran; Salh, Baljinder; Cox, Michael E.; Mills, Julia



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

E-print Network

Karyotype 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 counts and construction of karyotypes on the basis of Feulgen staining. Since the chromosomes of Bromus

Gill, Kulvinder


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

SciTech Connect

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

Smith, P.F.



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


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



Fluorescent antibody localization of myosin in the cytoplasm, cleavage furrow, and mitotic spindle of human cells  

PubMed Central

We have studied the distribution of myosin molecules in human cells using myosin-specific antibody coupled with fluorescent dyes. Rabbits were immunized with platelet myosin or myosin rod. They produced antisera which precipitated only myosin among all the components in crude platelet extracts. From these antisera we isolated immunoglobulin- G (IgG) and conjugated it with tetramethylrhodamine or fluorescein. We separated IgG with 2-5 fluorochromes per molecule from both under- and over-conjugated IgG by ion exchange chromatography and used it to stain acetone-treated cells. The following controls established the specificity of the staining patterns: (a) staining with labeled preimmune IgG; (b) staining with labeled immune IgG adsorbed with purified myosin; (c) staining with labeled immune IgG mixed with either unlabeled preimmune or immune serum; and (d) staining with labeled antibody purified by affinity chromatography. In blood smears, only the cytoplasm of platelets and leukocytes stained. In spread Enson and HeLa cells, stress fibers stained strongly in closely spaced 0.5 mum spots. The cytoplasm stained uniformly in those cells presumed to be motile before acetone treatment. In dividing HeLa cells there was a high concentration of myosin-specific staining in the vicinity of the contractole ring and in the mitotic spindle, especially the region between the chromosomes and the poles. We detected no staining of erythrocytes, or nuclei of leukocytes and cultured cells, or the surface of platelets and cultured cells. PMID:62755



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)



The very high rotators in the late-B and early-A stars: Shell stars with Si IV and C IV features the case of HD 119921  

NASA Technical Reports Server (NTRS)

Study of several stars in the late B and early A spectral types shows that very high rotators are associated with shell characteristics (sometimes not detected at all in the visible spectra) and also with C IV and some Si IV spectral absorption features which can be explained by circumstellar phenomena superimposed over stellar metallic blends. These particularities are evidenced by comparison with other spectra of low and high rotators in the same spectral range. HD 119921, a star with similar characteristics to the other ones of the sample, is given special attention. A possible scenario is suggested to explain the observed superionization features.

Freireferrero, R.; Bruhweiler, Frederick C.; Grady, C. A.



High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): cytogenetic features, clinical characteristics and outcome.  


High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and -negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95% CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain. PMID:24352198

Chilton, L; Buck, G; Harrison, C J; Ketterling, R P; Rowe, J M; Tallman, M S; Goldstone, A H; Fielding, A K; Moorman, A V



Mlp1 Acts as a Mitotic Scaffold to Spatially Regulate Spindle Assembly Checkpoint Proteins in Aspergillus nidulans  

PubMed Central

During open mitosis several nuclear pore complex (NPC) proteins have mitotic specific localizations and functions. We find that the Aspergillus nidulans Mlp1 NPC protein has previously unrealized mitotic roles involving spatial regulation of spindle assembly checkpoint (SAC) proteins. In interphase, An-Mlp1 tethers the An-Mad1 and An-Mad2 SAC proteins to NPCs. During a normal mitosis, An-Mlp1, An-Mad1, and An-Mad2 localize similarly on, and around, kinetochores until telophase when they transiently localize near the spindle but not at kinetochores. During SAC activation, An-Mlp1 remains associated with kinetochores in a manner similar to An-Mad1 and An-Mad2. Although An-Mlp1 is not required for An-Mad1 kinetochore localization during early mitosis, it is essential to maintain An-Mad1 in the extended region around kinetochores in early mitosis and near the spindle in telophase. Our data are consistent with An-Mlp1 being part of a mitotic spindle matrix similar to its Drosophila orthologue and demonstrate that this matrix localizes SAC proteins. By maintaining SAC proteins near the mitotic apparatus, An-Mlp1 may help monitor mitotic progression and coordinate efficient mitotic exit. Consistent with this possibility, An-Mad1 and An-Mlp1 redistribute from the telophase matrix and associate with segregated kinetochores when mitotic exit is prevented by expression of nondegradable cyclin B. PMID:19225157

De Souza, Colin P.; Hashmi, Shahr B.; Nayak, Tania; Oakley, Berl



Bayesian analysis of X-ray jet features of the high redshift quasar jets observed with Chandra  

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. Results from Chandra X-ray and multi-frequency VLA imaging observations of a sample of 11 high- redshift (z > 2) quasars with kilo-parsec scale radio jets are reported. The sample consists of a set of four z ? 3.6 flat-spectrum radio quasars, and seven intermediate redshift (z = 2.1 - 2.9) quasars comprised of four sources with integrated steep radio spectra and three with flat radio spectra.We implement a Bayesian image analysis program, Low-count Image Reconstruction and Analysis (LIRA) , to analyze jet features in the X-ray images of the high redshift quasars. Out of the 36 regions where knots are visible in the radio jets, nine showed detectable X-ray emission. Significant detections are based on the upper bound p-value test based on LIRA simulations. The X-ray and radio properties of this sample combined are examined and compared to lower-redshift samples.This work is supported in part by the National Science Foundation REU and the Department of Defense ASSURE programs under NSF Grant no.1262851 and by the Smithsonian Institution, and by NASA Contract NAS8-39073 to the Chandra X-ray Center (CXC). This research has made use of data obtained from the Chandra Data Archive and Chandra Source Catalog, and software provided by the CXC in the application packages CIAO, ChIPS, and Sherpa. Work is also supported by the Chandra grant GO4-15099X.

McKeough, Kathryn; Siemiginowska, Aneta; Kashyap, Vinay; Stein, Nathan; Cheung, Chi C.



