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Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
Luigi Scotto, Gopeshwar Narayan, Subhadra V Nandula, Shivakumar Subramaniyam, Andreas M Kaufmann, Jason D Wright, Bhavana Pothuri, Mahesh Mansukhani, Achim Schneider, Hugo Arias-Pulido, Vundavalli V Murty
Molecular Cancer , 2008, DOI: 10.1186/1476-4598-7-58
Abstract: To examine the role of 5p gain, we performed a combination of single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression analyses on invasive cancer and in various stages of CC progression.The SNP and FISH analyses revealed copy number increase (CNI) of 5p in 63% of invasive CC, which arises at later stages of precancerous lesions in CC development. We integrated chromosome 5 genomic copy number and gene expression data to identify key target over expressed genes as a consequence of 5p gain. One of the candidates identified was Drosha (RNASEN), a gene that is required in the first step of microRNA (miRNA) processing in the nucleus. Other 5p genes identified as targets of CNI play a role in DNA repair and cell cycle regulation (BASP1, TARS, PAIP1, BRD9, RAD1, SKP2, and POLS), signal transduction (OSMR), and mitochondrial oxidative phosphorylation (NNT, SDHA, and NDUFS6), suggesting that disruption of pathways involving these genes may contribute to CC progression.Taken together, we demonstrate the power of integrating genomics data with expression data in deciphering tumor-related targets of CNI. Identification of 5p gene targets in CC denotes an important step towards biomarker development and forms a framework for testing as molecular therapeutic targets.The short arm of chromosome 5 (5p) frequently undergoes nonrandom changes in cervical cancer (CC) by exhibiting both copy number increase and deletions. Gain of 5p due to frequent appearance of isochromosome 5p in squamous cell carcinoma has been documented by karyotypic and chromosomal comparative genomic hybridization analyses [1-4]. Paradoxically, 5p also exhibits frequent loss of heterozygosity, which occurs early in the development of CC [5,6]. These findings suggest the presence of important proliferation-regulating genes on chromosome 5p involved in malignant progression of cervical epithelium.Despite the successful use of pap-smear screening programs in early
ALPHA IMPORTANCE OF MENTORING PROGRAMME 5P IN CARE
Koubová ?árka,B?ízová Bohdana
Aktuální Otázky Sociální Politiky : Teorie a Praxe , 2012,
Abstract: Alpha The programme 5P is mentoring program that is implemented in theCzech Republic since 1996. The following range of programs for children at risk for an individual relationship with an adult mentor. The greatest benefit was for children enrolled in the programme 5P registered in confidence, social adaptation and theirability to express their feelings.
Analysis of Dependencies of Checkpoint Cost and Checkpoint Interval of Fault Tolerant MPI Applications
Mallikarjuna Shastry P.M,K. Venkatesh
International Journal on Computer Science and Engineering , 2010,
Abstract: In this paper, we have analysed i) the relationship between the checkpoint cost and the optimal checkpoint interval and ii) the relationship between the checkpoint cost and the number of processors (processes) and we have also determined the optimal number ofprocessors (processes) required for executing the fault tolerant MPI applications. We have presented an experimental study in which, wehave used an optimal checkpoint restart model [1] with Weibull’s and Exponential distributions to determine the optimal checkpoint nterval. We have observed that, the optimal checkpoint intervalsobtained using Weibull’s distribution, produce minimal average completion time; as compared with the optimal checkpoint intervals obtained using Exponential distribution. The optimal checkpoint interval is approximately directly proportional to the checkpoint cost and inversely proportional to shape parameter. The study indicates that, the checkpoint cost of MPI applications increases with the number of processors (processes) used for execution.We have determined the optimal number of processes (processors) required to execute the MPI applications considered in this paper, as 4.