Targeting Alp7/TACC to the spindle pole body is essential for mitotic spindle assembly in fission yeast  

PubMed Central

The conserved TACC protein family localises to the centrosome (the spindle pole body, SPB in fungi) and mitotic spindles, thereby playing a crucial role in bipolar spindle assembly. However, it remains elusive how TACC proteins are recruited to the centrosome/SPB. Here, using fission yeast Alp7/TACC, we have determined clustered five amino acid residues within the TACC domain required for SPB localisation. Critically, these sequences are essential for the functions of Alp7, including proper spindle formation and mitotic progression. Moreover, we have identified pericentrin-like Pcp1 as a loading factor to the mitotic SPB, although Pcp1 is not a sole platform. PMID:24937146

Tang, Ngang Heok; Okada, Naoyuki; Fong, Chii Shyang; Arai, Kunio; Sato, Masamitsu; Toda, Takashi



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


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. PMID:24971641

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



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

SciTech Connect

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

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



Loop L5 Assumes Three Distinct Orientations during the ATPase Cycle of the Mitotic Kinesin Eg5  

PubMed Central

Members of the kinesin superfamily of molecular motors differ in several key structural domains, which probably allows these molecular motors to serve the different physiologies required of them. One of the most variable of these is a stem-loop motif referred to as L5. This loop is longest in the mitotic kinesin Eg5, and previous structural studies have shown that it can assume different conformations in different nucleotide states. However, enzymatic domains often consist of a mixture of conformations whose distribution shifts in response to substrate binding or product release, and this information is not available from the “static” images that structural studies provide. We have addressed this issue in the case of Eg5 by attaching a fluorescent probe to L5 and examining its fluorescence, using both steady state and time-resolved methods. This reveals that L5 assumes an equilibrium mixture of three orientations that differ in their local environment and segmental mobility. Combining these studies with transient state kinetics demonstrates that there is a major shift in this distribution during transitions that interconvert weak and strong microtubule binding states. Finally, in conjunction with previous cryo-EM reconstructions of Eg5·microtubule complexes, these fluorescence studies suggest a model in which L5 regulates both nucleotide and microtubule binding through a set of reversible interactions with helix ?3. We propose that these features facilitate the production of sustained opposing force by Eg5, which underlies its role in supporting formation of a bipolar spindle in mitosis. PMID:24145034

Muretta, Joseph M.; Behnke-Parks, William M.; Major, Jennifer; Petersen, Karl J.; Goulet, Adeline; Moores, Carolyn A.; Thomas, David D.; Rosenfeld, Steven S.



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



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

straight-forward con- sideration of vehicle dynamics. 1 Introduction As developing autonomous off-roadPage 1 Abstract In the near future, off-road mobile robots will feature high levels of autonomy quite well for applications on paved sur- faces. Off-road conditions certainly make things more diffi

Kelly, Alonzo


Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer  

PubMed Central

Background To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors. Methods Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2. Results Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (? 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042). Conclusions Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer. PMID:20064215



High Prevalence of Polycystic Ovaries and Associated Clinical, Endocrine, and Metabolic Features in Women with Previous Gestational Diabetes Mellitus  

Microsoft Academic Search

The prevalence of polycystic ovaries, according to ultrasonography, and associated clinical, endocrine, and metabolic features were in- vestigated in women with previous gestational diabetes mellitus (GDM). Thirty-four women with GDM 3-5 yr before the investigation and 36 controls with uncomplicated pregnancies, selected for similar age, parity, and date of delivery, were investigated. The women with previous GDM showed a higher




Molecular bridging of mitotic RanGTP and aurora B kinase in the maintenance of kinetochore-microtubule attachments.  

E-print Network

??The multi-faceted RanGTPase has been implicated to be critically involved in nucleocytoplasmic transportation and cell cycle progression. However, the role of mitotic RanGTP in kinetochore-microtubule… (more)

Lee, Yoke Peng.



The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1.  

PubMed Central

The cis/trans peptidyl-prolyl isomerase, Pin1, is a regulator of mitosis that is well conserved from yeast to man. Here we demonstrate that depletion of Pin1-binding proteins from Xenopus egg extracts results in hyperphosphorylation and inactivation of the key mitotic regulator, Cdc2/cyclin B. We show biochemically that this phenotype is a consequence of Pin1 interaction with critical upstream regulators of Cdc2/cyclin B, including the Cdc2-directed phosphatase, Cdc25, and its known regulator, Plx1. Although Pin1 could interact with Plx1 during interphase and mitosis, only the phosphorylated, mitotically active form of Cdc25 was able to bind Pin1, an event we have recapitulated using in vitro phosphorylated Cdc25. Taken together, these data suggest that Pin1 may modulate cell cycle control through interaction with Cdc25 and its activator, Plx1. PMID:9482729

Crenshaw, D G; Yang, J; Means, A R; Kornbluth, S



Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2  

PubMed Central

The meiosis-specific synaptonemal complex protein SYCP3 has been reported to be aberrantly expressed in tumours. However, in contrast to its well-defined function in meiosis, its possible role in mitotic cells is entirely unknown. Here, we show that SYCP3 is expressed in a range of primary tumours and that it impairs chromosomal integrity in mitotic cells. Expression of SYCP3 inhibits the homologous recombination (HR) pathway mediated by RAD51, inducing hypersensitivity to DNA-damaging agents such as a poly(ADP-ribose) polymerase (PARP) inhibitor and chromosomal instability. SYCP3 forms a complex with BRCA2 and inhibits its role in HR. These findings highlight a new mechanism for chromosomal instability in cancer and extend the range of PARP-inhibitor sensitive tumours to those expressing SYCP3. PMID:22116401

Hosoya, Noriko; Okajima, Miyuki; Kinomura, Aiko; Fujii, Yoshihiro; Hiyama, Takashi; Sun, Jiying; Tashiro, Satoshi; Miyagawa, Kiyoshi



SON is a spliceosome-associated factor required for mitotic progression  

PubMed Central

The eukaryotic RNA splicing machinery is dedicated to the daunting task of excising intronic sequences on the many nascent RNA transcripts in a cell, and in doing so facilitates proper translation of its transcriptome. Notably, emerging evidence suggests that RNA splicing may also play direct roles in maintaining genome stability. Here we report the identification of the RNA/DNA-binding protein SON as a component of spliceosome that plays pleiotropic roles during mitotic progression. We found that SON is essential for cell proliferation, and that its inactivation triggers a MAD2-dependent mitotic delay. Moreover, SON deficiency is accompanied by defective chromosome congression, compromised chromosome segregation and cytokinesis, which in turn contributes to cellular aneuploidy and cell death. In summary, our study uncovers a specific link between SON and mitosis, and highlights the potential of RNA processing as additional regulatory mechanisms that govern cell proliferation and division. PMID:20581448

Sy, Shirley MH; Leung, Ka Man; Ching, Yick-Pang; Tipoe, George L; Man, Cornelia; Dong, Shuo



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

PubMed Central

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

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



Phospho-Ser383-Elk-1 is localized to the mitotic spindles during cell cycle and interacts with mitotic kinase Aurora-A.  


Elk-1 is a member of the E-twenty-six (ETS) domain superfamily of transcription factors and has been traditionally associated with mitogen-induced immediate early gene transcription upon phosphorylation by mitogen activated protein kinases (ERK/MAPK). Elk-1 is not only upregulated but also phosphorylated in brain tumour cells. However, in this study, we show for the first time that S383-phosphorylated Elk-1 (P-S383-Elk-1) is associated with mitotic spindle poles from metaphase through telophase and relocates to the spindle midbody during cytokinesis, while Thr417Ala mutation is associated with DNA throughout mitosis. Serine 383 phosphorylation appears to be important for polar localization of Elk-1, since exogenous protein including serine-to-alanine mutation was seen to be distributed throughout the spindle fibres. We further show that Elk-1 interacts with the cell cycle kinase Aurora-A, and when Aurora inhibitors are used, P-S383-Elk-1 fails to localize to the poles and remains associated with DNA. Apart from one transcriptional repressor molecule, Kaiso, this is the first time a transactivator was shown to possess such mitotic localization and interaction. The functional significance and detailed mechanism of this cell cycle-related localization of Elk-1 are yet to be determined. PMID:23322625

Demir, Ozlem; Kurnaz, Isil Aksan



Variation in sensitivity to. gamma. -ray-induced chromosomal aberrations during the mitotic cycle of the sea urchin egg  

SciTech Connect

Sea urchin eggs were irradiated with /sup 137/Cs ..gamma.. rays at various stages of the mitotic cycle, and chromosomal aberrations at the first postirradiation mitosis and embryonic abnormalities at later developmental stages were examined. The radiosensitivity of the eggs to both endpoints varied in parallel with the mitotic stage at the time of irradiation, suggesting a possible relationship between chromosomal damage and embryonic abnormalities.

Ejima, Y. (Univ. of Tokyo, Japan); Nakamura, I.; Shiroya, T.



RBPJ, the Major Transcriptional Effector of Notch Signaling, Remains Associated with Chromatin throughout Mitosis, Suggesting a Role in Mitotic Bookmarking  

PubMed Central

Mechanisms that maintain transcriptional memory through cell division are important to maintain cell identity, and sequence-specific transcription factors that remain associated with mitotic chromatin are emerging as key players in transcriptional memory propagation. Here, we show that the major transcriptional effector of Notch signaling, RBPJ, is retained on mitotic chromatin, and that this mitotic chromatin association is mediated through the direct association of RBPJ with DNA. We further demonstrate that RBPJ binds directly to nucleosomal DNA in vitro, with a preference for sites close to the entry/exit position of the nucleosomal DNA. Genome-wide analysis in the murine embryonal-carcinoma cell line F9 revealed that roughly 60% of the sites occupied by RBPJ in asynchronous cells were also occupied in mitotic cells. Among them, we found that a fraction of RBPJ occupancy sites shifted between interphase and mitosis, suggesting that RBPJ can be retained on mitotic chromatin by sliding on DNA rather than disengaging from chromatin during mitotic chromatin condensation. We propose that RBPJ can function as a mitotic bookmark, marking genes for efficient transcriptional activation or repression upon mitotic exit. Strikingly, we found that sites of RBPJ occupancy were enriched for CTCF-binding motifs in addition to RBPJ-binding motifs, and that RBPJ and CTCF interact. Given that CTCF regulates transcription and bridges long-range chromatin interactions, our results raise the intriguing hypothesis that by collaborating with CTCF, RBPJ may participate in establishing chromatin domains and/or long-range chromatin interactions that could be propagated through cell division to maintain gene expression programs. PMID:24603501

Choi, Inchan; Won, Kyoung-Jae; Fan, Hua-Ying



Hydroxyl free radicals generated by vanadyl[IV] induce cell blebbing in mitotic human Chang liver cells  

Microsoft Academic Search

Vanadium has recently been reported to induce interphase and M-phase (mitotic) programmed cell death via the generation of hydroxyl free radicals (OH*). In this paper, the effects of antioxidants on: (a) vanadyl[IV]-generated OH* free radical levels; and (b) cellular glutathione in vanadyl [IV]-treated Chang liver cells were evaluated. The surface morphology of vanadyl-treated mitotic cells was studied by confocal and

Boon-Huat Bay; Kwok-Hung Sit; Ramanujam Paramanantham; Yee-Gek Chan



Structural differentiation of the meiotic and mitotic chromosomes of the salamander, Ambystoma macrodactylum  

Microsoft Academic Search

The lampbrush chromosomes of the long-toed salamander, Ambystoma macrodactylum Baird, have been analysed and a map of the oocyte genome prepared. The location of C-bands and cold-induced-constrictions has been established in mitotic chromosomes and compared with the location of marker structures and chiasmata in several lampbrush bivalents. In the lampbrush chromosomes, C-bands are tentatively correlated with sphere-organizing loci and with

James Kezer; Pedro E. León



Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer  

Microsoft Academic Search

Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase–polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was

Y Nakamura; F Tanaka; N Haraguchi; K Mimori; T Matsumoto; H Inoue; K Yanaga; M Mori



Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A  

Microsoft Academic Search

The activity of the kinase Aurora-A (Aur-A) peaks during mitosis and depends on phosphorylation by one or more unknown kinases. Mitotic phosphorylation sites were mapped by mass spec sequencing of recombinant Aur-A protein that had been activated by incubation in extracts of metaphase-arrested Xenopus eggs. Three sites were identified: serine 53 (Ser-53), threonine 295 (Thr-295), and serine 349 (Ser-349), which

Laurie E. Littlepage; Hua Wu; Thorkell Andresson; Julia K. Deanehan; Laufey T. Amundadottir; Joan V. Ruderman



Comparative Analysis of Proliferating Cell Nuclear Antigen, Bromodeoxyuridine, and Mitotic Index in Uveal Melanoma  

Microsoft Academic Search

Purpose. Recent production of a monoclonal antibody, PC10, against proliferating cell nuclear antigen (PCNA) makes it possible to evaluate cell cycling in formalin-fixed tissues. In this study, the authors quantitatively evaluated the relationship between PCNA expression and two other measures of cell cycling, bromodeoxyuridine labeling index (BrdU LI) and mitotic index (MI), in archival uveal melanomas. The authors also examined

Siavash Ghazvini; Stewart Kroll; Devron H. Char; Hilary Frigillana


Cytological effects of Argemone oil on the mitotic cells of Allium cepa  

Microsoft Academic Search

The cytological effects of Argemone oil, which is one of the adulterants of edible oils, on the mitotic cells ofAllium cepa, have been investigated in detail following a treatment for one hour at different concentrations and also after recovery\\u000a for 24, 48 and 72 hours. Large number of cells have been scored and aberrations such as chromosome erosions, breakages, fragmentations,

S. Subramanyam; P. Venkat Reddy; G. Prem Veer Reedy; Dwarkanath K. Murthy



Mitotic Kinesin-Like Protein 2 Binds and Colocalizes with Papillomavirus E2 during Mitosis  

Microsoft Academic Search

MKlp2 is a kinesin-like motor protein of the central mitotic spindle required for completion of cytokinesis. Papillomavirus E2 is a sequence specific DNA binding protein that regulates viral transcription and replica- tion and is responsible for partitioning viral episomes into daughter cells during cell division. We demonstrate that MKlp2 specifically associates with the E2 protein during mitosis. Using chromatin immunoprecipitation,

Ting Yu; Yu-Cai Peng; Elliot J. Androphy



Pb-inhibited mitotic activity in onion roots involves DNA damage and disruption of oxidative metabolism.  