The helium-rich cataclysmic variable SBSS 1108+574  [PDF]
P. J. Carter,D. Steeghs,E. de Miguel,W. Goff,R. A. Koff,T. Krajci,T. R. Marsh,B. T. G?nsicke,E. Breedt,P. J. Groot,G. Nelemans,G. H. A. Roelofs,A. Rau,D. Koester,T. Kupfer
Physics , 2013, DOI: 10.1093/mnras/stt169
Abstract: We present time-resolved spectroscopy and photometry of the dwarf nova SBSS 1108+574, obtained during the 2012 outburst. Its quiescent spectrum is unusually rich in helium, showing broad, double-peaked emission lines from the accretion disc. We measure a line flux ratio HeI 5875/Halpha = 0.81 +/- 0.04, a much higher ratio than typically observed in cataclysmic variables (CVs). The outburst spectrum shows hydrogen and helium in absorption, with weak emission of Halpha and HeI 6678, as well as strong HeII emission. From our photometry, we find the superhump period to be 56.34 +/- 0.18 minutes, in agreement with the previously published result. The spectroscopic period, derived from the radial velocities of the emission lines, is found to be 55.3 +/- 0.8 minutes, consistent with a previously identified photometric orbital period, and significantly below the normal CV period minimum. This indicates that the donor in SBSS 1108+574 is highly evolved. The superhump excess derived from our photometry implies a mass ratio of q = 0.086 +/- 0.014. Our spectroscopy reveals a grazing eclipse of the large outbursting disc. As the disc is significantly larger during outburst, it is unlikely that an eclipse will be detectable in quiescence. The relatively high accretion rate implied by the detection of outbursts, together with the large mass ratio, suggests that SBSS 1108+574 is still evolving towards its period minimum.
Worm reanimation checkpoint
David Secko
Genome Biology , 2003, DOI: 10.1186/gb-spotlight-20031107-03
Abstract: Nystul et al. used RNA interference (RNAi) to test 2445 open reading frames (ORFs) for involvement in anoxia-induced suspended animation, and they identified an ORF that caused C. elegans embryos to lose viability upon exposure to anoxia. The gene was subsequently named san-1 - for suspended animation 1 - and was observed to be specifically required for anoxia-induced suspended animation, since its loss had no effect on viability under normal conditions (normoxia) or less severe oxygen depletion (hypoxia). The homology of the SAN-1 protein suggested it could be a spindle checkpoint component, and it was subsequently shown to be localized to the poleward faces of chromosomes during metaphase. SAN-1 was also shown to be necessary for nocodazole-induced spindle checkpoint activity, suggesting that spindle checkpoint components were necessary for suspended animation.The authors then monitored wildtype embryos during anoxia and observed that metaphase increased from 18.2% in normoxia to 42.9% in anoxia. In san-1(RNAi) embryos metaphase decreased to 0.7%, and the embryos showed missegregation of chromosomes and aneuploidy, demonstrating that san-1 was required for an increase in metaphase, "providing a compelling explanation for the anoxia-specific lethality in san-1(RNAi)" embryos."We have demonstrated that san-1 is a component of the spindle checkpoint in C. elegans and that activation of the spindle checkpoint is essential for successful execution of the suspended animation program," conclude the authors.
Near-infrared Observations of Nova V574 Puppis (2004)  [PDF]
Sachindra Naik,Dipankar P. K. Banerjee,N. M. Ashok,R. K. Das
Physics , 2010, DOI: 10.1111/j.1365-2966.2010.16292.x
Abstract: We present results obtained from extensive near-infrared spectroscopic and photometric observations of nova V574 Pup during its 2004 outburst. The observations were obtained over four months, starting from 2004 November 25 (four days after the nova outburst) to 2005 March 20. The near-IR JHK light curve is presented - no evidence is seen from it for dust formation to have occurred during our observations. In the early decline phase, the JHK spectra of the nova are dominated by emission lines of hydrogen Brackett and Paschen series, OI, CI and HeI. We also detect the fairly uncommon Fe II line at 1.6872 micron in the early part of our observations. The strengths of the HeI lines at 1.0830 micron and 2.0585 micron are found to become very strong towards the end of the observations indicating a progression towards higher excitation conditions in the nova ejecta. The width of the emission lines do not show any significant change during the course of our observations. The slope of the continuum spectrum was found to have a lambda^{-2.75} dependence in the early stages which gradually becomes flatter with time and changes to a free-free spectral dependence towards the later stages. Recombination analysis of the HI lines shows deviations from Case B conditions during the initial stages. However, towards the end of our observations, the line strengths are well simulated with case B model values with electron density n_e = 10^{9-10} cm^{-3} and a temperature equal to 10^4 K. Based on our distance estimate to the nova of 5.5 kpc and the observed free-free continuum emission in the later part of the observations, we estimate the ionized mass of the ejecta to be between 10^{-5} and 10^{-6} solar-mass.