Plant responses to abiotic stress significantly affect the development of cells, tissues and organs. However, no studies correlating Pb-induced mitotic inhibition and DNA damage and the alterations in redox homeostasis during root division per se were found in the literature. Therefore, an experiment was conducted to evaluate the impact of Pb on mitotic activity and the associated changes in the oxidative metabolism in onion roots. The cytotoxic effect of Pb on cell division was assessed in the root meristems of Allium cepa (onion). The mitotic index (MI) was calculated and chromosomal abnormalities were sought. Pb-treatment induced a dose-dependent decrease in MI in the onion root tips and caused mitotic abnormalities such as distorted metaphase, fragments, sticky chromosomes, laggards, vagrant chromosomes and bridges. Single Cell Gel Electrophoresis was also performed to evaluate Pb induced genotoxicity. It was accompanied by altered oxidative metabolism in the onion root tips suggesting the interference of Pb with the redox homeostasis during cell division. There was a higher accumulation of malondialdehyde, conjugated dienes and hydrogen peroxide, and a significant increase in the activities of superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases in Pb-treated onion roots, whereas catalases activity exhibited a decreasing pattern upon Pb exposure. The study concludes that Pb-induced cytotoxicity and genotoxicity in the onion roots is mediated through ROS and is also tightly linked to the cell cycle. The exposure to higher concentrations arrested cell cycle leading to cell death, whereas different repair responses are generated at lower concentrations, thereby allowing the cell to complete the cell cycle. PMID:25023386

Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar



Argonaute-1 functions as a mitotic regulator by controlling Cyclin B during Drosophila early embryogenesis.  


The role of Ago-1 in microRNA (miRNA) biogenesis has been thoroughly studied, but little is known about its involvement in mitotic cell cycle progression. In this study, we established evidence of the regulatory role of Ago-1 in cell cycle control in association with the G2/M cyclin, cyclin B. Immunostaining of early embryos revealed that the maternal effect gene Ago-1 is essential for proper chromosome segregation, mitotic cell division, and spindle fiber assembly during early embryonic development. Ago-1 mutation resulted in the up-regulation of cyclin B-Cdk1 activity and down-regulation of p53, grp, mei-41, and wee1. The increased expression of cyclin B in Ago-1 mutants caused less stable microtubules and probably does not produce enough force to push the nuclei to the cortex, resulting in a decreased number of pole cells. The role of cyclin B in mitotic defects was further confirmed by suppressing the defects in the presence of one mutant copy of cyclin B. We identified involvement of 2 novel embryonic miRNAs--miR-981 and miR--317-for spatiotemporal regulation of cyclin B. In summary, our results demonstrate that the haploinsufficiency of maternal Ago-1 disrupts mitotic chromosome segregation and spindle fiber assembly via miRNA-guided control during early embryogenesis in Drosophila. The increased expression of cyclin B-Cdk1 and decreased activity of the Cdk1 inhibitor and cell cycle checkpoint proteins (mei-41 and grp) in Ago-1 mutant embryos allow the nuclei to enter into mitosis prematurely, even before completion of DNA replication. Thus, our results have established a novel role of Ago-1 as a regulator of the cell cycle. PMID:24165481

Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Bag, Indira; Hunt, Clayton R; Ramaiah, M Janaki; Pandita, Tej K; Bhadra, Utpal; Pal-Bhadra, Manika



Differential staining and chromatin packing of the mitotic chromosomes of the newt Triturus cristatus  

Microsoft Academic Search

Mitotic metaphase chromosomes of cold-treated Triturus cristatus show a characteristic pattern of constrictions, most of which lie close, though not immediately adjacent, to the centromeres. The chromatin in these cold-induced constrictions stains intensely with Giemsa. Cold-treated spermatogonia show spiral structure throughout the metaphase chromatids; the packing of chromatin fibrils is much tighter in the constricted regions than elsewhere, and the

Edwina Rudak; H. G. Callan



Expression, regulation and activity of a B2-type cyclin in mitotic and endoreduplicating maize endosperm  

PubMed Central

Cyclin-dependent kinases, the master regulators of the eukaryotic cell cycle, are complexes comprised of a catalytic serine/threonine protein kinase and an essential regulatory cyclin. The maize genome encodes over 50 cyclins grouped in different types, but they have been little investigated. We characterized a type B2 cyclin (CYCB2;2) during maize endosperm development, which comprises a cell proliferation phase based on the standard mitotic cell cycle, followed by an endoreduplication phase in which DNA replication is reiterated in the absence of mitosis or cytokinesis. CYCB2;2 RNA was present throughout the period of endosperm development studied, but its level declined as the endosperm transitioned from a mitotic to an endoreduplication cell cycle. However, the level of CYCB2;2 protein remained relatively constant during both stages of endosperm development. CYCB2;2 was recalcitrant to degradation by the 26S proteasome in endoreduplicating endosperm extracts, which could explain its sustained accumulation during endosperm development. In addition, although CYCB2;2 was generally localized to the nucleus of endosperm cells, a lower molecular weight form of the protein accumulated specifically in the cytosol of endoreduplicating endosperm cells. In dividing cells, CYCB2;2 appeared to be localized to the phragmoplast and may be involved in cytokinesis and cell wall formation. Kinase activity was associated with CYCB2;2 in mitotic endosperm, but was absent or greatly reduced in immature ear and endoreduplicating endosperm. CYCB2;2-associated kinase phosphorylated maize E2F1 and the “pocket” domains of RBR1 and RBR3. CYCB2;2 interacted with both maize CDKA;1 and CDKA;3 in insect cells. These results suggest CYCB2;2 functions primarily during the mitotic cell cycle, and they are discussed in the context of the roles of cyclins, CDKs and proteasome activity in the regulation of the cell cycle during endosperm development. PMID:25368625

Sabelli, Paolo A.; Dante, Ricardo A.; Nguyen, Hong N.; Gordon-Kamm, William J.; Larkins, Brian A.



CHFR Protein Regulates Mitotic Checkpoint by Targeting PARP-1 Protein for Ubiquitination and Degradation*  

PubMed Central

The mitotic checkpoint gene CHFR (checkpoint with forkhead-associated (FHA) and RING finger domains) is silenced by promoter hypermethylation or mutated in various human cancers, suggesting that CHFR is an important tumor suppressor. Recent studies have reported that CHFR functions as an E3 ubiquitin ligase, resulting in the degradation of target proteins. To better understand how CHFR suppresses cell cycle progression and tumorigenesis, we sought to identify CHFR-interacting proteins using affinity purification combined with mass spectrometry. Here we show poly(ADP-ribose) polymerase 1 (PARP-1) to be a novel CHFR-interacting protein. In CHFR-expressing cells, mitotic stress induced the autoPARylation of PARP-1, resulting in an enhanced interaction between CHFR and PARP-1 and an increase in the polyubiquitination/degradation of PARP-1. The decrease in PARP-1 protein levels promoted cell cycle arrest at prophase, supporting that the cells expressing CHFR were resistant to microtubule inhibitors. In contrast, in CHFR-silenced cells, polyubiquitination was not induced in response to mitotic stress. Thus, PARP-1 protein levels did not decrease, and cells progressed into mitosis under mitotic stress, suggesting that CHFR-silenced cancer cells were sensitized to microtubule inhibitors. Furthermore, we found that cells from Chfr knockout mice and CHFR-silenced primary gastric cancer tissues expressed higher levels of PARP-1 protein, strongly supporting our data that the interaction between CHFR and PARP-1 plays an important role in cell cycle regulation and cancer therapeutic strategies. On the basis of our studies, we demonstrate a significant advantage for use of combinational chemotherapy with PARP inhibitors for cancer cells resistant to microtubule inhibitors. PMID:22337872

Kashima, Lisa; Idogawa, Masashi; Mita, Hiroaki; Shitashige, Miki; Yamada, Tesshi; Ogi, Kazuhiro; Suzuki, Hiromu; Toyota, Minoru; Ariga, Hiroyoshi; Sasaki, Yasushi; Tokino, Takashi



Rapid preparation of the mitotic kinesin Eg5 inhibitor monastrol using controlled microwave-assisted synthesis  

Microsoft Academic Search

We present here a protocol for the synthesis of the dihydropyrimidine (DHPM) derivative monastrol, which is known to be a specific mitotic kinesin Eg5 inhibitor. By applying controlled microwave heating under sealed-vessel conditions, the synthesis via the one-pot three-component Biginelli condensation can be performed in a shorter reaction time (30 min) compared with conventional heating methods that normally require several

Doris Dallinger; C Oliver Kappe



AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol  

Microsoft Academic Search

The serine-threonine kinase gene AURORA-A is commonly amplified in epithelial malignancies. Here we show that elevated Aurora-A expression at levels that reflect cancer-associated gene amplification overrides the checkpoint mechanism that monitors mitotic spindle assembly, inducing resistance to the chemotherapeutic agent paclitaxel (Taxol). Cells overexpressing Aurora-A inappropriately enter anaphase despite defective spindle formation, and the persistence of Mad2 at the kinetochores,

Shubha Anand; Sue Penrhyn-Lowe; Ashok R Venkitaraman



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

PubMed Central

Background During the last three decades, the cell cycle and its control by cyclin-dependent kinases (CDKs) have been extensively studied in eukaryotes. This endeavour has produced an overall picture that basic mechanisms seem to be largely conserved among all eukaryotes. The intricate regulation of CDK activities includes, among others, CDK activation by CDC25 phosphatase at G2/M. In plants, however, studies of this regulation have lagged behind as a plant Cdc25 homologue or other unrelated phosphatase active at G2/M have not yet been identified. Scope Failure to identify a plant mitotic CDK activatory phosphatase led to characterization of the effects of alien cdc25 gene expression in plants. Tobacco, expressing the Schizosaccharomyces pombe mitotic activator gene, Spcdc25, exhibited morphological, developmental and biochemical changes when compared with wild type (WT) and, importantly, increased CDK dephosphorylation at G2/M. Besides changes in leaf shape, internode length and root development, in day-neutral tobacco there was dramatically earlier onset of flowering with a disturbed acropetal floral capacity gradient typical of WT. In vitro, de novo organ formation revealed substantially earlier and more abundant formation of shoot primordia on Spcdc25 tobacco stem segments grown on shoot-inducing media when compared with WT. Moreover, in contrast to WT, stem segments from transgenic plants formed shoots even without application of exogenous growth regulator. Spcdc25-expressing BY-2 cells exhibited a reduced mitotic cell size due to a shortening of the G2 phase together with high activity of cyclin-dependent kinase, NtCDKB1, in early S-phase, S/G2 and early M-phase. Spcdc25-expressing tobacco (‘Samsun’) cell suspension cultures showed a clustered, more circular, cell phenotype compared with chains of elongated WT cells, and increased content of starch and soluble sugars. Taken together, Spcdc25 expression had cytokinin-like effects on the characteristics studied, although determination of endogenous cytokinin levels revealed a dramatic decrease in Spcdc25 transgenics. Conclusions The data gained using the plants expressing yeast mitotic activator, Spcdc25, clearly argue for the existence and importance of activatory dephosphorylation at G2/M transition and its interaction with cytokinin signalling in plants. The observed cytokinin-like effects of Spcdc25 expression are consistent with the concept of interaction between cell cycle regulators and phytohormones during plant development. The G2/M control of the plant cell cycle, however, remains an elusive issue as doubts persist about the mode of activatory dephosphorylation, which in other eukaryotes is provided by Cdc25 phosphatase serving as a final all-or-nothing mitosis regulator. PMID:21339187

Lipavská, Helena; Mašková, Petra; Vojvodová, Petra



Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe.  


Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis. PMID:25275596

Cornago, M; Garcia-Alberich, C; Blasco-Angulo, N; Vall-Llaura, N; Nager, M; Herreros, J; Comella, J X; Sanchis, D; Llovera, M



Herbimycin A suppresses mitotic activity and egg production of female Schistosoma mansoni.  