GRID COMPUTING AND CHECKPOINT APPROACH  [PDF]
Pankaj gupta
International Journal of Computer Science and Management Studies , 2011,
Abstract: Grid computing is a means of allocating the computational power of alarge number of computers to complex difficult computation or problem. Grid computing is a distributed computing paradigm thatdiffers from traditional distributed computing in that it is aimed toward large scale systems that even span organizational boundaries. In this paper we investigate the different techniques of fault tolerance which are used in many real time distributed systems. The main focus is on types of fault occurring in the system, fault detection techniques and the recovery techniques used. A fault can occur due to link failure, resource failure or by any other reason is to be tolerated for working the system smoothly and accurately. These faults can be detected and recovered by many techniques used accordingly. An appropriate fault detector can avoid loss due to system crash and reliable fault tolerance technique can save from system failure. This paper provides how these methods are applied to detect and tolerate faults from various Real Time Distributed Systems. The advantages of utilizing the check pointing functionality are obvious; however so far the Grid community has notdeveloped a widely accepted standard that would allow the Gridenvironment to consciously utilize low level check pointing packages.Therefore, such a standard named Grid Check pointing Architecture isbeing designed. The fault tolerance mechanism used here sets the jobcheckpoints based on the resource failure rate. If resource failureoccurs, the job is restarted from its last successful state using acheckpoint file from another grid resource. A critical aspect for anautomatic recovery is the availability of checkpoint files. A strategy to increase the availability of checkpoints is replication. Grid is a form distributed computing mainly to virtualizes and utilize geographically distributed idle resources. A grid is a distributed computational and storage environment often composed of heterogeneous autonomously managed subsystems. As a result varying resource availability becomes common place, often resulting in loss and delay of executing jobs. To ensure good performance fault tolerance should be taken into account. Here we address the fault tolerance in terms of resource failure. Commonly utilized techniques to achieve fault tolerance is periodic check pointing, which periodically saves the jobs state. But an inappropriate check pointing interval leads to delay in the job execution, and reduces the throughput. Hence in the proposed work, the strategy used to achieve fault tolerance is by dynamicall
Reverse Engineering of the Spindle Assembly Checkpoint  [PDF]
Andreas Doncic, Eshel Ben-Jacob, Shmuel Einav, Naama Barkai
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006495
Abstract: The Spindle Assembly Checkpoint (SAC) is an intracellular mechanism that ensures proper chromosome segregation. By inhibiting Cdc20, a co-factor of the Anaphase Promoting Complex (APC), the checkpoint arrests the cell cycle until all chromosomes are properly attached to the mitotic spindle. Inhibition of Cdc20 is mediated by a conserved network of interacting proteins. The individual functions of these proteins are well characterized, but understanding of their integrated function is still rudimentary. We here describe our attempts to reverse-engineer the SAC network based on gene deletion phenotypes. We begun by formulating a general model of the SAC which enables us to predict the rate of chromosomal missegregation for any putative set of interactions between the SAC proteins. Next the missegregation rates of seven yeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactions that correctly predicted the observed missegregation rates of all deletion mutants. Remarkably, although based on only seven phenotypes, the consistent network we obtained successfully reproduces many of the known properties of the SAC. Further insights provided by our analysis are discussed.
Role of the Checkpoint Clamp in DNA Damage Response  [PDF]
Mihoko Kai
Biomolecules , 2013, DOI: 10.3390/biom3010075
Abstract: DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen)-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR).
TLR4 and TLR9 Expression in Different Phenotypes of Rhinitis  [PDF]
Maria Lauriello,Alessandra Micera,Paola Muzi,Lino Di Rienzo Businco,Sergio Bonini
International Journal of Otolaryngology , 2012, DOI: 10.1155/2012/925164
Abstract: Background. Toll-like receptors (TLRs) represent a family of evolutionarily conserved proteins, that represent a fundamental link between innate and adaptive immune responses. Aim. The purpose of this study was to investigate the expression of TLR4 and TLR9 in the normal nasal mucosa and in the mucosa of subjects with different phenotypes of rhinitis. Methodology. A confocal analysis of TLR4 and TLR9 (co)expression was carried out on biopsies from the inferior turbinate obtained from 4 patients affected by persistent allergic rhinitis, 8 patients with chronic rhino-sinusitis, and 6 patients with vasomotor rhinitis The results were compared with those of specimens obtained from 4 subjects undergoing nasal surgery, but with signs of nasal inflammation. Results. TLR4 and TLR9 were expressed in the healthy nasal mucosa; TLR4 and TLR9 expression was significantly decreased in allergic rhinitis. TLR4 was over expressed in the epithelium of chronic rhino-sinusitis. Both TLRs were co-expressed in the sub-epithelial infiltrate of chronic and vasomotor rhinitis, even though this expression was higher in the former compared with the latter. Conclusions. This study indicates that TLR4 and TLR9 show a different pattern of expression in different phenotypes of rhinitis, possibly related to the type and severity of the disease.
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