The eggs of the endoparasite Schistosoma are the causative agent of schistosomiasis, an important disease of humans, which is endemic in (sub-) tropical regions. The absence of a vaccine with sufficient protective qualities and increasing resistance to approved and established drugs like praziquantel, justify the exploration of novel ways to fight schistosomes. Our strategy is based on interference with the sexual maturation of the female. Prerequisites for gonad development in adult females are a continuous pairing contact with the male and significantly increased mitotic activity. In this study we show that the male governs sexual maturation of the female, as the separation of couples causes a clear reduction of female mitotic activity and, consequently, egg production. We demonstrate that treatment of schistosomes with Herbimycin A, an inhibitor of protein tyrosine kinases (PTKs), mimics the separation of couples as the drug blocks mitotic activity and egg production of paired females. However, the synthesis of the eggshell precursor protein p14 is elevated. Furthermore, we show for the first time in invertebrates that Herbimycin A decreases tyrosine phosphorylation and PTK stability in schistosomes. Summarised, our data provide evidence that PTKs have key functions in regulating gonad development, eggshell gene expression and, consequently, egg production. Therefore, we suggest envisaging schistosome PTKs as novel targets for strategies to combat schistosomiasis. PMID:16844129

Knobloch, Jürgen; Kunz, Werner; Grevelding, Christoph G



Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe  

PubMed Central

Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis. PMID:25275596

Cornago, M; Garcia-Alberich, C; Blasco-Angulo, N; Vall-llaura, N; Nager, M; Herreros, J; Comella, J X; Sanchis, D; Llovera, M



Polycystic kidney disease protein fibrocystin localizes to the mitotic spindle and regulates spindle bipolarity.  


Autosomal recessive polycystic kidney disease (ARPKD) is a significant hereditary renal disease occurring in infancy and childhood, which presents with greatly enlarged echogenic kidneys, ultimately leading to renal insufficiency and end-stage renal disease. ARPKD is caused by mutations in a single gene PKHD1, which encodes fibrocystin/polyductin (FPC), a large single transmembrane protein generally known to be on the primary cilium, basal body and plasma membrane. Here, using our newly generated antibody raised against the entire C-terminal intracellular cytoplasmic domain (ICD) of FPC, as well as our previously well-characterized antibody against a peptide of ICD, we report for the first time that at least one isoform of FPC is localized to the centrosome and mitotic spindle of dividing cells in multiple cell lines, including MDCK, mIMCD3, LLC-PK1, HEK293, RCTEC and HFCT cells. Using short-hairpin-mediated RNA interference, we show that the inhibition of FPC function in MDCK and mIMCD3 cells leads to centrosome amplification, chromosome lagging and multipolar spindle formation. Consistent with our in vitro findings, we also observed centrosome amplification in the kidneys from human ARPKD patients. These findings demonstrate a novel function of FPC in centrosome duplication and mitotic spindle assembly during cell division. We propose that mitotic defects due to FPC dysfunction contribute to cystogenesis in ARPKD. PMID:20554582

Zhang, Jingjing; Wu, Maoqing; Wang, Shixuan; Shah, Jagesh V; Wilson, Patricia D; Zhou, Jing



PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator  

PubMed Central

dsRNA-dependent protein kinase R (PKR) is a ubiquitously expressed enzyme well known for its roles in immune response. Upon binding to viral dsRNA, PKR undergoes autophosphorylation, and the phosphorylated PKR (pPKR) regulates translation and multiple signaling pathways in infected cells. Here, we found that PKR is activated in uninfected cells, specifically during mitosis, by binding to dsRNAs formed by inverted Alu repeats (IRAlus). While PKR and IRAlu-containing RNAs are segregated in the cytosol and nucleus of interphase cells, respectively, they interact during mitosis when nuclear structure is disrupted. Once phosphorylated, PKR suppresses global translation by phosphorylating the ? subunit of eukaryotic initiation factor 2 (eIF2?). In addition, pPKR acts as an upstream kinase for c-Jun N-terminal kinase and regulates the levels of multiple mitotic factors such as CYCLINS A and B and POLO-LIKE KINASE 1 and phosphorylation of HISTONE H3. Disruption of PKR activation via RNAi or expression of a transdominant-negative mutant leads to misregulation of the mitotic factors, delay in mitotic progression, and defects in cytokinesis. Our study unveils a novel function of PKR and endogenous dsRNAs as signaling molecules during the mitosis of uninfected cells. PMID:24939934

Kim, Yoosik; Lee, Jung Hyun; Park, Jong-Eun; Cho, Jun; Yi, Hyerim; Kim, V. Narry



Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration  

PubMed Central

The nuclear import receptors importin ? and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin ? is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin ? for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin ?, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin ? and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. PMID:24478460

Bernis, Cyril; Swift-Taylor, Beth; Nord, Matthew; Carmona, Sarah; Chook, Yuh Min; Forbes, Douglass J.



Aurora B-dependent regulation of class IIa histone deacetylases by mitotic nuclear localization signal phosphorylation.  


Class IIa histone deacetylases (HDACs 4/5/7/9) are transcriptional regulators with critical roles in cardiac disease and cancer. HDAC inhibitors are promising anticancer agents, and although they are known to disrupt mitotic progression, the underlying mechanisms of mitotic regulation by HDACs are not fully understood. Here we provide the first identification of histone deacetylases as substrates of Aurora B kinase (AurB). Our study identifies class IIa HDACs as a novel family of AurB targets and provides the first evidence that HDACs are temporally and spatially regulated by phosphorylation during the cell cycle. We define the precise site of AurB-mediated phosphorylation as a conserved serine within the nuclear localization signals of HDAC4, HDAC5, and HDAC9 at Ser265, Ser278, and Ser242, respectively. We establish that AurB interacts with these HDACs in vivo, and that this association increases upon disruption of 14-3-3 binding. We observe colocalization of endogenous, phosphorylated HDACs with AurB at the mitotic midzone in late anaphase and the midbody during cytokinesis, complemented by a reduction in HDAC interactions with components of the nuclear corepressor complex. We propose that AurB-dependent phosphorylation of HDACs induces sequestration within a phosphorylation gradient at the midzone, maintaining separation from re-forming nuclei and contributing to transcriptional control. PMID:22865920

Guise, Amanda J; Greco, Todd M; Zhang, Irene Y; Yu, Fang; Cristea, Ileana M



Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase activation in budding yeast.  


Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. Initial Net1 phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14 Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN) signaling cascade maintains Cdc14 release. An important unresolved question is how Cdc14 activity can increase in early anaphase, while Cdk activity, that is required for Net1 phosphorylation, decreases and the MEN is not yet active. Here we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in early anaphase, relieving the inhibition and promoting further Cdc14 release. Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14 phosphatase activation during mitotic exit, required for faithful chromosome segregation and completion of the cell division cycle. PMID:25569132

Godfrey, Molly; Kuilman, Thomas; Uhlmann, Frank



Aurora Kinases Phosphorylate Lgl to Induce Mitotic Spindle Orientation in Drosophila Epithelia  

PubMed Central

Summary The Lethal giant larvae (Lgl) protein was discovered in Drosophila as a tumor suppressor in both neural stem cells (neuroblasts) and epithelia. In neuroblasts, Lgl relocalizes to the cytoplasm at mitosis, an event attributed to phosphorylation by mitotically activated aPKC kinase and thought to promote asymmetric cell division. Here we show that Lgl also relocalizes to the cytoplasm at mitosis in epithelial cells, which divide symmetrically. The Aurora A and B kinases directly phosphorylate Lgl to promote its mitotic relocalization, whereas aPKC kinase activity is required only for polarization of Lgl. A form of Lgl that is a substrate for aPKC, but not Aurora kinases, can restore cell polarity in lgl mutants but reveals defects in mitotic spindle orientation in epithelia. We propose that removal of Lgl from the plasma membrane at mitosis allows Pins/LGN to bind Dlg and thus orient the spindle in the plane of the epithelium. Our findings suggest a revised model for Lgl regulation and function in both symmetric and asymmetric cell divisions. PMID:25484300

Bell, Graham P.; Fletcher, Georgina C.; Brain, Ruth; Thompson, Barry J.



Notch inhibition induces mitotically generated hair cells in mammalian cochleae via activating the Wnt pathway.  


The activation of cochlear progenitor cells is a promising approach for hair cell (HC) regeneration and hearing recovery. The mechanisms underlying the initiation of proliferation of postnatal cochlear progenitor cells and their transdifferentiation to HCs remain to be determined. We show that Notch inhibition initiates proliferation of supporting cells (SCs) and mitotic regeneration of HCs in neonatal mouse cochlea in vivo and in vitro. Through lineage tracing, we identify that a majority of the proliferating SCs and mitotic-generated HCs induced by Notch inhibition are derived from the Wnt-responsive leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5(+)) progenitor cells. We demonstrate that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5(+) progenitor cells to mitotically generate new HCs. Our study reveals a new function of Notch signaling in limiting proliferation and regeneration potential of postnatal cochlear progenitor cells, and provides a new route to regenerate HCs from progenitor cells by interrupting the interaction between the Notch and Wnt pathways. PMID:25535395

Li, Wenyan; Wu, Jingfang; Yang, Jianming; Sun, Shan; Chai, Renjie; Chen, Zheng-Yi; Li, Huawei



Population dynamics of a meiotic/mitotic expansion model for the fragile X syndrome  

SciTech Connect

A model to explain the mutational process and population dynamics of the fragile X syndrome is presented. The mutational mechanism was assumed to be a multi-pathway, multistep process. Expansion of CGG repeats was based on an underlying biological process and was assumed to occur at two time points: meiosis and early embryonic development (mitosis). Meiotic expansion was assumed to occur equally in oogenesis and spermatogenesis, while mitotic expansion was restricted to somatic, or constitutional, alleles of maternal origin. Testable hypotheses were predicted by this meiotic/mitotic model. First, parental origin of mutation is predicted to be associated with the risk of a woman to have a full-mutation child. Second, {open_quotes}contractions{close_quotes} seen in premutation male transmissions are predicted not to be true contractions in repeat size, but a consequence of the lack of mitotic expansion in paternally derived alleles. Third, a portion of full-mutation males should have full-mutation alleles in their sperm, due to the lack of complete selection against the full-mutation female. Fourth, a specific premutation-allele frequency distribution is predicted and differs from that based on models assuming only meiotic expansion. Last, it is predicted that {approximately}65 generations are required to achieve equilibrium, but this depends greatly on the expansion probabilities. 42 refs., 4 figs., 4 tabs.

Ashley, A.E.; Sherman, S.L. [Emory Univ. School of Medicine, Atlanta, GA (United States)



CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint.  


How the state of spindle microtubule capture at the kinetochore is translated into mitotic checkpoint signaling remains largely unknown. In this paper, we demonstrate that the kinetochore-associated mitotic kinase BubR1 phosphorylates itself in human cells and that this autophosphorylation is dependent on its binding partner, the kinetochore motor CENP-E. This CENP-E-dependent BubR1 autophosphorylation at unattached kinetochores is important for a full-strength mitotic checkpoint to prevent single chromosome loss. Replacing endogenous BubR1 with a nonphosphorylatable BubR1 mutant, as well as depletion of CENP-E, the BubR1 kinase activator, results in metaphase chromosome misalignment and a decrease of Aurora B-mediated Ndc80 phosphorylation at kinetochores. Furthermore, expressing a phosphomimetic BubR1 mutant substantially reduces the incidence of polar chromosomes in CENP-E-depleted cells. Thus, the state of CENP-E-dependent BubR1 autophosphorylation in response to spindle microtubule capture by CENP-E is important for kinetochore function in achieving accurate chromosome segregation. PMID:22801780

Guo, Yige; Kim, Christine; Ahmad, Sana; Zhang, Jiayin; Mao, Yinghui



Differing requirements for Augmin in male meiotic and mitotic spindle formation in Drosophila  

PubMed Central

Animal cells divide using a microtubule-based, bipolar spindle. Both somatic, mitotic cells and sperm-producing male meiotic spermatocytes use centrosome-dependent and acentrosomal spindle-forming mechanisms. Here, we characterize the largely undefined, centrosome-independent spindle formation pathway used during male meiosis. Our live and fixed cell analyses of Drosophila spermatocytes reveal that acentrosomal microtubules are nucleated at kinetochores and in the vicinity of chromatin and that together these assemble into functional spindles. Mutational studies indicate that ?-tubulin and its extra-centrosomal targeting complex, Augmin, are vital for this process. In addition, Augmin facilitates efficient spindle assembly in the presence of centrosomes. In contrast to the pronounced recruitment of Augmin on spindles in other cell types, the complex is absent from those of spermatocytes but does accumulate on kinetochores. Polo kinase facilitates this kinetochore recruitment while inhibiting Augmin's spindle association, and this in turn dictates ?-tubulin distribution and spindle density. Polo's negative regulation of Augmin in male meiosis contrasts with its requirement in loading Augmin along mitotic spindles in somatic Drosophila cells. Together our data identify a novel mechanism of acentrosomal spindle formation in spermatocytes and reveal its divergence from that used in mitotic cells. PMID:24829288

Savoian, Matthew S.; Glover, David M.



Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle.  


The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules. PMID:23516109

Hochegger, Helfrid; Hégarat, Nadia; Pereira-Leal, Jose B



A B-Myb complex containing clathrin and filamin is required for mitotic spindle function.  


B-Myb is one member of the vertebrate Myb family of transcription factors and is ubiquitously expressed. B-Myb activates transcription of a group of genes required for the G2/M cell cycle transition by forming the dREAM/Myb-MuvB-like complex, which was originally identified in Drosophila. Mutants of zebrafish B-myb and Drosophila myb exhibit defects in cell cycle progression and genome instability. Although the genome instability caused by a loss of B-Myb has been speculated to be due to abnormal cell cycle progression, the precise mechanism remains unknown. Here, we have purified a B-Myb complex containing clathrin and filamin (Myb-Clafi complex). This complex is required for normal localization of clathrin at the mitotic spindle, which was previously reported to stabilize kinetochore fibres. The Myb-Clafi complex is not tightly associated with the mitotic spindles, suggesting that this complex ferries clathrin to the mitotic spindles. Thus, identification of the Myb-Clafi complex reveals a previously unrecognized function of B-Myb that may contribute to its role in chromosome stability, possibly, tumour suppression. PMID:18548008

Yamauchi, Tomohiro; Ishidao, Takefumi; Nomura, Teruaki; Shinagawa, Toshie; Tanaka, Yasunori; Yonemura, Shigenobu; Ishii, Shunsuke



Nur1 Dephosphorylation Confers Positive Feedback to Mitotic Exit Phosphatase Activation in Budding Yeast  

PubMed Central

Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit. Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from which it is released in anaphase following Net1 phosphorylation. Initial Net1 phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14 Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN) signaling cascade maintains Cdc14 release. An important unresolved question is how Cdc14 activity can increase in early anaphase, while Cdk activity, that is required for Net1 phosphorylation, decreases and the MEN is not yet active. Here we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in early anaphase, relieving the inhibition and promoting further Cdc14 release. Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14 phosphatase activation during mitotic exit, required for faithful chromosome segregation and completion of the cell division cycle. PMID:25569132

Godfrey, Molly; Kuilman, Thomas; Uhlmann, Frank



Detection of mitotic and meiotic aneuploidy in the yeast Saccharomyces cerevisiae.  

PubMed Central

A number of genetic systems are described which involve the use of the yeast Saccharomyces cerevisiae. The systems may be used to detect the production of aneuploid cells produced during both mitotic and meiotic cell division in the presence of genetically active chemicals. During mitotic cell division, monosomic colonies (2n - 1) may be detected by plating upon selective medium. Increases in such monosomic colonies are produced by exposure of cells to a number of chemical mutagens such as ethyl methane-sulfonate and mitomycin C. More importantly, monosomic colonies are also induced by nonmutagens such as sulfacetamide and saccharin, which suggests that such chemicals are capable of inducing aneuploidy (aneugenic) in the absence of mutagenic activity. Genetic analysis of aneuploid colonies produced on nonselective medium indicate that at least a proportion of the monosomic colonies were the result of mitotic nondisjunction. During meiotic cell division, disomic cells (n + 1) produced by chromosome nondisjunction may be detected by plating on selective media. The frequency of disomic cells has been shown to increase after exposure to p-fluorophenylalanine. PMID:387403

Parry, J M; Sharp, D; Parry, E M



Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein.  


The mitotic checkpoint (or spindle assembly checkpoint) is a fail-safe mechanism to prevent chromosome missegregation by delaying anaphase onset in the presence of defective kinetochore-microtubule attachment. The target of the checkpoint is the E3 ubiquitin ligase anaphase-promoting complex/cyclosome. Once all chromosomes are properly attached and bioriented at the metaphase plate, the checkpoint needs to be silenced. Previously, we and others have reported that TRIP13 AAA-ATPase binds to the mitotic checkpoint-silencing protein p31(comet). Here we show that endogenous TRIP13 localizes to kinetochores. TRIP13 knockdown delays metaphase-to-anaphase transition. The delay is caused by prolonged presence of the effector for the checkpoint, the mitotic checkpoint complex, and its association and inhibition of the anaphase-promoting complex/cyclosome. These results suggest that TRIP13 is a novel mitotic checkpoint-silencing protein. The ATPase activity of TRIP13 is essential for its checkpoint function, and interference with TRIP13 abolished p31(comet)-mediated mitotic checkpoint silencing. TRIP13 overexpression is a hallmark of cancer cells showing chromosomal instability, particularly in certain breast cancers with poor prognosis. We suggest that premature mitotic checkpoint silencing triggered by TRIP13 overexpression may promote cancer development. PMID:25012665

Wang, Kexi; Sturt-Gillespie, Brianne; Hittle, James C; Macdonald, Dawn; Chan, Gordon K; Yen, Tim J; Liu, Song-Tao



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



Cellular and molecular effects of 1GeV/n iron ion exposure on post-mitotic human neurons  

NASA Astrophysics Data System (ADS)

During space travel, astronauts will be exposed to high energy, high atomic number (HZE) radiation. The potential for damage to cells of the central nervous system following exposure to HZE particle radiation has been characterized as a potential critical risk. Unfortunately, there are very few working model systems of human neurons and as a result, data describing the effects of HZE radiation on them is scarce. To begin risk assessment studies, we utilized an in vitro model consisting of terminally differentiated, post-mitotic human neurons (hNT cells). Previous studies have shown that transplantation of these cells into numerous rodent models of neurological diseases has resulted in successful mitigation of the related disorders, thereby demonstrating their functional relevance. Following exposure of these cells to 1GeV/n Fe ions at the NASA Space Radiation Laboratory, we measured the induction and repair of DNA damage (as revealed by g-H2AX foci), cytotoxicity, gene expression changes, and the induction of apoptosis and its pharmacological reduction. Fluorescence microscopy techniques revealed that there was a dose-dependent induction of g- H2AX foci in hNT cells, with a peak effect 4 hours after exposure (which is significantly longer than for reports using mitotic cells). DNA repair was evident in that the levels of g-H2AX foci were reduced to those in unirradiated cells by 24 hours post-irradiation. Cytotoxicity was also induced in a dose-dependent manner as detected by the fluorescent-based Live/Dead assay. Analysis of the status of the apoptosis-inducing gene p53 showed that the levels of this protein increased significantly 4-8 hours after exposure to Fe ions. By 3 days post-irradiation, annexin V staining demonstrated a dose-dependent induction of apoptosis in the hNT cells. Pre-treatment with two different concentrations of the growth factor TGF-b were effective in reducing the levels of Fe ion-induced apoptosis to statistically significant degrees.

Guida, Peter; Vazquez, Marcelo E.; Guida, Peter; Kim, Angela


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